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The endoplasmic reticulum (ER) is responsible for structural transformation or folding of de novo proteins for transport to the Golgi. When the folding capacity of the ER is exceeded or excessive accumulation of misfolded proteins occurs, the ER enters a stressed condition (ER stress) and unfolded protein responses (UPR) are triggered in order to rescue cells from the stress. Recovery of ER proceeds toward either survival or cell apoptosis. ER stress is implicated in many pathologies, such as diabetes, cardiovascular diseases, inflammatory diseases, neurodegeneration, and lysosomal storage diseases. As a survival or adaptation mechanism, chaperone molecules are upregulated to manage ER stress. Chemical versions of chaperone have been developed in search of drug candidates for ER stress-related diseases. In this review, synthetic or semi-synthetic chemical chaperones are categorized according to potential therapeutic area and listed along with their chemical structure and activity. Although only a few chemical chaperones have been approved as pharmaceutical drugs, a dramatic increase in literatures over the recent decades indicates enormous amount of efforts paid by many researchers. The efforts warrant clearer understanding of ER stress and the related diseases and consequently will offer a promising drug discovery platform with chaperone activity.

The IC50 of BJ-1301, α-TOH, and sunitinib with respect to receptor tyrosine kinases

Specific actions of VEGF and BJ-1301 in NOX2 protein expression. Protein extracts from HUVECs treated with indicated concentration of BJ-1301 were loaded on SDS PAGE together with His-tagged human NOX1 (NOX1-1359H, Creative Biomart, NY, USA ), His+T7-tagged human NOX2 (LSG25251, LifeSpan Biosciences, WA, USA), and GST-tagged human NOX-4 (NOX4-1336H, Creative Biomart, NY, USA) recombinant proteins. Each isoform of NOX proteins was detected by using anti-NOX1 (ab55831, Abcam, MA, USA), anti-NOX2 (ab129068, Abcam, MA, USA), or anti-NOX4 (ab109225, Abcam, MA, USA) antibody. The membranes were reprobed to get the immunoblot of His, T7 or GST protein using anti-His (A00186100, Genscript, NJ, USA), anti-T7 (ab97964, Abcam, MA, USA), or anti-GST (ab19256, Abcam, MA, USA) antibody, respectively.

The IC50 values of BJ-1301, SU4312, and α-TOH on ROS production induced by VEGF and TPA

Primer sequences used in the PCR experiments

The Absolute mRNA expression (Ct andã…¿Ct values*) of NOX isoforms and regulatory subunits in A549 and H1299 cells

Comparison of ID50 of BJ-1301 and α-TOH in VEGF-induced angiogenesis in vivo

Chlorophyll-rich samples, such as kale, interfere with the analysis of residual pesticides and adversely affect the integrity of tandem mass spectrometers. Dispersed solid-phase (d-SPE) extraction using graphitized carbon black effectively removes pigments from kale extracts; however, it also reduces the recoveries of 30 pesticides. To overcome this, alternative sorbents, including ENVI-Carb, ChloroFiltr, and Z-Sep+, were evaluated in this study. A sorbent combination based on 50 mg of Z-Sep+ was most advantageous (21/30), good precision (

Introduction Endoplasmic reticulum (ER) stress condition is characterized as the accumulation of misfolded or unfolded proteins in lumen of ER. This condition has been implicated in various diseases and pathologies including β-cell apoptosis, Alzheimer’s disease and atherosclerosis. We have reported that hydroxynaphthoic acids (HNA), naphthalene analogues of salicylic acid (SA), reduced ER stress. In this study, we explored structural modification to bi-aryl analogues of SA. Methods Palladium-catalyzed cross-coupling was applied to synthesize bi-aryl analogues of SA. Anti-ER stress activity was monitored by using our cell-based assay system where ER stress is induced by tunicamycin. To monitor ER stress markers, ER stress was induced physiologically relevant palmitate system. Results Many analogues decreased ER stress signal induced by tunicamycin. Compounds creating dihedral angle between Ar group and SA moiety generally increased the activity but gave some cytotoxicity to indicate the crucial role of flat conformation of aromatic region. The best compound (16e) showed up to almost 6-fold and 90-fold better activity than 3-HNA and tauro-ursodeoxycholic acid, positive controls, respectively. ER stress markers such as p-PERK and p-JNK were accordingly decreased in Western blotting upon treatment of 16e under palmitate-induced condition. Conclusion Anti-ER stress activity and toxicity profile of bi-aryl analogues of SA could provide a novel platform for potential therapy for protein misfolding diseases., Graphical Abstract

