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Mineralocorticoid receptor (MR) overactivation promotes cardiac fibrosis. We studied the ability of the non-steroidal MR antagonist finerenone to prevent fibrotic remodeling. In ...neonatal rat cardiac fibroblasts, finerenone prevented aldosterone-induced nuclear MR translocation. Treatment with finerenone decreased the expression of connective tissue growth factor (CTGF) (74 ± 15% of control, p = 0.005) and prevented aldosterone-induced upregulation of CTGF and lysyl oxidase (LOX) completely. Finerenone attenuated the upregulation of transforming growth factor ß (TGF-ß), which was induced by the Rac1 GTPase activator l-buthionine sulfoximine. Transgenic mice with cardiac-specific overexpression of Rac1 (RacET) showed increased left ventricular (LV) end-diastolic (63.7 ± 8.0 vs. 93.8 ± 25.6 µl, p = 0.027) and end-systolic (28.0 ± 4.0 vs. 49.5 ± 16.7 µl, p = 0.014) volumes compared to wild-type FVBN control mice. Treatment of RacET mice with 100 ppm finerenone over 5 months prevented LV dilatation. Systolic and diastolic LV function did not differ between the three groups. RacET mice exhibited overactivation of MR and 11ß hydroxysteroid dehydrogenase type 2. Both effects were reduced by finerenone (reduction about 36%, p = 0.030, and 40%, p = 0.032, respectively). RacET mice demonstrated overexpression of TGF-ß, CTGF, LOX, osteopontin as well as collagen and myocardial fibrosis in the left ventricle. In contrast, expression of these parameters did not differ between finerenone-treated RacET and control mice. Finerenone prevented left atrial dilatation (6.4 ± 1.5 vs. 4.7 ± 1.4 mg, p = 0.004) and left atrial fibrosis (17.8 ± 3.1 vs. 12.8 ± 3.1%, p = 0.046) compared to vehicle-treated RacET mice. In summary, finerenone prevented from MR-mediated structural remodeling in cardiac fibroblasts and in RacET mice. These data demonstrate anti-fibrotic myocardial effects of finerenone.
The aim of the study was to characterize the role of Rac1 GTPase for the mineralocorticoid receptor (MR)-mediated pro-fibrotic remodeling. Transgenic mice with cardiac overexpression of ...constitutively active Rac1 (RacET) develop an age-dependent phenotype with atrial dilatation, fibrosis, and atrial fibrillation. Expression of MR was similar in RacET and WT mice. The expression of 11β hydroxysteroid dehydrogenase type 2 (11β-HSD2) was age-dependently up-regulated in the atria and the left ventricles of RacET mice on mRNA and protein levels. Statin treatment inhibiting Rac1 geranylgeranylation reduced 11β-HSD2 up-regulation. Samples of human left atrial myocardium showed a positive correlation between Rac1 activity and 11β-HSD2 expression (r = 0.7169). Immunoprecipitation showed enhanced Rac1-bound 11β-HSD2 relative to Rac1 expression in RacET mice that was diminished with statin treatment. Both basal and phorbol 12-myristate 13-acetate (PMA)-induced NADPH oxidase activity were increased in RacET and correlated positively with 11β-HSD2 expression (r = 0.788 and r = 0.843, respectively). In cultured H9c2 cardiomyocytes, Rac1 activation with l-buthionine sulfoximine increased; Rac1 inhibition with NSC23766 decreased 11β-HSD2 mRNA and protein expression. Connective tissue growth factor (CTGF) up-regulation induced by aldosterone was prevented with NSC23766. Cardiomyocyte transfection with 11β-HSD2 siRNA abolished the aldosterone-induced CTGF up-regulation. Aldosterone-stimulated MR nuclear translocation was blocked by the 11β-HSD2 inhibitor carbenoxolone. In cardiac fibroblasts, nuclear MR translocation induced by aldosterone was inhibited with NSC23766 and spironolactone. NSC23766 prevented the aldosterone-induced proliferation and migration of cardiac fibroblasts and the up-regulation of CTGF and fibronectin. In conclusion, Rac1 GTPase regulates 11β-HSD2 expression, MR activation, and MR-mediated pro-fibrotic signaling.
