Integrated operation of distribution grids for multiple energy carriers promises hitherto unused synergies in terms of efficient generation, storage, and consumption. A major obstacle to the ...investment in such systems is their increased complexity, as conventional tools and methods were not designed to capture all relevant technical and economic aspects of hybrid grids. To address this obstacle, this work proposes a methodology to systematically assess multi-carrier energy grids under a holistic scope. By adopting a simulation-based approach that relies on detailed technical and economic models, an efficient and precise evaluation of both short-term (operational) and long-term (strategic) aspects is supported. The methodology enables the assessment of system configurations, control strategies, business models, and regulatory conditions in one coherent approach. As a proof-of-concept, the new methodology is applied to a real-world use case of a hybrid thermal-electrical distribution grid in a central European city. The results are comprehensively discussed to showcase how the various aspects of hybrid energy systems are addressed. The outcomes also demonstrate how this methodology aids the involved stakeholders in understanding the associated risks and potentials, paving the way for early adopters to realize multi-carrier energy distribution grids.
•A holistic methodology to study multi-carrier energy systems is presented.•Operational technical and strategic economic perspectives are considered.•Established tools for different domains are coupled in a co-simulation framework.•Multiple market participants and opposing objectives are taken into account.•The methodology is demonstrated by a comprehensive study in a central European city.
We present two case studies on energy grid hybridization, where the distribution networks of multiple energy sectors are more tightly coupled together to increase their flexibility via mutual ...transfer of energy. The hybridization approaches were developed in cooperation with the local stakeholder in a northern European city, comprising of a short-term setup with a low adoption barrier as well as a long-term scenario with more involved grid coupling using more efficient devices. For a range of coupling device configurations, device locations, control algorithms, and assumptions on utility prices and energy demand, we investigate the influence of the hybridization on the energy mix, CO 2 emissions, and energy costs. The studies have been conducted using a co-simulation toolchain developed by the European Project OrPHEuS specifically for fine-grained technical simulation of multi-carrier grids. Our results confirm that the hybrid grid approach is an effective means to increase the share of renewable energies and reduce operational costs. It also turns out that precise forecasts of energy demand and utility prices are essential for appropriate dimensioning of the coupling points.
•DAVA pretreatment increases the survival rate against APAP overdose-induced mortality.•DAVA pretreatment inhibits necrosis and ROS formation in the liver.•DAVA pretreatment blocks depletion of GSH ...and ATP in the liver.•DAVA pretreatment down-regulates JNK and ERK activations.•DAVA has treatment effect against APAP overdose-induced hepatotoxicity as well.
Oxidative stress is closely associated with acetaminophen (APAP)-induced toxicity. Davallialactone (DAVA), a hispidin analog derived from the mushroom Inonotus xeranticus, has antioxidant properties. This study evaluated whether DAVA plays protective roles against APAP hepatotoxicity in mice. Pretreatments with DAVA (10mg/kg) prior to exposures of mice to a hepatotoxic dose of 600mg/kg APAP significantly increased survival rate compared to APAP alone. To verify this effect, mice were treated with 400mg/kg APAP 30min after DAVA administration and were then sacrificed after 0.5, 1, 3, and 6h. APAP alone caused severe liver injuries as characterized by increased plasma GOT and GPT levels, ATP and GSH depletion, and peroxynitrite and 4-HNE formations. These liver damages induced by APAP were significantly attenuated by DAVA pretreatments. The GSH/GSSG ratio nearly recovered to the levels observed in non-APAP-treated mice at 6h after APAP treatment in DAVA-pretreated mice. Furthermore, while hepatic ROS levels were increased by APAP exposures, pretreatments with DAVA completely blocked ROS formation. In addition, APAP-induced sustained activations of JNK and ERK were remarkably reduced by DAVA pretreatment. In conclusion, these results suggest that DAVA plays protective roles against APAP-mediated hepatotoxicity through function as ROS scavenger.
Aims
Hypertension is one of the most common human diseases worldwide, and extensive research efforts are focused upon the identification and utilizing of novel therapeutic drug targets. Nitric oxide ...(NO) produced by endothelial NO synthase (eNOS) is an important regulator of blood pressure (BP). β-Lapachone (βL), a well-known substrate of NAD(P)H:quinone oxidoreductase (NQO1), increases the cellular NAD+/NADH ratio via the activation of NQO1. In this study, we evaluated whether βL-induced activation of NQO1 modulates BP in an animal model of hypertension.