To identify potent antiviral compounds, we introduced a high-throughput screen platform that can rapidly classify hit compounds according to their target. In our platform, we performed a compound screen using a lentivirus-based pseudovirus presenting a spike protein of coronavirus, and we evaluated the hit compounds using an amplified luminescence proximity homogeneous assay (alpha) test with purified host receptor protein and the receptor binding domain of the viral spike. With our screen platform, we were able to identify both spike-specific compounds (class I) and broad-spectrum antiviral compounds (class II). Among the hit compounds, thiosemicarbazide was identified to be selective to the interaction between the viral spike and its host cell receptor, and we further optimized the binding potency of thiosemicarbazide through modification of the pyridine group. Among the class II compounds, we found raloxifene and amiodarone to be highly potent against human coronaviruses including Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus (SARS-CoV), and SARS-CoV-2. In particular, using analogs of the benzothiophene moiety, which is also present in raloxifene, we have identified benzothiophene as a novel structural scaffold for broad-spectrum antivirals. This work highlights the strong utility of our screen platform using a pseudovirus assay and an alpha test for rapid identification of potential antiviral compounds and their mechanism of action, which can lead to the accelerated development of therapeutics against newly emerging viral infections.

Common buckwheat sprout (CBS) contains more flavone C-glycosides (FCGs) and flavonol O-glycosides (FOGs) than does common buckwheat seed. Both flavonoids in CBS are well known for providing benefits to human health. However, they are relatively less bioaccessible and more directly degradable to aglycone during digestion than are multiglycosylated flavonoids. To overcome such limitations, the water solubility and digestion stability of FCGs and FOGs were enhanced by transglycosylation using cyclodextrin glycosyltransferase. Gastric conditions had little effect on the stability of FCGs and FOGs and their enzyme-modified compounds. In contrast, under intestinal conditions, transglycosylated FCGs lost a glucose moiety and reverted to their parent compounds before transglycosylation. Under colonic fermentation using human fecal samples, the different profiles and concentrations of short-chain fatty acids were suggested to be mainly due to the presence of transglycosylated FCGs and FOGs. These findings indicate that the process of transglycosylation changes the bioaccessibility of flavonoids in CBS.

The amino acid concentration of soybean products is important for nutritional and health benefits along with desirable sensory characteristics, but these properties could be affected by the origin of raw ingredients, processing method, and storage. Here, we aimed to evaluate the compositional characteristics of free amino acids in soybean paste and identify potential differences between those generated by traditional and nontraditional manufacturing processes. We developed and validated a high-performance liquid chromatography-diode array detection (HPLC-DAD) method involving sample derivatization to analyze 21 free amino acids in soybean pastes. All amino acid compounds were separated within 45 min using a C18 column (250 mm × 4.6 mm, 3 μm). Validation of the optimized 21 free amino acid analysis method showed good linearity (R2 > 0.993), accuracy (≥ 80%), intra- (≤10.63%) and inter-day (≤ 11.58%) repeatability, and limit of quantification (0.025–1.91 µg/g). The levels of 21 free amino acids in nontraditional and traditional soybean pastes detected based upon the optimized method were total amino acid detection levels at 55.3–150.9 (average 92.7) and 49.6–143.4 (average 86.8) mg/kg, respectively. Moreover, we confirmed that the composition ratios of glutamic acid, histidine, and sacrosine were higher in nontraditional soybean paste manufacturing methods (p

Platinum (Pt)-based anticancer drugs such as cisplatin have been used to treat various cancers. However, they have some limitations including poor selectivity and toxicity towards normal cells and increasing chemoresistance. Therefore, there is a need for novel metallo-anticancers, which has not been met for decades. Since the initial introduction of ruthenium (Ru) polypyridyl complex, a number of attempts at structural evolution have been conducted to improve efficacy. Among them, half-sandwich Ru-arene complexes have been the most prominent as an anticancer platform. Such complexes have clearly shown superior anticancer profiles such as increased selectivity toward cancer cells and ameliorating toxicity against normal cells compared to existing Pt-based anticancers. Currently, several Ru complexes are under human clinical trials. For improvement in selectivity and toxicity associated with chemotherapy, Ru complexes as photodynamic therapy (PDT), and photoactivated chemotherapy (PACT), which can selectively activate prodrug moieties in a specific region, have also been investigated. With all these studies on these interesting entities, new metallo-anticancer drugs to at least partially replace existing Pt-based anticancers are anticipated. This review covers a brief description of Ru-based anticancer complexes and perspectives.

