Systems-Level Feedbacks of NRF2 Controlling Autophagy upon Oxidative Stress Response

Although the primary role of autophagy-dependent cellular self-eating is cytoprotective upon various stress events (such as starvation, oxidative stress, and high temperatures), sustained autophagy might lead to cell death. A transcription factor called NRF2 (nuclear factor erythroid-related factor 2) seems to be essential in maintaining cellular homeostasis in the presence of either reactive oxygen or nitrogen species generated by internal metabolism or external exposure. Accumulating experimental evidence reveals that oxidative stress also influences the balance of the 5′ AMP-activated protein kinase (AMPK)/rapamycin (mammalian kinase target of rapamycin or mTOR) signaling pathway, thereby inducing autophagy. Based on computational modeling here we propose that the regulatory triangle of AMPK, NRF2 and mTOR guaranties a precise oxidative stress response mechanism comprising of autophagy. We suggest that under conditions of oxidative stress, AMPK is crucial for autophagy induction via mTOR down-regulation, while NRF2 fine-tunes the process of autophagy according to the level of oxidative stress. We claim that the cellular oxidative stress response mechanism achieves an incoherently amplified negative feedback loop involving NRF2, mTOR and AMPK. The mTOR-NRF2 double negative feedback generates bistability, supporting the proper separation of two alternative steady states, called autophagy-dependent survival (at low stress) and cell death (at high stress). In addition, an AMPK-mTOR-NRF2 negative feedback loop suggests an oscillatory characteristic of autophagy upon prolonged intermediate levels of oxidative stress, resulting in new rounds of autophagy stimulation until the stress events cannot be dissolved. Our results indicate that AMPK-, NRF2- and mTOR-controlled autophagy induction provides a dynamic adaptation to altering environmental conditions, assuming their new frontier in biomedicine

Effects of enzyme treatment of the microfiltration of elderberry

The aim of this study was to evaluate the effect of microfiltration (MF) on the antioxidant capacity of elderberry juice using ceramic membrane. Previous to MF measurements preliminary examination was achieved with different enzymes. Four different samples were prepared: one without any enzyme and three with different pectolytic enzymes. The resistances were determined using the resistance-in-series model and difference between four enzyme-treated samples are evaluated. The effect of this technology on the antioxidant component of the clarified elderberry juice has been evaluated in permeate and retentate samples. For ferric reducing antioxidant power was measured with FRAP and total phenolic content (TPC) was determined with Folin Ciocalteau reagent. The total anthocyanin content (TAC) was estimated using spectrophotometric method. Higher juice yield was obtained using enzyme compared with enzyme-free elderberry pulp. The analytical results show that the MF membrane retained the valuable components in different rate. Significant losses are believed to have occurred after the MF clarification process due to fouling layer resistance, what can be decreased with pectolytic enzymes treatment

Acute 5-HT 2C Receptor Antagonist SB-242084 Treatment Affects EEG Gamma Band Activity Similarly to Chronic Escitalopram

Serotonin 2C receptors (5-HT2CRs) are implicated in the pathomechanism and treatment of anxiety and depression. Recently, as a new biomarker of depression, alterations in the gamma power of the electroencephalogram (EEG) have been suggested. Chronic treatment with the selective serotonin reuptake inhibitor (SSRI) antidepressant escitalopram has been shown to cause sleep-wake stage-dependent alterations in gamma power. However, despite the antidepressant potency of 5-HT2CR-antagonists, there is no data available regarding the effects of selective 5-HT2CR-antagonists on gamma activity. Therefore, we investigate the acute effect of the 5-HT2CR-antagonist SB-242084 on gamma power in different vigilance stages when given in monotherapy, or in combination with chronic escitalopram treatment. We administered SB-242084 (1 mg/kg, intraperitoneally) or vehicle to EEG-equipped rats after a 21-day-long pretreatment with escitalopram (10 mg/kg/day, via osmotic minipumps) or vehicle. Frontoparietal EEG, electromyogram, and motor activity were recorded during the first 3 h of passive phase, after the administration of SB-242084. Quantitative EEG analysis revealed that acute SB-242084 increased gamma power (30–60 Hz) in light and deep slow-wave sleep, and passive wakefulness. However, in active wakefulness, rapid eye movement sleep, and intermediate stage, no change was observed in gamma power. The profile of the effect of SB-242084 on gamma power was similar to that produced by chronic escitalopram. Moreover, SB-242084 did not alter chronic escitalopram-induced effects on gamma. In conclusion, the similarity in the effect of the 5-HT2CR-antagonist and chronic SSRI on gamma power provides further evidence for the therapeutic potential of 5-HT2CR-antagonists in the treatment of depression and/or anxiety