Methods and results
Spontaneously hypertensive rats (SHR), primary human aortic endothelial cells (HAEC), and endothelial cell lines were used to investigate the hypotensive effect of βL and its mode of action. βL treatment stimulated endothelium-dependent vascular relaxation in response to acetylcholine in aorta of SHR and dramatically lowered BP in SHR, but the hypotensive effect was completely blocked by eNOS inhibition with ω-nitro-l-arginine methyl ester. Aortic eNOS phosphorylation and eNOS protein expression were significantly increased in βL-treated SHR. In vitro studies revealed that βL treatment elevated the intracellular NAD+/NADH ratio and concentration of free Ca2+ (Ca2+i), and resulted in Akt/AMP-activated protein kinase/eNOS activation. These effects were abolished by NQO1 siRNA and Ca2+i inhibition through a ryanodine receptor blockade.
Conclusion
This study is the first to demonstrate that NQO1 activation has a hypotensive effect mediated by eNOS activation via cellular NAD+/NADH ratio modulation in an animal model. These results provide strong evidence suggesting NQO1 might be a new therapeutic target for hypertension.
Platycodon grandiflorum (PG) (Korean name, Doraji; Chinese name, Jiegeng; and Japanese name, Kikyo) is a perennial plant in the Campanulaceae family that contains triterpenoid saponins, ...carbohydrates, and fibers. This study was carried out to investigate effects of root of PG on fatty liver inhibition in high fat diet (HFD)-fed C57BL/6 mice. C57BL/6 mice were divided into control, total extract of PG (T-PG, 500 mg/kg) and saponin fraction (S-PG, 50 mg/kg)-treated groups. Significant decreases in body weight, associated with fat mass reduction, were observed in PG-treated groups (p<0.05). Hepatic lipid content and score index calculated from morphometric observations on fatty liver were significantly decreased in the PG-treated groups (p<0.05). Moreover, activities of fatty acid synthase (FAS) and carnitine palmitoyl-transferase (CPT) were significantly suppressed and increased as compared with the control group, respectively (p<0.05). mRNA expressions of the sterol regulatory element binding protein (SREBP1c) and stearoyl-CoA desaturase (SCD1) gene were suppressed in the T-PG and S-PG groups (p<0.05). From these findings, we speculate that fatty liver inhibition effects of PG extract and its saponins appear to be conferred by hepatic lipogenesis and acceleration of energy expenditure, along with modulation of liver FAS and CPT activities in HFD-fed C57BL/6 mice.
•Cisplatin-induced ROS production leads to NOQ1 expression.•NQO1−/− mice showed increased mortality and enhanced susceptibility on cisplatin induced renal injury.•Genetic deletion of NQO1 accelerates ...cisplatin-induced histopathological damage in the kidney.•NOQ1 competes with NADPH oxidase.•Pharmacological activation of NOQ1 attenuates cisplatin-induced renal failure.
Although cisplatin is widely used as an anti-cancer agent, its use is significantly limited because of its tendency to induce nephrotoxicity through poorly understood mechanisms. NAD(P)H:quinone oxidoreductase 1 (NQO1) is well known to regulate ROS generation. The purpose of this study was to investigate whether NQO1 modulates cisplatin-induced renal failure associated with NADPH oxidase (NOX)-derived ROS production in an animal model. NQO1−/− mice were treated with cisplatin (18mg/kg) and renal function, oxidative stress, and tubular apoptosis were assessed. NQO1−/− mice showed increased blood urea nitrogen and creatinine levels, tubular damage, oxidative stress, and apoptosis. In accordance with these results, the cellular NADPH/NADP ratio and NOX activity were markedly increased in the kidneys of NQO1−/− mice compared to NQO1+/+ mice. In addition, activation of NQO1 by βL treatment significantly improved renal dysfunction and reduced tubular cell damage, oxidative stress, and apoptosis. This study demonstrates that NQO1 protects cells against renal failure induced by cisplatin, and that this effect is mediated by decreased NOX activity via cellular NADPH/NADP modulation. These results provide convincing evidence that NQO1 might be beneficial for ameliorating renal failure induced by cisplatin.