A simple, rapid and reliable extraction method for allulose content in jelly were optimized using response surface methodology. The extraction method was selected based on preliminary experiments, with a three-factor, three-level central complex design including 20 experimental runs to optimize the extraction parameters. The optimum extraction factors predicted were temperature of 66 °C, solvent of 74% (v/v) ethanol, and extraction time of 24 min under shaking water bath extraction. The measured parameters were in accordance with the predicted values. The developed analytical method was validated with regard to linearity, accuracy and precision presenting recovery level from 90.79 to 95.18% and detection limits varying from 0.53 to 1.62 mg/mL. Finally, the method will be potentially applicable to a commercial jelly food using optimum extraction. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13197-020-04773-z) contains supplementary material, which is available to authorized users.

We sought to investigate the effect of extracts from Rosa gallica petals (RPE) on skin whitening and anti-wrinkle activity. Tyrosinase activity was attenuated by RPE treatment, concomitant with the reduction of melanin accumulation in human B16F10 melanoma. Treatment of the facial skin of volunteers in a clinical trial with an RPE-containing formulation enhanced skin brightness (L* value) significantly. The underlying mechanism responsible was determined to be associated with mitogen-activated protein kinase (MAPK) activation. In addition, RPE exhibited anti-wrinkle formation activity of human dermal fibroblasts by suppressing matrix metalloproteinase (MMP)-1 level. In vivo study, RPE also inhibited solar ultraviolet-stimulated MMP-1 level by c-Jun regulation. Overall, our findings indicate that RPE evokes skin whitening and anti-wrinkle formation activity by regulating intracellular signaling, supporting its utility as an ingredient for skin whitening and anti-wrinkle cosmetic products.

Newly developed magnetic carbon particles prepared from coffee grounds were used as the sorbent for the magnetic solid-phase extraction of eight phthalic acid esters (PAEs) from plastic bottled water prior to their analysis by GC-MS. The method, which uses coffee-ground particles coated with iron oxide, was validated, and exhibited linearities for the eight PAEs, with coefficients of determination above 0.998 in the 0.005 to 0.1 mg/L concentration range. Limits of detection and limits of quantification of 0.00003 to 0.002 mg/L and 0.0001 to 0.005 mg/L, respectively, were achieved, with recoveries (%) ranging between 77% and 120%, and relative standard deviations for intra- and interday precisions below 16.3% at three fortification levels. No PAE residues were detected when the developed and validated method was applied to 10 real plastic bottled water samples. Taken together, the developed magnetic solid-phase extraction method is a useful tool for monitoring phthalate esters in aqueous samples. PRACTICAL APPLICATION: The development of a new, inexpensive, and efficient magnetic sorption material derived from spent coffee grounds, and its ability to determine phthalate esters in aqueous solutions was described by GC-MS/MS. The developed magnetic solid-phase extraction method is a useful tool for monitoring phthalate esters in aqueous samples.

Soybeans, Glycine max (L.) Merr., are among the most important food crops worldwide. Isoflavones are major bioactive phytochemicals in soybeans, and have a variety of health benefits, including antioxidative, antiatherosclerotic, antiinflammatory, and weak estrogen-like effects. The isoflavone content and composition of soybeans vary according to the cultivar and the extraction solvent conditions. Therefore, we investigated the effects of three different solvent pHs (1.0, 5.5, and 10.0) on the isoflavone, total phenolic, and total flavonoid contents and antioxidant capacities of eight soybean cultivars developed in Korea. Twelve isoflavones in soybeans were efficiently separated and identified on a reversed-phase high-performance liquid chromatography (HPLC) system. The percentage distribution of isoflavones measured by HPLC in the eight soybean cultivars at various extraction pHs decreased as follows: malonyl isoflavones (67.2% to 81.3%) > isoflavone glucosides (16.2% to 29.0%; as nonacylated form) > acetyl isoflavones (1.6% to 5.9%). The highest contents of isoflavone glucosides, malonyl derivatives, and acetyl derivatives were extracted at solvent pHs of 10.0, 1.0, and 5.5, respectively. The solvent extraction at pH 1.0 yielded a lower total isoflavone content than those at pHs 5.5 and 10.0. However, the highest total phenolic and flavonoid contents were extracted from soybeans at pH 1.0. Soybeans extracted at pH 10.0 displayed the highest antioxidant capacities in the 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical assay. Taken together, these results suggest that proper solvent pH adjustment is needed to maximize the extraction of targeted forms of isoflavones from soybeans. PRACTICAL APPLICATION: Soybeans contain a variety of bioactive compounds, including isoflavones, which function as antioxidants and weak phytoestrogens. Chemical and instrumental analyses can facilitate the selection of soybean cultivars with high amounts of isoflavones for soybean breeding and isoflavone-enriched product development. Proper solvent pH adjustment allows for the efficient extraction of high amounts of targeted isoflavone subgroups (acetyl and malonyl forms) from soybeans for functional food products.

