Various bioactive compounds (BCs) often possess poor stability and bioavailability, which makes it difficult for them to exert their potential health benefits. These limitations can be countered by ...the use of nano-delivery systems (NDSs), such as nanoparticles and nanoemulsions. NDSs can protect BCs against harsh environments during food processing and digestion, and thereby, could enhance the bioavailability of BCs. Although various NDSs have been successfully produced with both synthetic and natural materials, it is necessary to fulfill safety criteria in the delivery materials for food applications. Food-grade materials for the production of NDSs, such as milk proteins and carbohydrates, have received much attention due to their low toxicity, biodegradability, and biocompatibility. Among these, whey proteins-from whey, a byproduct of cheese manufacturing-have been considered as excellent delivery material because of their high nutritional value and various functional properties, such as binding capability to various compounds, gelation, emulsifying properties, and barrier effects. Since the functional and physicochemical properties of whey protein-based NDSs, including size and surface charge, can be key factors affecting the applications of NDSs in food, the objectives of this review are to discuss how manufacturing variables can modulate the functional and physicochemical properties of NDSs and bioavailability of encapsulated BCs to produce efficient NDSs for various BCs.
Common treatment modalities for non-small cell lung cancer (NSCLC) involve the EGF receptor-tyrosine kinase inhibitors (EGFR-TKIs) like gefitinib and erlotinib. However, the vast majority of treated ...patients acquire resistance to EGFR-TKIs, due, in large part, to secondary mutations in EGFR or amplification of the MET gene. Our purpose was to test ubiquitin-specific peptidase 8 (USP8) as a potential therapeutic target for gefitinib-resistant and -sensitive non-small cell lung cancer (NSCLC).
Testing the effect of knockdown of USP8 and use of a synthetic USP8 inhibitor to selectively kill gefitinib-resistant (or -sensitive) NSCLCs with little effect on normal cells in cell culture and a xenograft mouse model.
Knockdown of ubiquitin-specific peptidase 8 (USP8) selectively kills gefitinib-resistant NSCLCs while having little toxicity toward normal cells. Genetic silencing of USP8 led to the downregulation of several receptor tyrosine kinases (RTK) including EGFR, ERBB2, ERBB3, and MET. We also determined that a synthetic USP8 inhibitor markedly decreased the viability of gefitinib-resistant and -sensitive NSCLC cells by decreasing RTK expression while having no effect on normal cells. Moreover, treatment with a USP8 inhibitor led to significant reductions in tumor size in a mouse xenograft model using gefitinib-resistant and -sensitive NSCLC cells.
Our results show for the first time that the inhibition of USP8 activity or reduction in USP8 expression can selectively kill NSCLC cells. We propose USP8 as a potential therapeutic target for gefitinib-resistant and -sensitive NSCLC cells.
Glycyrrhizin is the major active component extracted from licorice (Glycyrrhiza glabra) roots, one of the most widely used herbal preparations for the treatment of liver disorders. This study ...evaluated the potential beneficial effect of glycyrrhizin in a mouse model of carbon tetrachloride (CCl4)-induced liver injury. The mice were treated intraperitoneally with CCl4 (0.5 ml/kg). They received glycyrrhizin (50, 100, 200, 400 mg/kg) 24 h and 0.5 h before and 4 h after administering CCl4. The serum activities of aminotransferase and the hepatic level of malondialdehyde were significantly higher 24 h after the CCl4 treatment, while the concentration of reduced glutathione was lower. These changes were attenuated by glycyrrhizin. CCl4 increased the level of circulating tumor necrosis factor-α markedly, which was reduced by glycyrrhizin. The levels of hepatic inducible nitric oxide synthase, cyclooxygenase-2, and heme oxygenase-1 protein expression were markedly higher after the CCl4 treatment. Glycyrrhizin diminished these alterations for inducible nitric oxide and cyclooxygenase-2 but the protein expression of heme oxygenase-1 was further elevated by the treatment of glycyrrhizin. CCl4 increased the level of tumor necrosis factor-α, inducible nitric oxide synthase, cyclooxygenase-2, and heme oxygenase-1 mRNA expressions. The mRNA expression of heme oxygenase-1 was augmented by the glycyrrhizin treatment, while glycyrrhizin attenuated the increase in tumor necrosis factor-α, inducible nitric oxide synthase, and cyclooxygenase-2 mRNA expressions. These results suggest that glycyrrhizin alleviates CCl4-induced liver injury, and this protection is likely due to the induction of heme oxygenase-1 and the downregulation of proinflammatory mediators.
