Korea Research Institute of Bioscience and Biotechnology
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Synthesis of spirooxindoles bearing 1,3-oxathiolane-2-thione moiety from isatin-derived propargylic alcohols
No full textSpirooxindoles bearing 1,3-oxathiolane-2-thione moiety were synthesized from isatin-derived propargylic alcohols and carbon disulfide in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). The spirooxindoles were formed stereoselectively via attack of the alkoxide of propargylic alcohol to carbon disulfide to form xanthate anion and a following 5-exo-dig cyclization process.
Effects of Hahella chejuensis-derived prodigiosin on UV-induced ROS production, inflammation and cytotoxicity in HaCaT human skin keratinocytes
No full textProdigiosins, which are natural tripyrrole red pigments and synthetic derivatives, reportedly have multiple biological effects mainly on various types of cancer cells. However, the effects of bacterial prodigiosin on non-cancerous HaCaT human skin keratinocytes have not been reported. Therefore, the present study aimed to investigate the functional activities of prodigiosin derived from cultures of the bacterium Hahella chejuensis in HaCaT cells. Cell viability, the cell proliferation rate, and reactive oxygen species (ROS) production in vitro were assayed following treatment of HaCaT cells with prodigiosin. Prodigiosin did not cause cytotoxicity and notably increased proliferation of HaCaT cells. Furthermore, prodigiosin reduced ultraviolet (UV) irradiation-induced ROS production and the inflammatory response in HaCaT cells. More importantly, prodigiosin reduced matrix metalloproteinase-9 expression and increased collagen synthesis in UV-irradiated HaCaT cells, demonstrating that it elicits anti-aging effects. In conclusion, our results reveal that H. chejuensis-derived prodigiosin is a potential natural product to develop functional cosmetic ingredients.
Metabolite profiling and characterization of LW6, a novel HIF-1α inhibitor, as an antitumor drug candidate in mice
No full textA novel HIF (hypoxia-inducible factor)-1α inhibitor, the (aryloxyacetylamino)benzoic acid derivative LW6, is an anticancer agent that inhibits the accumulation of HIF-1α. The aim of this study was to characterize and determine the structures of the metabolites of LW6 in ICR mice. Metabolite identification was performed using a predictive multiple reaction monitoring-information dependent acquisition-enhanced product ion (pMRM-IDA-EPI) method in negative ion mode on a hybrid triple quadrupole-linear ion trap mass spectrometer (QTRAP). A total of 12 metabolites were characterized based on their MS/MS spectra, and the retention times were compared with those of the parent compound. The metabolites were divided into five structural classes based on biotransformation reactions: amide hydrolysis, ester hydrolysis, mono-oxidation, glucuronidation, and a combination of these reactions. From this study, 2-(4-((3r,5r,7r)-adamantan-1-yl)phenoxy)acetic acid (APA, M7), the metabolite produced via amide hydrolysis, was found to be a major circulating metabolite of LW6 in mice. The results of this study can be used to improve the pharmacokinetic profile by lowering the clearance and increasing the exposure relative to LW6.
Assessment of Erythrobacter species diversity through pan-genome analysis with newly isolated Erythrobacter sp. 3-20A1M
No full textErythrobacter species are extensively studied marine bacteria that produce various carotenoids. Due to their photoheterotrophic ability, it has been suggested that they play a crucial role in marine ecosystems. It is essential to identify the genome sequence and the genes of the species to predict their role in the marine ecosystem. In this study, we report the complete genome sequence of the marine bacterium Erythrobacter sp. 3-20A1M. The genome size was 3.1 Mbp and its GC content was 64.8%. In total, 2998 genetic features were annotated, of which 2882 were annotated as functional coding genes. Using the genetic information of Erythrobacter sp. 3-20A1M, we performed pangenome analysis with other Erythrobacter species. This revealed highly conserved secondary metabolite biosynthesis-related COG functions across Erythrobacter species. Through subsequent secondary metabolite biosynthetic gene cluster prediction and KEGG analysis, the carotenoid biosynthetic pathway was proven conserved in all Erythrobacter species, except for the spheroidene and spirilloxanthin pathways, which are only found in photosynthetic Erythrobacter species. The presence of virulence genes, especially the plant-algae cell wall degrading genes, revealed that Erythrobacter sp. 3-20A1M is a potential marine plant-algae scavenger.