Modification of chestnut starch with amylosucrase from Deinococcus geothermalis (DGAS) increases the proportion of resistant starch. DGAS-modified chestnut starch (DMCS) attenuates obesity in diet-induced obese mice via a receptor of short chain fatty acids (SCFAs), G-protein-coupled receptor 43. SCFAs are gut microbial metabolites produced by fermenting resistant starch and have key roles in the obesity-ameliorating effects of DMCS. Here, we evaluated the mechanical links among DMCS-induced changes in the gut microbiota, consequent production of microbial metabolites, and host genetic responses. Supplementation with DMCS altered the proportions of cecal microbiota, such as Ruminococcaceae and Bacteroides; microbial metabolites, such as acetic acid; and some carbohydrate metabolites. DMCS also induced changes in the expression of some genes in cecal epithelial cells, including genes involved in energy production, the cell cycle, and cellular junctions. Changes in the gut microbiota, microbial metabolites, and host gene expression were found to be significantly correlated. Our findings demonstrated the integrated and incorporated association among the gut microbiota, their beneficial metabolites, and the host transcriptome, which contributed to clarifying the anti-obesity effects of DMCS as a prebiotic. Therefore, fortifying resistant starch by modification of chestnut starch using DGAS may be a good strategy in the functional food industry.

Phenolic compounds in common buckwheat sprouts (CBSs) have gained research interest because of their multiple health benefits. Phenolic acids, flavanones, flavonols, flavan-3-ols, and anthocyanins are important bioactive components of CBS that exhibit biological activities, including anti-inflammatory, antioxidant, anti-proliferative, and immunomodulatory effects. The isolation and quantitative and qualitative analyses of these phenolic compounds require effective and appropriate extraction and analytical methods. The most recent analytical method developed for determining the phenolic profile is HPLC coupled with a UV-visible detector and/or MS. This review highlights the extraction, purification, analysis, and bioactive properties of phenolic compounds from CBS described in the literature.

This study was designed to determine the residual trichothecene mycotoxins in cereal samples. The optimal solvent for extraction was 84% (v/v) aqueous acetonitrile with 1% (v/v) formic acid. The best performing clean-up method was dispersive-solid phase with a mixture octadecyl silica and primary-secondary amine. The recoveries for the studied mycotoxins ranged from 83.3 to 92.8%. The methodology was successfully applied for monitoring 100 cereal samples obtained from a Korean market. The bean sample were found to be co-contamination with deoxynivalenol and HT-2 toxin. Deoxynivalenol possessed the highest detection freauency (4/100) and amount (727.38 µg/kg) among the trichothecene mycotoxins. The hazard index was less than 1.0 for all the observed mycotoxins in all cereal samples except one white rice sample (1.2681). This results indicated that periodic risk assessments of trichothecene mycotoxin through cereal intake are necessary for the health and safety.

Rosa gallica is a widely used Rosa species for medicinal and culinary purposes. Rosa gallica has been reported to display antioxidant, anti−inflammatory, and antibacterial activities. However, the effect of Rosa gallica against skin aging in vivo is unknown and its active components have not been fully understood. Oral administration of Rosa gallica prevented UVB−mediated skin wrinkle formation and loss of collagen/keratin fibers in the dorsal skin of mice. Examination of biomarkers at the molecular level showed that Rosa gallica downregulates UVB−induced COX−2 and MMP−1 expression in the skin. Through a direct comparison of major compounds identified using the UHPLC−MS/MS system, we discovered gallic acid as the primary component contributing to the anti-skin aging effect exhibited by Rosa gallica. Examination of the molecular mechanism revealed that gallic acid can potently and selectively target the c−Raf/MEK/ERK/c−Fos signaling axis. In addition, both gallic acid and MEK inhibitor blocked UVB−induced MMP−1 expression and restored collagen levels in a reconstructed 3D human skin model. Collectively, Rosa gallica could be used as a functional ingredient in the development of nutraceuticals against skin aging.

During refrigerated storage, aged beef is liable to undergo alterations in its physicochemical properties. This study aimed to evaluate changes in the community of microorganisms, volatile compounds, and amino acids in aged beef under cold storage conditions. In addition, volatile basic nitrogen (VBN) values were measured to determine the putrefaction degree. Raw-, dry-, and wet-aged beef were stored at 4°C for 21 days. The initial pH of beef under the three conditions ranged from 5.52 to 5.60 and decreased from 5.04 to 5.33 over time. After 21 days, VBN values ranged 20.53-22.59 mg/100 g, which exceeded the standard of spoilage (20 mg/100 g) in the Korean Food Code. As time passed, numbers of psychrophilic and lactic acid bacteria increased in the raw beef. In contrast, number of mesophilic, psychrophilic, and lactic acid bacteria decreased in dry- and wet-aged beef. Among the volatile substances and amino acids, 2,3-butanedione, 2-butanone, tyrosine, and arginine contributed the most to the high VBN levels in aged beef, where the VBN was 21 mg/100 g at 21 days, which was beyond the acceptable limit. In conclusion, clear alterations were observed in the physicochemical properties and microorganism communities in cold-stored aged beef, providing basic information that could benefit the beef industry and boost consumer acceptance.