Sepsis is a complex, multifactorial, rapidly progressive disease characterized by an overwhelming activation of the immune system and the countervailing antiinflammatory response. In the current ...study in murine peritoneal macrophages, chlorogenic acid suppressed endotoxin-induced high mobility group box 1 (HMGB1) release in a concentration-dependent manner. Administration of chlorogenic acid also attenuated systemic HMGB1 accumulation in vivo and prevented mortality induced by endotoxemia and polymicrobial sepsis. The mechanisms of action of chlorogenic acid included attenuation of the increase in toll-like receptor (TLR)-4 expression and suppression of sepsis-induced signaling pathways, such as c-Jun NH₂-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB, which are critical for cytokine release. The protection conferred by chlorogenic acid was achieved through modulation of cytokine and chemokine release, suppression of immune cell apoptosis and augmentation of bacterial elimination. Chlorogenic acid warrants further evaluation as a potential therapeutic agent for the treatment of sepsis and other potentially fatal systemic inflammatory disorders.
Forsythiae Fructus is known to have diuretic, anti-bacterial, and anti-inflammatory activities. This study examined the hepatoprotective effects of pinoresinol, a lignan isolated from Forsythiae ...Fructus, against carbon tetrachloride (CCl4 )–induced liver injury. Mice were treated intraperitoneally with vehicle or pinoresinol (25, 50, 100, and 200 mg/kg) 30 min before and 2 h after CCl4 (20μl/kg) injection. In the vehicle-treated CCl4 group, serum aminotransferase activities were significantly increased 24 h after CCl4 injection, and these increases were attenuated by pinoresinol at all doses. Hepatic glutathione contents were significantly decreased and lipid peroxidation was increased after CCl4 treatment. These changes were attenuated by 50 and 100 mg/kg of pinoresinol. The levels of protein and mRNA expression of inflammatory mediators, including tumor necrosis factor-α, inducible nitric oxide synthase, and cyclooxygenase-2, were significantly increased after CCl4 injection; and these increases were attenuated by pinoresinol. Nuclear translocation of nuclear factor-κB (NF-κB) and phosphorylation of c-Jun, one of the components of activating protein 1 (AP-1), were inhibited by pinoresinol. Our results suggest that pinoresinol ameliorates CCl4-induced acute liver injury, and this protection is likely due to antioxidative activity and down-regulation of inflammatory mediators through inhibition of NF-κB and AP-1.
The objectives of this research were to produce whey protein concentrate (WPC) multiple nanoemulsion (MNE) and to study how whey protein concentration level and antioxidant type affected the ...physicochemical properties and oxidative stability of fish oil in MNE. The morphological and physicochemical characteristics of MNE were investigated by using transmission electron microscopy and particle size analyzer, respectively. The oxidative stability of fish oil in MNEs was assessed by measuring peroxide value (PV), p‐anisidine value, and volatile compounds. The spherical forms of emulsions with size ranging from 190 to 210 nm were observed indicating the successful production of MNE. Compared with free fish oil, fish oil in MNE exhibited lower PV, p‐anisidine value, and formation of maker of oxidation of fish oil indicating the oxidative stability of fish oil in MNE was enhanced. PV, p‐anisidine value, and makers of oxidation of fish oil were decreased with increased WPC concentration level. The combined use of Vitamin C and E in MNE resulted in a reduction in PV and p‐anisidine value, and development of maker of oxidation. In conclusion, WPC concentration level and antioxidant type are key factors affecting the droplet size of MNE and oxidative stability of fish oil.
Recent studies have revealed that autophagy is induced under various disease conditions; however, the role of autophagy in pathological states is controversial.
quinone oxidoreductase 1 (NQO1) is a ...highly inducible cytoprotective gene that regulates reactive oxygen species (ROS) generation. In this study, we examined whether NQO1 deficiency affects the autophagy process in response to cisplatin-induced nephrotoxicity.
In vitro, NQO1 and autophagy-associated proteins were induced after cisplatin treatment and the autophagosomes markedly increased in the cisplatin-treated NQO1-knockdown ACHN cells together with increased ROS production. In vivo, NQO1-KO mice displayed a significant increase in cisplatin-induced acute kidney injury (AKI), as indicated by elevated tubular damage and apoptosis as well as by suppressed cytoprotective signals. In agreement with the in vitro findings, NQO1-KO cisplatin-treated mice displayed a notable increase in autophagy-associated protein expression compared with their wild-type counterparts. Meanwhile, the expression of Ras-related protein 7, which participates in autophagosome maturation and lysosome fusion, markedly decreased in NQO1-KO mice, indicating hampered progress in late autophagy, and was accompanied by increased p62 protein expression. Moreover, NQO1 deletion enhanced the effect of the mammalian target of the rapamycin inhibitor, rapamycin, and led to enhanced tuberous sclerosis complex 2 phosphorylation through AMP-activated protein kinase activation.
