Sa-Hyun Kim - Academia.edu (original) (raw)

Papers by Sa-Hyun Kim

Current Issues in Molecular Biology

Evodiamine isolated from Evodia rutaecarpa has been known to have anti-tumor activity against var... more Evodiamine isolated from Evodia rutaecarpa has been known to have anti-tumor activity against various cancer cell types. Although there have been reports showing the inhibitory effect of evodiamine on cell survival of gastric cancer cell, it is not clearly explained how evodiamine affects the expression and modification of proteins associated with apoptosis and upstream signal pathways. We confirmed the cytotoxic activity of evodiamine against AGS and MKN45 cells by a WST assay, cell morphological change, and clonogenic assay. The apoptotic cells were evaluated by Annexin V/PI analysis and Western blot and the expressions of apoptosis-related molecules were confirmed by Western blot. Evodiamine promoted apoptosis of AGS gastric cancer cells through both intrinsic and extrinsic signal pathways in a time- and dose-dependent manner. Evodiamine attenuated the expression of anti-apoptotic proteins, including Bcl-2, XIAP, and survivin, and elevated that of the pro-apoptotic protein Bax. E...

Molecules, 2021

Extracts from barley seedlings (BS) have known antioxidant and anti-inflammatory activities. The ... more Extracts from barley seedlings (BS) have known antioxidant and anti-inflammatory activities. The flavonoid lutonarin (LN) is a component of BS extract and has several known bioactivities. Here, we evaluated LN anti-inflammatory efficacy against lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Lutonarin was isolated from BS by methanol extraction and characterized by ultra-performance liquid chromatography and quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS). Lutonarin did not reduce the viability or enhance the apoptosis rate of RAW 264.7 macrophages at concentrations up to 150 µM. Concentrations within 20–60 µM dose-dependently suppressed the LPS-induced expression, phosphorylation, and nuclear translocation of the inflammatory transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Furthermore, LN suppressed the LPS-induced upregulation of proinflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF...

Helicobacter pylori primarily colonizes in the human stomach and induces various gastric diseases... more Helicobacter pylori primarily colonizes in the human stomach and induces various gastric diseases, including gastric cancer. H. pylori utilizes various bacterial proteins, such as toxins, ureases, and adhesion and flagella proteins, for successful colonization and pathogenesis. In particular, urease is an indispensable virulence factor for the pathogenesis and survival of H. pylori in the acidic conditions of the stomach. In this study, therefore, we investigated the anti-urease activity of a natural compound, plumbagin, and found that it inhibited urease activity of various urease-producing bacteria. We determined the minimal inhibitory concentration of plumbagin against H. pylori, and demonstrated the inhibitory effect of plumbagin on H. pylori urease by using a urease activity assay. The inhibitory effect of plumbagin on urease was confirmed by using purified jack bean urease as the reference molecule, with acetohydroxamic acid as the reference inhibitor. Furthermore, we also con...

The Korean Journal of Clinical Laboratory Science, 2019

Menadione is known as an anti-tumor factor. Many studies have reported the potential anti-cancer ... more Menadione is known as an anti-tumor factor. Many studies have reported the potential anti-cancer role of menadione against a range of cancer cell lines. In this study, the anti-cancer effects of menadione and the underlying molecular signaling involved in apoptosis was investigated in gastric cancer cell lines. The menadione treatment decreased the cell viability of MKN45 gastric cancer cells. The decreased cell viability was attributed to the induction of apoptosis, which was confirmed by the results indicating the activation of caspase-3 and-7 and the cleavage of PARP in Western blotting. The upstream regulatory molecules involved in apoptosis were investigated further and it was discovered that menadione reduced the expression of survivin, an inhibitor of upstream apoptosis proteins. In addition, a transcription factor -catenin, which is known to regulate survivin expression, was down-regulated by menadione. A previous report showed that menadione inhibited XIAP expression to induce apoptosis and induced G2/M cell cycle arrest in AGS cells. This study elucidated another inhibitory mechanism of menadione against gastric cancer cells in a different cell line. Although further studies will be needed, the inhibitory mechanism demonstrated in this study will help better understand the anti-cancer effects of menadione.