Synergistic effect of methyl jasmonate and abscisic acid co-treatment on avenanthramide production in germinating oats
No full textThe oat (Avena sativa L.) is a grain of the Poaceae grass family and contains many powerful anti-oxidants, including avenanthramides as phenolic alkaloids with anti-inflammatory, anti-oxidant, anti-itch, anti-irritant, and anti-atherogenic activities. Here, the treatment of germinating oats with methyl jasmonate (MeJA) or abscisic acid (ABA) resulted in 2.5-fold (582.9 mg/kg FW) and 2.8-fold (642.9 mg/kg FW) increase in avenanthramide content, respectively, relative to untreated controls (232.6 mg/kg FW). Moreover, MeJA and ABA co-treatment synergistically increased avenanthramide production in germinating oats to 1505 mg/kg FW. Individual or combined MeJA and ABA treatment increased the expression of genes encoding key catalytic enzymes in the avenanthramide-biosynthesis pathway, including hydroxycinnamoyl-CoA:hydrocyanthranilate N-hydroxycinnamoyl transferase (HHT). Further analyses showed that six AsHHT genes were effectively upregulated by MeJA or ABA treatment, especially AsHHT4 for MeJA and AsHHT5 for ABA, thereby enhancing the production of all three avenanthramides in germinating oats. Specifically, AsHHT5 exhibited the highest expression following MeJA and ABA co-treatment, indicating that AsHHT5 played a more crucial role in avenanthramide biosynthesis in response to MeJA and ABA co-treatment of germinating oats. These findings suggest that elicitor-mediated metabolite farming using MeJA and ABA could be a valuable method for avenanthramide production in germinating oats.
Multi-odor discrimination by rat sniffing for potential monitoring of lung cancer and diabetes
No full textThe discrimination learning of multiple odors, in which multi-odor can be associated with different responses, is important for responding quickly and accurately to changes in the external environment. However, very few studies have been done on multi-odor discrimination by animal sniffing. Herein, we report a novel multi-odor discrimination system by detection rats based on the combination of 2-Choice and Go/No-Go (GNG) tasks into a single paradigm, in which the Go response of GNG was replaced by 2-Choice, for detection of toluene and acetone, which are odor indicators of lung cancer and diabetes, respectively. Three of six trained rats reached performance criterion, in 12 consecutive successful tests within a given set or over 12 sets with a success rate of over 90%. Through a total of 1300 tests, the trained animals (N = 3) showed multi-odor sensing performance with 88% accuracy, 87% sensitivity and 90% specificity. In addition, a dependence of behavior response time on odor concentrations under given concentration conditions was observed, suggesting that the system could be used for quantitative measurements. Furthermore, the animals’ multi-odor sensing performance has lasted for 45 days, indicating long-term stability of the learned multi-odor discrimination. These findings demonstrate that multi-odor discrimination can be achieved by rat sniffing, potentially providing insight into the rapid, accurate and cost-effective multi-odor monitoring in the lung cancer and diabetes.