These results indicate that autophagy may be enhanced to counter the increased stress due to NQO1 deficiency, an oxidative stress barrier. The present results demonstrate the significant influence of NQO1 on the autophagy process and support the hypothesis that autophagy plays a protective role under oxidative stress conditions. Antioxid. Redox Signal. 24, 867-883.
Non-small-cell lung cancer (NSCLC) is associated with diverse genetic alterations including mutation of epidermal growth factor receptor (EGFR). Isoliquiritigenin (ILQ), a chalcone derivative, ...possesses anticancer activities. In the present study, we investigated the effects of ILQ on the growth of tyrosine kinase inhibitor (TKI)-sensitive and -resistant NSCLC cells and elucidated its underlying mechanisms. Treatment with ILQ inhibited growth and induced apoptosis in both TKI-sensitive and -resistant NSCLC cells. ILQ-induced apoptosis was associated with the cleavage of caspase-3 and poly-(ADP-ribose)-polymerase, increased expression of Bim, and reduced expression of Bcl-2. In vitro kinase assay results revealed that ILQ inhibited the catalytic activity of both wild type and double mutant (L858R/T790M) EGFR. Treatment with ILQ inhibited the anchorage-independent growth of NIH3T3 cells stably transfected with either wild type or double-mutant EGFR with or without EGF stimulation. ILQ also reduced the phosphorylation of Akt and ERK1/2 in both TKI-sensitive and -resistant NSCLC cells, and attenuated the kinase activity of Akt1 and ERK2 in vitro. ILQ directly interacted with both wild type and double-mutant EGFR in an ATP-competitive manner. A docking model study showed that ILQ formed two hydrogen bonds (Glu-762 and Met-793) with wild type EGFR and three hydrogen bonds (Lys-745, Met-793, and Asp-855) with mutant EGFR. ILQ attenuated the xenograft tumor growth of H1975 cells, which was associated with decreased expression of Ki-67 and diminished phosphorylation of Akt and ERK1/2. Taken together, ILQ suppresses NSCLC cell growth by directly targeting wild type or mutant EGFR.Non-small-cell lung cancer (NSCLC) exhibits EGFR mutation.
Treatment with isoliquiritigenin (ILQ) inhibited growth and induced apoptosis in tyrosine kinase inhibitor-sensitive and -resistant NSCLC cells. ILQ suppressed wild type and mutant (L858R/T790M) EGFR kinase activity and attenuated H1975 lung cancer cell xenograft tumor growth.
ILQ directly targets wild type or mutant EGFR.
ILQ could be a potential therapeutic agent against NSCLC.
In 2016, the Korean government selected carbon capture and utilization (CCU) as one of the national strategic projects and presented a detailed roadmap to reduce greenhouse gas emissions and to ...create new climate industries through early demonstration of CCU technology. The Korean government also established the 2030 Greenhouse Gas Reduction Roadmap in 2016 and included carbon capture, utilization, and storage (CCUS) technology in the new energy industry sector as a CCU technology. The Korean government recognizes the importance of CCUS technology as a mid- to long-term measure to reduce greenhouse gas emissions and implements policies related to technological development. The United States (U.S.), Germany, and China also expect CCUS technology to play a major role in reducing greenhouse gases in the industrial sector in terms of climate and energy policy. This study analyzed the CCU-related policies and technological trends in the U.S., Germany, and China, including major climate and energy plans, driving roadmaps, some government-led projects, and institutional support systems. This work also statistically analyzed 447 CCU and CCUS projects in Korea between 2010 and 2017. It is expected to contribute to responding to climate change, promoting domestic greenhouse gas reduction, and creating future growth engines, as well as to be used as basic data for establishing CCU-related policies in Korea.
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•The dominated bacteria in Korean rice wine mainly originated from saccharification agents.•Rice wine brewed with nuruk exhibited a distinct microbial profile with a higher proportion ...of lactic acid bacteria than koji makgeolli.•The metabolic profiles of makgeolli differed depending on the type of saccharification agent.
To brew rice wine, a saccharification agent is critical to provide sugars necessary for yeast to ferment alcohol. Nuruk, a traditional Korean saccharification agent, contains saccharification enzymes and various microorganisms, including fungi and lactic acid bacteria (LAB). To investigate the effect of saccharification agents on Korean rice wine (makgeolli), we analyzed makgeolli brewed with different saccharification agents, such as koji and nuruk. In contrast to koji makgeolli, nuruk makgeolli had a distinct microbial profile with higher proportion of LAB. Comparing the microbial profiles of the saccharification agents and makgeolli revealed that the dominant microorganisms in the makgeolli were possibly derived from the saccharification agents. Several metabolites also exhibited distinct profiles depending on the saccharification agent generating the total metabolic profile difference of makgeolli samples. Collectively, the saccharification agent could provide dominant microorganisms in the makgeolli microbiota, leading to a distinct microbial and metabolic profile of makgeolli depending on its type.
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