This study was conducted in an effort to investigate the effect of Maillard reaction products (MRPs) on enzymatic browning of burdock and their anti-oxidant activity. The MRPs were prepared by heating glucose and amino acids at $90^{\circ}C$, which served to produce a strong inhibitory effect on burdock polyphenol oxidase. As the reaction time of the solution containing glucose and amino acid increased at $90^{\circ}C$, the production of MRPs increased and intensity of the brown color deepened. When MRPs were prepared by heating at $90^{\circ}C$ for five hours, the absorbance of MRPs from glucose and lysine was 6.44, while those of glucose and glycine was 1.95. The MRPs synthesized from the glucose and lysine also reduced the pH of MRPs from 5.60 to 4.51, but those from glucose and glycine decreased slightly from 5.57 to 5.33. The Michealis-Menten constant value ($K_m$) of burdock PPO with pyrocatechol as a substrate was 16.0 mM, and MRPs were a non-competitive inhibitor against burdock PPO. The anti-oxidant activity of MRPs was measured by evaluating its radical scavenging activities of DPPH radicals, ABTS radicals and reducing power. The color intensity of MRPs produced by lysine and glucose were deeper than that produced by glucose and glycine. It was also found that MRPs produced from glucose and lysine exhibited stronger anti-oxidant properties than those produced by glucose and glycine.
In an attempt to examine the ability of benzisothiazole-based drugs to interact with $\beta$-adrenoceptors, a series of 1,2-benzisothiazole derivatives, which were substituted with various propanolamine or oxypropanolamine side chains in the 2 or 3 position, were synthesised and tested. The pharmacological activity of these compounds at the ,$\beta$-adrenoceptors was examined using isolated rat atria and small intestinal segments, which preferentially express the $\beta_{1}$- and $\beta_{3}$-adrenoceptor-mediated responses, respectively. None of these products showed any $\beta$-adrenoceptor agonistic activity. In contrast, the 2- and 3-substituted isopropyl, tert-butyl, benzyl, and piperonyl derivatives 2a-d and 3a-d elicited surmountable inhibition of the isoprenaline-induced chronotropic effects in the atria, suggesting competitive antagonism at the $\beta_{1}$recognition site. The $pA_{2}$ values revealed tert-butyl 3b and the isopropyl substituted piperonyl derivatives 3a to be the most effective. Remarkably, many of the 2-substituted propanolamines were less active than the corresponding 3-substituted oxypropanolamines. With the exception of compound 3b, none of these drugs antagonised the muscle relaxant activity of isoprenaline in the intestine, suggesting no effect on the $\beta_{3}$-adrenoceptors. These results confirm the ability of the benzisothiazole ring to interact with the $\beta$-adrenoceptors, and demonstrate that 2-substitution with propanolamine or 3-substitution with oxypropanolamine groups yields compounds with preferential antagonistic activity at the cardiac $\beta_{1}$adrenoceptors. The degree of antagonism depends strongly on both the nature of the substituent and its position on the benzisothiazole ring.
Park, Jae Eun;Kim, Hyeon Woo;Yun, Sung Hwan;Kim, Sun Jung
Journal of Ginseng Research
/
v.45
no.6
/
pp.754-762
/
2021
Background: Ginsenoside Rh2, a major saponin derivative in ginseng extract, is recognized for its anti-cancer activities. Compared to coding genes, studies on long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) that are regulated by Rh2 in cancer cells, especially on competitive endogenous RNA (ceRNA) are sparse. Methods: LncRNAs whose promoter DNA methylation level was significantly altered by Rh2 were screened from methylation array data. The effect of STXBP5-AS1, miR-4425, and RNF217 on the proliferation and apoptosis of MCF-7 breast cancer cells was monitored in the presence of Rh2 after deregulating the corresponding gene. The ceRNA relationship between STXBP5-AS1 and miR-4425 was examined by measuring the luciferase activity of a recombinant luciferase/STXBP5-AS1 plasmid construct in the presence of mimic miR-4425. Results: Inhibition of STXBP5-AS1 decreased apoptosis but stimulated growth of the MCF-7 cells, suggesting tumor-suppressive activity of the lncRNA. MiR-4425 was identified to have a binding site on STXBP5-AS1 and proven to be downregulated by STXBP5-AS1 as well as by Rh2. In contrast to STXBP5-AS1, miR-4425 showed pro-proliferation activity by inducing a decrease in apoptosis but increased growth of the MCF-7 cells. MiR-4425 decreased luciferase activity from the luciferase/STXBP5-AS1 construct by 26%. Screening the target genes of miR-4425 and Rh2 revealed that Rh2, STXBP5-AS1, and miR-4425 consistently regulated tumor suppressor RNF217 at both the RNA and protein level. Conclusion: LncRNA STXBP5-AS1 is upregulated by Rh2 via promoter hypomethylation and acts as a ceRNA, sponging the oncogenic miR-4425. Therefore, Rh2 controls the STXBP5-AS1/miR-4425/RNF217 axis to suppress breast cancer cell growth.