The practice of abusing antibiotics to improve livestock growth poses a threat to food safety. To prevent and regulate this, accurate monitoring of residual veterinary drugs (VDs) is required. A method based on QuEChERS with dispersive solid-phase extraction for the determination of multi-class VDs was investigated using selected product ions under optimized multiple reaction monitoring conditions. During the clean-up procedure, chitosan, octadecyl silica, primary-secondary amine, and enhanced matrix removal (EMR)-lipid were evaluated for simultaneous analysis of multi-class VDs in beef matrix. The EMR sorbent was most advantageous (113/115) compared to others, and showed a satisfactory recovery range (70.7-117.9%) except cefquinome (67.3%) and cefalonium (69.8%). This methodology can be used to detect oxolinic acid and ractopamine (27.4% and 88.0% of maximum residue limit, respectively) in real beef samples. We thus study propose a simple and fast analytical method for multi-class VDs for the future health of humans and animals.

Rosa gallica is a widely used Rosa species for medicinal and culinary purposes. Rosa gallica has been reported to display antioxidant, anti−inflammatory, and antibacterial activities. However, the effect of Rosa gallica against skin aging in vivo is unknown and its active components have not been fully understood. Oral administration of Rosa gallica prevented UVB−mediated skin wrinkle formation and loss of collagen/keratin fibers in the dorsal skin of mice. Examination of biomarkers at the molecular level showed that Rosa gallica downregulates UVB−induced COX−2 and MMP−1 expression in the skin. Through a direct comparison of major compounds identified using the UHPLC−MS/MS system, we discovered gallic acid as the primary component contributing to the anti-skin aging effect exhibited by Rosa gallica. Examination of the molecular mechanism revealed that gallic acid can potently and selectively target the c−Raf/MEK/ERK/c−Fos signaling axis. In addition, both gallic acid and MEK inhibitor blocked UVB−induced MMP−1 expression and restored collagen levels in a reconstructed 3D human skin model. Collectively, Rosa gallica could be used as a functional ingredient in the development of nutraceuticals against skin aging.

Misfolded or unfolded proteins are accumulated in lumen of endoplasmic reticulum (ER) in ER stress condition. It has been implicated in many pathological conditions such as Alzheimer’s disease, diabetic retinopathy, atherosclerosis, β-cell apoptosis and lung inflammation. We found a series of N-substituted-2-arylcarbonylhydrazinecarbothioamides to potently decrease ER stress signal, showing up to almost 300-fold better activity than 1-hydroxynaphthoic acid and tauro-ursodesoxycholic acid, positive controls, respectively. Structure−activity relationship (SAR) study showed that 2-arylcarbonyl moiety is critical for the activity of the hydrazinecarbothioamide analogues and side chains tethering on thioamide moiety were relatively insensitive to the activity. Some analogues were found to consistently exert the potency under more physiologically relevant condition where ER stress was induced by palmitic acid. ER stress markers such as CHOP and phosphorylated eIF2α and PERK were accordingly decreased in western blotting upon treatment of compound 4h. Potential ER stress inhibitory activity and novel structures could provide a novel platform for new chemical chaperone and therapy for protein misfolding diseases.

Pesticides are used to increase crop yields and preserve quality by protecting crops against pests; however, their overuse can adversely affect human health and the environment. Herein, we report the development of a multi-pesticide screening method using optimized QuEChERS coupled with liquid chromatography/quadrupole time-of-flight (QTOF) mass spectrometry for the analysis of 13 pesticides in wheat flour. Mass accuracies with errors of less than 2.4 ppm were obtained for all analysed pesticides, and the method provided satisfactory recovery and linearity. Repeatabilities of 0.3-12.7% and reproducibilities of 2.5-15.2% were observed in full-scan TOF mode. The performance of the developed full-scan TOF method was compared to that obtained in high-resolution multiple reaction monitoring (MRM-HR) mode. The limits of quantification for the full-scan TOF and MRM-HR modes ranged from 2 to 10, and 3 to 9 μg kg