Developing a hydrogen peroxide (H
2
O
2
) sensor able to measure small concentrations of H
2
O
2
in-situ
is crucial to understanding the degradation mechanisms that take place in the ...Membrane-Electrode-Assembly of a PEM-fuel cell. Fiber optic sensing probes based on Prussian blue (PB) are promising for this application. The PB film is however required to sustain the harsh environment of PEM-fuel cells. In this work, Prussian blue films have been deposited at different synthesis temperatures, and using different precursors. The samples were immersed and left in a Phosphate-Buffer-Solution (PBS) at pH 2 at 80 °C for 21 hours and thereafter at 90 °C for 3 hours. These PB films were characterized using FTIR to analyze their stability following PBS processing at operating temperature and pH corresponding to an operating PEM-fuel cell. The PB film prepared using the single-source-precursor (SSP) at the temperature of 60 °C is found to be the most stable.
Developing a hydrogen peroxide (H2O2) sensor able to measure small concentrations of H2O2 in-situ is crucial to understanding the degradation mechanisms that take place in the ...Membrane-Electrode-Assembly of a PEM-fuel cell. Fiber optic sensing probes based on Prussian blue (PB) are promising for this application. The PB film is however required to sustain the harsh environment of PEM-fuel cells. In this work, Prussian blue films have been deposited at different synthesis temperatures, and using different precursors. The samples were immersed and left in a Phosphate-Buffer-Solution (PBS) at pH 2 at 80 °C for 21 hours and thereafter at 90 °C for 3 hours. These PB films were characterized using FTIR to analyze their stability following PBS processing at operating temperature and pH corresponding to an operating PEM-fuel cell. The PB film prepared using the single-source-precursor (SSP) at the temperature of 60 °C is found to be the most stable.
The electrochemistry and cytotoxicity of marcanine A were investigated by electrochemical, computational and cellular studies. To enable a structure-toxicity-relationship of the natural product, ...eleven novel synthetic derivatives with different electrochemical properties were synthesized and tested. Derivative
5
revealed a GI50 in the low μM range, being more active than the actual natural product. A clear correlation was found between the experimental and the calculated data.
The electrochemistry and cytotoxicity of marcanine A were investigated by electrochemical, computational and cellular studies.
A thien-2-yl substituted, electron-rich phenothiazine has been converted over several steps into a redox active sol-gel precursor. Following a fluoride-catalyzed synthesis, a phenothiazine-based ...mesoporous hybrid organosilica was obtained. The electrochemical behavior and the luminescence properties of the immobilized chromophore have been studied using solid state fluorescence spectroscopy, electron paramagnetic resonance spectroscopy (EPR) and solid state voltammetry (CV and DPV). The influence of both the presence of fluoride anions and the acidic pH during the material synthesis were explored by means of scanning and transmission electron microscopy (SEM and TEM), X-ray powder diffraction (XRD) and nitrogen physisorption measurements. While a combination of acidic pH and fluoride was found necessary for the material formation, partial cleavage of the precursor was observed. Data obtained from both the chemical as well as the electrochemical oxidation/reduction of the immobilized PT dye indicates the formation of an organic layer containing several species inside the pore channels.
The present work deals with testing procedures based on Fuel Cell Testing and Quality Assurance (FCTES
QA
) for Proton Exchange Membrane Fuel Cells (PEM FCs) stacks. Within these procedures ...parameters like pressure, temperature, humidification and stoichiometry have been varied. All this leads to optimized operating parameters to improve the efficiency of the stack. The optimization should lead to a more efficient Micro-combined heat and power (Micro-CHP) system with an integrated PEM FC stack. It is one of the most efficient principals for utilization of energy content of fuels, whether fossil or renewable. There are a lot of advantages for Micro-CHP systems like high overall efficiency, possible grid independency and flexibility in supply on demand. In any case, some research aspects must be taken into account, such as the complex gas purification, gas humidification, and the low temperature gradient for the heat exchangers in a heating system.