Jong-Min Park;Young-Min Han;Migyeong Jeong;Eun Jin Go;Napapan Kangwan;Woo Sung Kim;Ki Baik Hahm
Journal of Digestive Cancer Research
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v.4
no.1
/
pp.1-9
/
2016
The abundance of multi-drug resistance ATPase binding cassette and deranged self-renewal pathways shown in cancer stem cells (CSCs) played a crucial role in tumorigenesis, tumor resistance, tumor recurrence, and tumor metastasis. Therefore, elucidation of CSCs biology can improve diagnosis, enable targeted treatment, and guide the follow up of GI cancer patients. In order to achieve chemoquiescence, seizing cancer through complete ablation of CSCs, CSCs are rational targets for the design of interventions that will enhance responsiveness to traditional therapeutic strategies and contribute in the prevention of local recurrence as well as metastasis. However, current cancer treatment strategies fail to either detect or differentiate the CSCs from their non-tumorigenic progenies mostly due to the absence of specific biomarkers and potent agents to kill CSCs. Recent advances in knowledge of CSCs enable to produce several candidates to ablate CSCs in gastrointestinal (GI) cancers, especially cancers originated from inflammation-driven mutagenesis such as Barrett's esophagus (BE), Helicobacter pylori-associated gastric cancer, and colitis-associated cancer (CAC). Our research teams elucidated through revisiting old drugs that proton pump inhibitor (PPI) and potassium competitive acid blocker (p-CAB) beyond authentic acid suppression, chloroquine for autophage inhibition, sonic hedgehog (SHH) inhibitors, and Wnt/β-catenin/NOTCH inhibitor can ablate CSCs specifically and efficiently. Furthermore, nanoformulations of these molecules could provide an additional advantage for more selective targeting of the pathways existing in CSCs just like current molecular targeted therapeutics and sustained action, while normal stem cells intact. In this review article, the novel approach specifically to ablate CSCs existing in GI cancers will be introduced with the introduction of explored mode of action.
Kim, Min-Hae;Chung, Yoo-Taek;Lee, Jin-Ha;Park, Young-Shik;Shin, Myung-Ki;Kim, Ho-Sang;Kim, Dong-Hoon;Lee, Hyeon-Yong
Korean Journal of Medicinal Crop Science
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v.8
no.3
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pp.225-233
/
2000
There was not noticeable differences in decreasing blood alcohol concentrations between Korea and China-produced Hovenia dulcis $T_{HUNB}$, showing only 1-2 % higher decreasing rate for Korea-produced seed extracts than those from China. It was also found that the blood alcohol decreasing ability was greatly enhanced by partitioning the crude extracts produced from both places. The both extracts (crude and partitioned) accelerated the reducing rate of blood alcohol concentrations down to 1-2 hours, compared to that of control (taking only ethanol). The crude extracts from imported seeds seemed to have slightly better effect on improving in vivo ADH and ALDH activities than domestic ones; however, not for partitioned extracts. It was interesting that the partitioned extracts from both countries enhanced ADH enzyme activity up to 60% than the crude, compared to the control, while ALDH activity was not much affected by the partitioned extracts. It was also confirmed that both ADH and ALDH activities were well balanced in controlling blood alcohol concentration maintaining 28-29% of enzyme activities in vivo. The extracts proved to have better effect on enhancing ALDH activity than ADH activity, which is one of possible explanation that Hovenia dulcis $T_{HUNB}$ can effectively relieve the hangover by fast decreasing acetaldehyde concentration in the liver and blood. GST activity was also increased in the range of 120 to 300% by adding crude or partitioned extracts from both countries; however, there was no difference in enhancing GST activity between the extracts from two countries. The extracts showed competitive inhibition with GST activity, showing the reduction of enzyme activity at higher than 0. 6 (g/L) of the imported extracts.