Effects of Enzyme Treatment on the Microfiltration of Elderberry

The aim of this study was to evaluate the effect of microfiltration (MF) on the antioxidant capacity of elderberry juice using ceramic membrane. Previous to MF measurements preliminary examination was achieved with different enzymes. Four different samples were prepared: one without any enzyme and three with different pectolytic enzymes. The resistances were determined using the resistance-in-series model and difference between four enzyme-treated samples are evaluated. The effect of this technology on the antioxidant component of the clarified elderberry juice has been evaluated in permeate and retentate samples. For ferric reducing antioxidant power was measured with FRAP and total phenolic content (TPC) was determined with Folin Ciocalteau reagent. The total anthocyanin content (TAC) was estimated using spectrophotometric method. Higher juice yield was obtained using enzyme compared with enzyme-free elderberry pulp. The analytical results show that the MF membrane retained the valuable components in different rate. Significant losses are believed to have occurred after the MF clarification process due to fouling layer resistance, what can be decreased with pectolytic enzymes treatment

NRF2-ome: An integrated web resource to discover protein interaction and regulatory networks of NRF2

NRF2 is the master transcriptional regulator of oxidative and xenobiotic stress responses. NRF2 has important roles in carcinogenesis, inflammation, and neurodegenerative diseases. We developed an online resource, NRF2-ome, to provide an integrated and systems-level database for NRF2. The database contains manually curated and predicted interactions of NRF2 as well as data from external interaction databases. We integrated NRF2 interactome with NRF2 target genes, NRF2 regulating TFs, and miRNAs. We connected NRF2-ome to signaling pathways to allow mapping upstream NRF2 regulatory components that could directly or indirectly influence NRF2 activity totaling 35,967 protein-protein and signaling interactions. The user-friendly website allows researchers without computational background to search, browse, and download the database. The database can be downloaded in SQL, CSV, BioPAX, SBML, PSI-MI, and in a Cytoscape CYS file formats. We illustrated the applicability of the website by suggesting a posttranscriptional negative feedback of NRF2 by MAFG protein and raised the possibility of a connection between NRF2 and the JAK/STAT pathway through STAT1 and STAT3. NRF2-ome can also be used as an evaluation tool to help researchers and drug developers to understand the hidden regulatory mechanisms in the complex network of NRF2. © 2013 Dénes Türei et al

Possibilities of complex food-processing of quince

The food industry generate large amount of such by-products, which may also contain unused, valuable components. In this research the possibilities of complex food industry usability were investigated for three species of quince (Cydonia oblonga Mill.) (“Angersi, Bereczki, Konstantinápolyi”). The nutritional characteristics of quince skin, pulp and ovary were compered. We measured the nutritional properties: dry matter content, pectin and acid content, polyphenol and flavonoid content. Moreover the rheological properties were investigated. The results were analyzed with statistics method. The results of dry content are not significant, but between samples of quince parts the pectin and acid content have significant difference. It was largest amount of polyphenol in the pulp of quince, and the most of flavonoid content were measured in the skin of quince. Concluding from the rheological properties ‘Angersi’ species are suggested to use as jam, quince jelly or natural texturing, while ‘Konstantinápolyi’ species are recommended to use for the production of fiber juices or syrups. Because of theirs high pectin content, the skin and ovary suitable to use as production of pectin or natural texturing. Due to high antioxidant capacity of skin and ovary may use at manufacture of natural antimicrobial agents, dietary supplements or functional food