Impact of bisoprolol on ventricular arrhythmias in experimental myocardial infarction
No full textFollowing acute myocardial infarction (AMI), early use of beta-blockers (BBs) reduced the incidences of ventricular arrhythmia (VA) and death in the pre reperfusion era. However, some studies have reported a worsening of clinical outcomes and therefore, this study used a porcine model of AMI to evaluate the efficacy of bisoprolol on VAs and mortality. Twenty pigs were divided into two groups with one group using oral biso-prolol which was given for 3 hours before the experiment and then maintained for 7 days. A loop recorder was implanted, AMI was induced by balloon occlusion for 60 min, and then, reperfusion. One week later, the echocardiography and loop recorder data were analyzed in the surviving animals. Bisoprolol did not increase the heart rate (62.9±14.5 vs 79.0±20.3; p=0.048), lower the rate of premature ventricular contractions (PVC) (0.8±0.8 vs 11.0±12.8; p=0.021) or tend to lower recurrent VA (0.6±0.5 vs 1.1±1.1; p=0.131) during coronary artery occlusion. After reperfusion, bisoprolol did reduce VA in the early AMI period (0.1±0.3 vs 4.2±4.6; p=0.001) and it was not associated with the extent of myocardial recovery. In this porcine model, early oral bisoprolol might help reduce the incidences of PVC and recurrent VA and determine whether effects are more pronounced during the early AMI period. Our results suggest that bisoprolol might help reduce lethal VA and cardiac death following AMI in this reperfusion era.
Identification of a novel trait associated with phytotoxicity of an insecticide etofenprox in soybean
No full textSynthetic insecticides are widely used to control pests in various crop fields. Especially in soybean [Glycine max (L.) Merr.] fields, the insecticide etofenprox, which is a pyrethroid derivative, has been used to manage hemiptera pests. To date, soybean phytotoxicity response has not been reported to etofenprox derivatives, two Korean cultivars, Danbaek and Kwangan, were first identified to show leaf shape shrinkage damage after etofenprox application. We confirmed that the causal substance for phytotoxicity is etofenprox and that it had dosage effects. Through genetic analysis using three F2 populations, sensitivity to etofenprox is confirmed to be managed by a single dominant gene, and that gene is the same in Danbaek and Kwangan. Although further genetic research is required to identify the gene responsible for sensitivity to etofenprox, the results of this study will help to elucidate the interaction between plants and chemicals when breeding new cultivars or developing pesticides.
Efficacy evaluation of natural products on respiratory diseasesand mechanism study of possible effects of fine dust on respiratory diseases
No full text천연물소재의 호흡기질환 치료효능평가 및 미세먼지 노출이 호흡기질환에 미치는 영향에 대한 기전연구OGM469201
Combination treatment of arazyme and soy leaf extract attenuates hyperglycemia and hepatic steatosis in high-fat diet-fed C57BL/6J mice
No full textArazyme and extracts of soy leaves (ESLs) are used as ingredients for functional foods; however, their combined administration has not been studied. This study assessed the combined effect of Arazyme and ESLs in high-fat-diet (HFD)-induced obese C57BL/6J mice fed 2 mg/kg Arazyme, 50 mg/kg ESLs, or a combination of 2 mg/kg Arazyme and 50 mg/kg ESLs by oral gavage for 13 weeks. Individually, Arazyme and ESLs had no effect on the HFD-induced phenotypes. The combination of Arazyme and ESLs significantly suppressed body weight gain, improved glucose and insulin tolerance, and suppressed hepatic steatosis by reducing lipid synthesis and enhancing lipid utilization gene expression. Furthermore, the combination significantly reduced HFD-induced plasma bile acid reabsorption by suppressing bile acid transporter expression, including the ATP biding cassette subfamily B member 11 (Abcb11), solute carrier family 10 member 1 (Slc10a1), Slc10a2, Slc51a, and Slc51b in the liver and gut. Moreover, the combination of Arazyme and ESLs significantly prevented HFD-induced islet compensation in the pancreas. These results suggest that the incorporation of Arazyme combined with ESLs reduces HFD-induced body weight, hyperglycemia, and hepatic steatosis by regulating liver？gut bile acid circulation in HFD-fed mice. This combination can markedly reduce treatment doses and enhance their therapeutic effects, thereby reducing therapeutic healthcare costs.