In order to investigate the lowering effects of in vitro enzymatic hydrolysis by the treatment of chymotrypsin, trypsin, pancreatin, or protease from Aspergillus oryzae on the antigenicity of whey protein(WPI) against rabbit anti ${\beta}-LG$ antiserum, competitive inhibition ELISA(cELISA) and passive cutaneous anaphylaxis(PCA) test using guinea pig were performed. The results of cELISA showed that the monovalent antigenicity of the whey protein hydrolysates(WPH) to the antiserum was decreased to $10^{-1.7}{\sim}10^{-4.1}$ and less by the hydrolysis. Especially, the antigenicity of OUP(hydrolysate by protease from Asp. oryzae with preteatment of pepsin) was found almost to be removed. By the heterologous PCA the polyvalent antigenicity of the WPH was decreased to $1/2{\sim}1/128$ and less. Especially, the polyvalent antigenicity of OUN(hydrolysate by protease from Asp. oryzae without preteatments) was found almost to be removed, although OUN did not have so high degree of hydrolysis(DH) or so low monovalent antigenicity (reduced to $10^{-3.2}$). Therefore, this result was assumed to come from effective destruction of antigenic determinants on ${\beta}-LG$ in WPI, not to produce polyvalent antigenic peptides that are closely associated with induction of allergy. This finding suggested that WPH prepared by the treatment of microorganic protease from Asp. oryzae would be a material for hypoallergenic infant formula due to the removal of the polyvalent antigenicity of ${\beta}-LG$, the major milk allergen in WPI.
Monitoring of Listeria monocytogenes, the causative agent of listeriosis, in food is inportant for public health. The Korean Food Standards Codex has adopted a 'zero-tolerance' policy for L. monocytogenes. The standard detection method of L. monocytogenes is based on enrichment. Thus, proper enrichment methods need to be instituted to ensure quality control of the detection procedures. In this study, the growth of L. monocytogenes and Listeria innocua as a mixed culture in Listeria enrichment broth (LEB) was monitored during artificial contamination of enrichment culture. We confirmed competitive growth or interspecies inhibitory activity of L. monocytogenes and L. innocua. Interspecies growth differences and the inhibitory activity of different inoculation and mixtures L. innocua against L. monocytogenes were examined. The concentration of L. monocytogenes must be 2.0 log CFU/mL or more than L. innocua to grow better than L. innocua. It is known that Listeria spp. and L. monocytogenes show growth difference during LEB, resulting in the risk of false-negative results. The inhibition of L. monocytogenes by L. innocua was always observed when present at lower concentrations. However, it was confirmed that L. innocua suppressed when L. monocytogenes was present at a higher concentration. Therefore if a mixture of Listeria spp. is present, detecting L. monocytogenes is difficult. Thus, a new enrichment broth to improve the detection rate of L. monocytogenes is needed.