The anti-skin inflammatory activities of rose petal extracts have been described in our previous study. Because skin inflammation is closely linked to skin aging, our study investigated the effects of Rosa gallica petals on skin aging-related activities such as skin whitening and anti-wrinkle properties. Each sample was prepared via extraction using different ethanol ratios with the objective of evaluationg optimal extraction conditions for industrial application. Aqueous 50% (v/v) EtOH extract of R. gallica petal significantly suppressed tyrosinase activity, melanin production, and solar UV-induced matrix metalloproteinase-1, a hall mark of wrinkle formation. In addition, the aqueous 50% (v/v) EtOH extract showed the highest antioxidative effect and had highest flavonoid contents, consistent with the reported anti-aging effects. Overall, our findings suggest that R. gallica petals extracts exhibit anti-aging effects. Furthermore, 50% EtOH extraction, in particular, was optimal for the highest anti-aging, and anti-oxidative effects as well as to obtain the highest flavonoid content.

Herein, a QuEChERS (quick, easy, cheap, effective, rugged, and safe) procedure together with liquid chromatography and tandem mass spectrometry was applied to the multi-residue analysis of 203 pesticides in strawberries. To reduce the amount of co-eluents, we compared several dispersive solid-phase extraction cleanup procedures and found that cleanup using octadecylsilane provided the best recoveries. Spiked-sample recoveries of 70–120% with relative standard deviations of 0.99), and the limits of quantification (LOQs) were lower than the maximum residue limits recommended by the European Commission and Korea Food and Drug Administration. The developed method was applied to real samples, revealing that their pesticide contents exceeded the corresponding LOQs. The obtained results demonstrate that octadecylsilane-based dispersive solid-phase extraction is a rapid and high-throughput cleanup procedure for the multi-residue analysis of pesticides in strawberries.

3,3′,4′,5,7-Pentahydroxyflavone-3-rhamnoglucoside (rutin) is a flavonoid with a wide range of pharmacological activities. Dietary rutin is hardly absorbed because the microflora in the large intestine metabolize rutin into a variety of compounds including quercetin and phenol derivatives such as 3,4-dihydroxyphenolacetic acid (DHPAA), 3,4-dihydroxytoluene (DHT), 3,4-hydroxyphenylacetic acid (HPAA) and homovanillic acid (HVA). We examined the potential of rutin and its metabolites as novel histone acetyltransferase (HAT) inhibitors. DHPAA, HPAA and DHT at the concentration of 25 μM significantly inhibited in vitro HAT activity with DHT having the strongest inhibitory activity. Furthermore, DHT was shown to be a highly efficient inhibitor of p300 HAT activity, which corresponded with its high degree of inhibition on intracellular lipid accumulation in HepG2 cells. Docking simulation revealed that DHT was bound to the p300 catalytic pocket, bromodomain. Drug affinity responsive target stability (DARTS) analysis further supported the possibility of direct binding between DHT and p300. In HepG2 cells, DHT concentration-dependently abrogated p300-histone binding and induced hypoacetylation of histone subunits H3K9, H3K36, H4K8 and H4K16, eventually leading to the downregulation of lipogenesis-related genes and attenuating lipid accumulation. In ob/ob mice, administration of DHT (10, 20 mg/kg, iv, every other day for 6 weeks) dose-dependently improved the NAFLD pathogenic features including body weight, liver mass, fat mass, lipid accumulation in the liver, and biochemical blood parameters, accompanied by the decreased mRNA expression of lipogenic genes in the liver. Our results demonstrate that DHT, a novel p300 histone acetyltransferase inhibitor, may be a potential preventive or therapeutic agent for NAFLD.

Agricultural water is closely linked to surface and ground water as well as soil, hence, ensuring its safety is an important endeavor. We used the &ldquo, quick, easy, cheap, effective, rugged, and safe&rdquo, (QuEChERS) method to analyze multi-residue pesticides in agricultural water by using a combined-sorbent-based clean-up procedure. Among the various sorbents examined, clean-up using ENVI-Carb combined with a primary secondary amine sorbent delivered the highest recovery of multi-residue pesticides (&gt, 93.9%). While the developed method showed satisfactory linearity (R2 &gt, 0.9991), precision, and specificity, recovery was low for pyrazolate (29.1%) and thidiazuron (59.2%). The limits of detection and quantification for the 55 pesticides targeted in this study were in 0.02&ndash, 3.0 &mu, g L&minus, 1 and 0.1&ndash, 9.9 &mu, 1, respectively. The developed method was used to identify and quantify multi-residue pesticides during sample analysis. The results suggest that the QuEChERS method employing a combination of ENVI-Carb and another sorbent can be applied for the effective analysis of multi-residue pesticides in agricultural water.