Analysis of the antioxidant properties of sea buckthorn jams during storage

In the frame of this research, sea buckthorn jams were prepared by blending sea buckthorn pulp with apple pomace powder in varying proportions to achieve especially good organoleptic characteristics and texture without the addition of pectin. Apple pomace is a byproduct of apple juice production, and it might be suitable for replacing pectin in jam products. Sea buckthorn is an excellent ingredient of functional foods, having outstandingly useful biologically active compounds. It has positive impact on human health primarily as a result of its high C-vitamin, flavonoid, and carotenoid content. In this study, we compared the following quality parameters of sea buckthorn jam samples: water soluble dry matter content, titratable acid, polyphenol contents, antioxidant activity, and carotenoid components. Sea buckthorn jams were prepared from ‘Leikora’ berries by adding different proportions of apple pomace (0, 0.5, 1, 1.5, 2%). One jam was prepared for being used as control by adding pectin. Determination of dry mater content was fulfilled based on Codex Alimentarius 3-1-558/93 formula. Total titratable acid content was determined based on MSZ EN Nr 12147:1998 Hungarian Standard. Antioxidant status was determined by Ferric Reducing Antioxidant power (FRAP) assay and total polyphenol content using spectrophotometer; with high performance liquid chromatography (HPLC) β carotenoid was also identified and quantified. Consumer panel testing of the jams was carried out by sensory testing. Significant differences were shown in the quality parameters of sea buckthorn jams. Increasing the amount of apple pomace added to the sea buckthorn -apple jams resulted in higher polyphenol content of the samples. The loss of polyphenols was decreasing during storage, the more apple pomace was added to the samples. Adding apple pomace, was also favorable as it lowered the loss of β carotenoid during storage. Increasing the pomace proportion resulted in higher antioxidant capacity; however, the more apple pomace was added, the antioxidant capacity was decreasing in a higher degree during storage. The pomace did not have any negative effect on the sensory attributes, but it favorably affected the changes of valuable components during the storage; thus it might be a suitable replacement of pectin

Zöldségalapú probiotikus készítmények egészségvédő komponenseinek vizsgálata

Napjainkban a funkcionális élelmiszer kifejezés egyre nagyobb teret hódít, azonban szervezetünk számára szükséges probiotikumok bevitele nem minden ember számára történhet azonos úton. Azok számára, akik laktózintoleranciával vagy tejcukor érzékenységgel élnek együtt, a tej alapú probiotikus készítmények fogyasztása nem egy járható út, így számukra alternatív megoldást kell biztosítani. Kísérletünk során három kereskedelmi forgalomban kapható zöldséglevet (paradicsomlé, sárgarépalé, céklalé) vizsgáltunk, melyek mindegyikét probiotikus Bifidobacterium lactis Bb-12 törzzsel oltottunk be, majd 3 hetes tárolási kísérlet alatt vizsgáltuk az antioxidáns hatású vegyületek mennyiségét három különböző módszerrel. Mértük a polifenol tartalmát (TPC), troloxra vonatkoztatott (TEAC) és vasredukálóképességen alapuló (FRAP) antioxidáns kapacitását. Az eredmények kiértékelése után megállapítható, hogy a vizsgált módszerekkel a legtöbb esetben az antioxidáns hatású összetevőkben nem mutatható ki szignifikáns változás a fermentálást követően, valamint a céklalé kiemelkedően nagy mennyiségű antioxidáns tulajdonságú komponenseket tartalmaz, melyet a fermentálás után kisebb csökkenést mutatva, de továbbra is jelentős mennyiségben őriz meg