Abstract
Developing a suitable hydrogen peroxide (H
2
O
2
) sensor able to measure small concentrations of H
2
O
2
in-operando within a fuel cell is crucial to understanding the degradation ...mechanisms that take place in a Membrane-Electrode-Assembly of a PEM-fuel cell. Recently, fiber optic sensing probes based on Prussian blue (PB) have shown reliable response to H
2
O
2
concentrations 1, 2, paving the way for further investigation inside operating PEM-fuel cells. This requires deposition of a robust PB film able to sustain the harsh environment of PEM-fuel cells. In this work, Prussian blue films have been deposited at different synthesis temperatures, and using different precursors including potassium ferrocyanide, potassium ferricyanide, iron chloride (III), and tetraethyl orthosilicate. The samples were immersed and left in a Phosphate Buffer Solution (PBS) of pH 2 at 80 °C for 21 hours and, in thereafter at 90 °C for 3 hours. These PB films were characterized using Fourier Transform Infrared Spectroscopy to analyze their adhesion properties following PBS processing at operating temperature and pH corresponding to an operating PEM-fuel cell.
Experimental
PB films were deposited on microscopic glass slides using three different processes including; (a) the sol-gel process and dip coating technique, (b) chemical deposition of PB using potassium ferrocyanide and iron chloride (III), and (c) single-source-precursor deposition of PB using potassium ferricyanide. All three processes were performed in an aqueous solution of 0.1 mol L
-1
hydrochloric acid at 60 °C and the prepared samples were dried first at room temperature and then at 100 °C for 15 min.
To study the effect of synthesis temperature on adhesion properties of PB films, several more samples were prepared through the single-source-precursor route at temperatures of 40 °C, 60 °C, and 80 °C.
Two samples were prepared under each condition, with one sample subjected to PBS processing and followed by characterization of both samples using FTIR to study the effect of deposition process and synthesis temperature on adhesion properties of PB films.
Results and Discussion
Fig. 1 shows the FTIR spectra of the samples synthesized through different processes before (red lines) and after (blue lines) PBS processing in the range of 2500 cm
-1
to 1500 cm
-1
. The peak at 2083 cm
-1
is the characteristic absorption peak of PB which is assigned as the stretching vibration of C≡N group in PB structure 3. The sample prepared through the third process, (PB (III)) has the strongest peak at 2083 cm
-1
both before and after PBS processing, indicating that the most stable and thickest PB film were prepared through this process. Conversely, the samples prepared through the first process (PB-Silica) exhibits the weakest peak at 2083 cm
-1
before PBS processing and almost no characteristic peak after PBS processing which means the PB film was completely leached into the PBS. Also, the sample which was prepared through the second process, (PB (II)) does not suffer from complete leaching in PBS; however the characteristic peak of PB at 2083 cm
-1
is not as strong as the peak for the third process (PB (III)). We conclude that less PB is deposited onto the substrate through the second process (PB (II)) compared to the third one (PB (III)).
Fig. 2 depicts the FTIR spectra in the range of 2500 cm
-1
to 1500 cm
-1
for the samples synthesized through the third process at different temperatures ranging from 40 °C to 80 °C. The red lines and blue lines are the spectra of the samples before and after PBS processing, respectively. The sample which was prepared at 40 °C does not have any distinct peak at 2083 cm
-1
after PBS processing which indicates the PB film was completely leached into PBS because of its poor adhesion properties. On the other hand, the PB films prepared at 60 °C and 80 °C have a strong peak at 2083 cm
-1
both before and after PBS processing which confirms the good adhesion properties of PB films prepared at these temperatures. Since there is no specific advantage between the PB films prepared at 60 °C and 80 °C, a temperature of 60 °C can be chosen as the optimum synthesis temperature to achieve the most stable PB film through this technique.
Acknowledgments
This work was supported by the German Academic Exchange Service (DAAD), and through a Strategic Research Grant from the Natural Science and Engineering Research Council (NSERC) of Canada.
References
1 Akbari Khorami et al., Electrochimica Acta 115 (2014) 416- 424.
2 Botero-Cadavid et al., Sensors and Actuators B: Chemical 185 (2013) 166-173.
3 Farah et al., Int. J. Electrochem. Sci 8 (2013) 12132-12146.
Figure 1
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