We sought to investigate the effect of extracts from

6-Aminopyridin-3-ol scaffold has shown an excellent anti-inflammatory bowel disease activity. Various analogues with the scaffold were synthesized in pursuit of the diversity of side chains tethering on the C(6)-position. Structure-activity relationship among the analogues was investigated to understand the effects of the side chains and their linkers on their anti-inflammatory activities. In this study, structural modification moved beyond side chains on the C(6)-position and reached to pyridine ring itself. It expedited us to synthesize diverse ring-modified analogues of a representative pyridine-3-ol, 6-acetamido-2,4,5-trimethylpyridin-3-ol (9). In the evaluation of compounds on their inhibitory actions against TNF-α-induced adhesion of monocytic cells to colonic epithelial cells, an in vitro model mimicking colon inflammation, the effects of compounds 9, 17, and 19 were greater than tofacitinib, an orally available anti-colitis drug, and compound 17 showed the greatest activity. In addition, TNF-α-induced angiogenesis, which permits more inflammatory cell migration into inflamed tissues, was significantly blocked by compounds 17 and 19 in a concentration-dependent manner. In the comparison of in vivo therapeutic effects of compounds 9, 17, and 19 on dextran sulfate sodium (DSS)-induced colitis in mice, compound 17 was the most potent and efficacious, and compound 19 was better than compound 9 which showed a similar degree of inhibitory effect to tofacitinib. Taken together, it seems that either the trimethyl system or the hydroxyl group on the pyridinol ring is essential to the activity. This finding might become a new milestone in the development of pyridinol-based anti-inflammatory bowel disease agents.

Isoflavones in soybeans are well-known phytoestrogens. Soy isoflavones present in conjugated forms are converted to aglycone forms during processing and storage. Isoflavone aglycones (IFAs) of soybeans in human diets have poor solubility in water, resulting in low bioavailability and bioactivity. Enzyme-mediated glycosylation is an efficient and environmentally friendly way to modify the physicochemical properties of soy IFAs. In this study, we determined the optimal reaction conditions for Deinococcus geothermalis amylosucrase-mediated α-1,4 glycosylation of IFA-rich soybean extract to improve the bioaccessibility of IFAs. The conversion yields of soy IFAs were in decreasing order as follows: genistein &gt, daidzein &gt, glycitein. An enzyme quantity of 5 U and donor:acceptor ratios of 1000:1 (glycitein) and 400:1 (daidzein and genistein) resulted in high conversion yield (average 95.7%). These optimal reaction conditions for transglycosylation can be used to obtain transglycosylated IFA-rich functional ingredients from soybeans.

Branch-chain elongated starches can be synthesized by amylosucrase (AS). In this study, potato starches with different branch-chain length were produced using the temperature-dependent elongation property of AS from Deinococcus geothermalis (DGAS). Decreasing the reaction temperature led to a significant rise in the length of the branch-chains, in addition to amylose content. As branch-chain length increased, B-type crystal structure increased significantly alongside it, and the thermal transitions were enhanced, suggesting that the crystalline structure was further stabilized. In addition, a decrease in solubility and swelling power was observed, whereas the gelatinization temperatures and peak viscosities increased accordingly. With respect to digestive properties, a remarkable rise in slowly digestible starch (0–19.8%) and resistant starch (38.2%–62.2%) contents was observed, along with an enhanced resistance to mammalian mucosal α-glucosidase. In conclusion, enzymatic modification by DGAS might be an innovative method to regulate the physicochemical and digestive properties of starches.

Nonalcoholic fatty liver disease (NAFLD) is an increasingly studied condition that can progress to end-stage liver disease. Although NAFLD was first described in 1980, a complete understanding of the mechanism and causes of this disease is still lacking. Six-transmembrane protein of prostate 2 (STAMP2) plays a role in integrating inflammatory and nutritional signals with metabolism. Our previous study suggested that STAMP2 may be a suitable target for treating NAFLD. In the current study, we performed a focused drug-screening and found that cilostazol could be a potential STAMP2 enhancer. Thus, we examined whether cilostazol alleviates NAFLD through STAMP2. The in vivo and in vitro pharmacological efficacies of cilostazol on STAMP2 expression and lipid accumulation were analyzed in NAFLD mice induced by high-fat diet (HFD) and in HepG2 cell lines treated by oleic acid (OA), respectively. Cilostazol increased the expression of STAMP2 through transcriptional regulation in vivo and in vitro. Cilostazol also dampened the STAMP2 downregulation caused by the HFD and by OA in vivo and in vitro, respectively. Cilostazol activated AMP-activated protein kinase (AMPK) in vivo and in vitro, and AMPK functions upstream of STAMP2, and reversed downregulation of STAMP2 expression through AMPK in the NAFLD model. Cilostazol ameliorates hepatic steatosis by enhancing hepatic STAMP2 expression through AMPK. Enhancing STAMP2 expression with cilostazol represents a potential therapeutic avenue for treatment of NAFLD.