Ischemia/reperfusion (I/R) is the most common cause of acute renal injury. I/R-induced reactive oxygen species (ROS) are thought to be a major factor in the development of acute renal injury by ...promoting the initial tubular damage. NAD(P)H:quinone oxidoreductase 1 (NQO1) is a well-known antioxidant protein that regulates ROS generation. The purpose of this study was to investigate whether NQO1 modulates the renal I/R injury (IRI) associated with NADPH oxidase (NOX)-derived ROS production in an animal model. We analyzed renal function, oxidative stress, and tubular apoptosis after IRI. NQO1−/− mice showed increased blood urea nitrogen and creatinine levels, tubular damage, oxidative stress, and apoptosis. In the kidneys of NQO1−/− mice, the cellular NADPH/NADP+ ratio was significantly higher and NOX activity was markedly higher than in those of NQO1+/+ mice. The activation of NQO1 by β-lapachone (βL) significantly improved renal dysfunction and reduced tubular cell damage, oxidative stress, and apoptosis by renal I/R. Moreover, the βL treatment significantly lowered the cellular NADPH/NADP+ ratio and dramatically reduced NOX activity in the kidneys after IRI. From these results, it was concluded that NQO1 has a protective role against renal injury induced by I/R and that this effect appears to be mediated by decreased NOX activity via cellular NADPH/NADP+ modulation. These results provide convincing evidence that NQO1 activation might be beneficial for ameliorating renal injury induced by I/R.
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•Ischemia/reperfusion-induced ROS production leads to NQO1 expression.•NQO1−/− mice show increased enhanced susceptibility to ischemia/reperfusion-induced acute renal injury.•Genetic deletion of NQO1 accelerates ischemia/reperfusion-induced renal function and histopathological damage in the kidney.•NQO1 competes with NADPH oxidase.•Pharmacological activation of NQO1 attenuates ischemia/reperfusion-induced acute renal failure.
Abstract Although the safety of gold nanoparticle (AuNP) use is of growing concern, most toxicity studies of AuNPs had focused on their chemical characteristics, including their physical dimensions, ...surface chemistry, and shape. The present study examined the susceptibility of rodents with healthy or damaged livers to AuNP-induced hepatotoxicity. To induce a model of liver injury, mice were fed a methionine- and choline-deficient (MCD) diet for 4 weeks. Sizes and biodistribution of 15-nm PEGylated AuNPs were analyzed by transmission electron microscopy. Levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were estimated with an automatic chemical analyzer, and liver sections were subjected to pathological examination. Activities of antioxidant enzymes were determined by biochemical assay. Lateral tail vein injection of MCD diet-fed mice with 5 mg kg−1 AuNPs significantly elevated the serum ALT and AST levels compared to MCD diet-fed mice injected with mPEG (methylpolyethylene glycol). Similarly, severe hepatic cell damage, acute inflammation, and increased apoptosis and reactive oxygen species (ROS) production were observed in the livers of AuNP-injected mice on the MCD diet; these liver injuries were attenuated in mice fed a normal chow diet. The results suggest that AuNPs display toxicity in a stressed liver environment by stimulating the inflammatory response and accelerating stress-induced apoptosis. These conclusions may point to the importance of considering health conditions, including liver damage, in medical applications of AuNPs.
•Scoparone decreases triglyceride accumulation in 3T3-L1 preadipocytes.•Scoparone suppressed mRNA expression of adipogenic transcription factors and enzymes.•Scoparone negatively regulates the ...transcriptional activity of PPARγ.•Scoparone strongly inhibited binding of PPARγ to PPRE region.
This study was performed to investigate the effect of scoparone on the differentiation of 3T3-L1 preadipocytes. Scoparone inhibited triglyceride (TG) accumulation in the mature adipocytes, evidenced by Oil-red O staining and intracellular quantification. Real time-PCR analysis showed that scoparone significantly down-regulated the mRNA expression of key adipogenic transcription factors, PPARγ, C/EBPα, compared with mature adipocytes. Scoparone appeared to reduce mRNA expression of SREBP1c and FAS being related to the late stage of adipogenesis. Furthermore, aP2 and CD36/FAT, as adipocyte-specific genes, were decreased in mature adipocytes by scoparone treatment. Moreover, scoparone inhibited the up-regulated expression of PPARγ target genes by rosiglitazone to near that observed in cells treated with GW9662. The luciferase assay revealed that scoparone negatively regulates the transcriptional activity of PPARγ. Chromatin immunoprecipitation assay also showed that participation of scoparone in the regulation of PPARγ. Collectively, scoparone has a PPARγ antagonic effect and suppresses differentiation through down-regulation of adipogenic genes by PPARγ inhibition in 3T3-L1 preadipocytes.
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