Park, Eung-Chul;Cho, Yun-Gyoo;Yang, Byung-Hwan;Kim, Kwang-Iel;Yang, Bo-Gee;Chai, Young-Gyu
Korean Journal of Biological Psychiatry
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v.8
no.1
/
pp.85-95
/
2001
This study was designed to examine the effects of two antidepressant drugs on the expression of c-fos mRNA in cultured embryonic rat hippocampal neurons. The drugs used were imipramine and amitriptyline. On the fourth day of culture, hippocampal neurons were treated with variable concentrations of each drug. Competitive RT-PCR(Reverse Transcriptase-PCR) analysis was used to quantify the c-fos mRNA expression induced by each drug. Experimental results showed that acute and direct treatment with imipramine and amitriptyline with relatively low concentrations(imipramine ${\leq}10{\mu}M$, amitriptylne ${\leq}10{\mu}M$) had no inductive effect on the expression of c-fos mRNA in the rat hippocampal neurons. However, after treatment with relatively high concentrations(imipramine ${\geq}100{\mu}M$, amitriptyline ${\geq}100{\mu}M$) c-fos mRNA was not detected. These findings suggest the followings. Firstly, the action mechanisms of these drugs on the hippocampal neurons might not be mediated by c-fos but by other immediate-early genes(IEGs). Secondly, their actions may be mediated indirectly via other areas of the brain. Thirdly, the expression of c-fos might be inhibited by high concentrations of these drugs, or the high concentrations could induce cell death. Finally, though cell death remains to be confirmed, the inhibition of c-fos induction or cell death could play a role in the cognitive impairments known to be adverse effects of some antidepressants. This study is believed to be a first step toward understanding the mechanisms of learning and memory. Further studies are needed to investigate the expression of various IEGs and changes in the hippocampal neurons of rat resulting from chronic treatment with antidepressant drugs.
Kim, Hyoun-Young;Oh, Young-Sook;Kim, Yeong-Kwan;Choi, Sung-Chan
Korean Journal of Microbiology
/
v.34
no.3
/
pp.126-131
/
1998
Reduction of hexavalent chromium to its trivalent form by leachate microorganisms was studied in batch and bench-scale continuous stirred tank reactor. The inoculum was a culture of microorganisms in leachate and capable of providing up to 90% chromate reduction during 72 h batch assay with $20mg\;Cr(VI)\;L^{-1}$ in minimal media containing different levels of leachate (10 to 60%) and glucose (50 to 200 mM). Addition of glucose increased the efficiency of chromate reduction, but adverse effect was observed with increase of leachate probably due to the competitive inhibition between chromate and sulfate ions. The continuous culture experiment was conducted for 124 days using synthetic feed containing different levels of chromate (5 to $65mg\;L^{-1}$) at room temperature. With a hydraulic retention time of 36 h, chromate reduction efficiency was mostly 100% when Cr(VI) concentrations in the reactor were in the range of 5 to $50mg\;L^{-1}$ Specific rate of Cr(VI) removal was calculated as $3.492mg\;g^{-1}\;protein\;h^{-1}$ during the period of 101~124 days from the start-up which showed 81.2% of average reduction efficiency. The results indicate the potential application of using leachate microorganisms for detoxification of hexavalent chromium in various chromium-contaminated wastewater from landfill or tannery sites.
Plant residues serve as substrates for the proliferation and overwintering of plant pathogenic fungi in soil. Effects of the biocontrol fungus Trichoderma harzianum on the colonization of wheat straw by the plant pathogenic fungus Fusarium solani were investigated under different soil moisture regimes (-50 vs. -500 kPa) in non-sterile soil. T. harzianum ThzID1-M3 and/or F. solani were added along with wheat straw to non-sterile soils. ThzID1-M3, other Trichoderma species, and F. solani were monitored for a 21-day period using quantitative PCR. ThzID1-M3 reduced the colonization of F. solani on wheat straw (p < 0.05) under both moisture regimes, and F. solani reduced the colonization by ThzID1-M3 and other Trichoderma species (p < 0.05), thus suggesting competitive inhibition between ThzID1-M3 and F. solani. Colonization by ThzID1-M3 and generic Trichoderma was improved in the wet soil (p < 0.05), but colonization by F. solani did not differ between the two moisture conditions. Thus, the inhibitory effect of ThzID1-M3 was greater in the wet soil (p < 0.05). The growth competition between ThzID1-M3 and F. solani to colonize plant debris suggests that the biocontrol fungus T. harzianum may reduce the potential of the plant pathogen, F. solani, to survive and proliferate on crops.
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