The aim of this study was to investigate the skin anti‐inflammatory activity of rose petal extract (RPE) and the mechanisms underlying this phenomenon. Recently, flowers have been considered as dietary resources owing to their biological activities, such as inhibition of nephritis and hemorrhoids. The Rosa plant exerts various biological functions, including antioxidant and anti‐microbiological activities. Herein, we confirmed the skin anti‐inflammatory activity of RPE upon solar UV (sUV) exposure. RPE reduced sUV‐induced COX‐2 expression as well as expressions of several cytokines. Activation of MKK4‐JNK, MEK‐ERK, and MKK3‐p38 signaling pathways, which are associated with cytokine production, was also attenuated by RPE treatment. We hypothesized these RPE‐induced changes are because of its antioxidant activity, because RPE displayed drastic radical scavenging and oxygen radical absorbance capacity (ORAC). Furthermore, high anthocyanins, polyphenols, and flavonoids contents were found in RPE. Hence, these results indicated the skin anti‐inflammatory activity of RPE is because of antioxidant activity.

Enhanced expression of NADPH oxidase (NOX) and the subsequent production of reactive oxygen species (ROS) are associated with lung cancer. In the present study, fifty 6-amino-2,4,5-trimethylpyridin-3-ol derivatives were screened for anticancer activity by targeting NOX2-derived ROS. The compounds suppressed ROS production and decreased cancer cell viability (R2 = 0.79). Among the derivatives, the compound coded BJ-1207, which contained a 4-(hydroxydiphenylmethyl)piperidine moiety, exhibited the most effective anticancer activity against A549 lung cancer cell line and eight other cancer cell lines, including H1299, MCF-7, MDA-MB-231, HT-29, SW620, Mia PaCa-2, PANC-1, and U937. BJ-1207 also showed significantly lower inhibitory effects on kinase insert domain receptor (KDR) and c-KIT tyrosine kinase but higher inhibitory activity on NOX than those of sunitinib, a multi-receptor tyrosine kinase (RTK) inhibitor. In addition, BJ-1207-induced inhibition of RTK-downstream signaling pathways, such as ROS production, and expression of target genes, such as stem cell factor and transforming growth factor-α, were similar to those induced by sunitinib. In the xenograft chick tumor model, BJ-1207 inhibited lung tumor growth to a similar or much greater extent than that of sunitinib or cisplatin, respectively. Overall, the present study showed that BJ-1207, a vitamin B6-derived 2,4,5-trimethylpyridin-3-ol compound with azacyclonol moiety at C (6)-position of the pyridine ring, inhibited NOX activity and that it is a promising lead compound for developing anticancer drugs against lung cancer.

A rapid analytical method was developed for the determination of 4-methylimidazole from red ginseng products containing caramel colors by using dispersive liquid-liquid microextraction with in situ derivatization followed by gas chromatography with mass spectrometry. Chloroform and acetonitrile were selected as the extraction and dispersive solvents, and based on the extraction efficiency, their optimum volumes were 200 and 100 μL, respectively. The optimum volumes of the derivatizing agent (isobutyl chloroformate) and catalyst (pyridine), pH, and concentration of NaCl in the sample solution were determined to be 25 and 100 μL, pH 7.6, and 0% w/v, respectively. Validation of the optimized method showed good linearity (R2 > 0.999), accuracy (≥89.86%), intra- (≤6.70%) and interday (≤4.17%) repeatability, limit of detection (0.96 μg/L), and limit of quantification (5.79 μg/L). The validated method was applied to quantify 4-methylimidazole in red ginseng juices and concentrates, 4-methylimidazole was only found in red ginseng juices containing caramel colorant (42.91-2863.4 μg/L) and detected in red ginseng concentrates containing >1% caramel colorant.

Ginseng (Panax ginseng Meyer) is widely used to treat various chronic disorders. Black ginseng is obtained by repeated steaming and drying of raw ginseng, which turn it black and convert the ginsenoside compounds present into more potent bioactive ingredients. The effects of a black ginseng extract on melanin production and skin whitening were evaluated in vitro as well as in vivo using human skin and zebrafish embryos. Tyrosinase activity decreased when steamed and dried ginseng was used. A pronounced skin-whitening effect was observed in our clinical study, and inhibition of melanin activity and tyrosinase levels was confirmed in zebrafish embryos. Two ginsenosides specific to black ginseng activate the MEK-ERK signaling pathway and are the main factors responsible for skin whitening. The skin-whitening effects of black ginseng are associated with the formation of two ginsenosides, indicating that black ginseng can be used as a novel skin-whitening agent in cosmetic products.