The Korean Journal of Clinical Laboratory Science, 2017

Zerumbone is a major component of the essential oil from Zingiber zerumbet Smith, which is a kind... more Zerumbone is a major component of the essential oil from Zingiber zerumbet Smith, which is a kind of wild ginger. In addition, various biological functions, such as liver protection, pain relief, atherosclerosis, and antimicrobial activity have been reported. It is also known to be effective in the proliferation of immune cells and the expression of cytokines. In this study, we investigated the effects of zerumbone on monocyte activation. First, it was confirmed that the proliferation of THP-1 cells was increased by zerumbone. The strongest increase in THP-1 proliferation after lipopolysaccharide treatment was observed at 5 M zerumbone treatment, and the increase of cell proliferation without lipopolysaccharide was the highest at 10 M. Conversely, when treated with 50 M zerumbone, a rapid decrease of proliferation was observed regardless of the presence of lipopolysaccharide (LPS). The phosphorylation of signaling protein, Erk, induced by LPS was also increased by zerumbone. The strongest increase in phosphorylation was observed when treated with 50 M of zerumbone with reduced proliferation. The activity of transcription factor NF-B was not significantly altered by zerumbone alone, but increased when treated with lipopolysaccharide. Furthermore, the transcription of the inflammatory cytokines TNF- and IL-8, which are regulated by NF-B, is also increased by zerumbone. These results suggest that zerumbone can enhance the proliferation and activity of monocytes. Furthermore, it is believed that zerumbone can enhance rthe immune responses through increased monocyte activity in bacterial infections with LPS, thereby helping to treat effective bacteria.

American journal of translational research, 2016

Menadione (vitamin K3) has been reported to induce apoptotic cell death and growth inhibition in ... more Menadione (vitamin K3) has been reported to induce apoptotic cell death and growth inhibition in various types of cancer cells. However, involvement of menadione in cell cycle control has not been considered in gastric cancer cells yet. In the current study, we have investigated whether menadione is involved in the cell cycle regulation and suppression of growth in gastric cancer cells. In the cell cycle analysis, we found that menadione induced G2/M cell cycle arrest in AGS cells. To elucidate the underlying mechanism, we investigated the cell cycle regulatory molecules involved in the G2/M cell cycle transition. After 24 h of menadione treatment, the protein level of CDK1, CDC25C and cyclin B1 in AGS cells was decreased in a menadione dose-dependent manner. In the time course experiment, the protein level of CDC25C decreased in 6 h, and CDK1and cyclin B1 protein levels began to decrease after 18 h of menadione treatment. We found that mRNA level of CDC25C decreased by menadione tr...

The Korean Journal of Helicobacter and Upper Gastrointestinal Research, 2014

International Journal of Antimicrobial Agents, 2012

Acinetobacter baumannii is an increasingly important nosocomial pathogen, frequently causing noso... more Acinetobacter baumannii is an increasingly important nosocomial pathogen, frequently causing nosocomial outbreaks in hospital Intensive Care Units. Infections caused by multidrugresistant (MDR) bacteria occur worldwide. Furthermore, A. baumannii strains resistant to all antimicrobial agents tested, susceptible only to colistin, are referred to as extensively drugresistant strains and have been detected in South Korea [1]. The purpose of this study was to determine the genetic basis and molecular epidemiology of MDR A. baumannii isolates and to determine the clonal relationship amongst A. baumannii clinical isolates obtained from Gangwon Province, South Korea. The various molecular determinants of A. baumannii, including carbapenem, cephalosporin, aminoglycoside and quinolone resistance, were investigated in this study. Eighty-six strains of non-duplicate A. baumannii were identified by MicroScan WalkAway-96 (Dade Behring, Sacramento, CA) as belonging to Acinetobacter baumannii/haemolyticus from the university hospital laboratory in Gangwon Province from July 2007 to July 2010. Genomic identification was performed using the amplified ribosomal DNA restriction analysis (ARDRA) method [2]. The experimental results revealed that all strains tested were A. baumannii. Minimum inhibitory concentrations of clinical antimicrobials for all isolates were determined by the MicroScan WalkAway-96 AI system and were interpreted according to Clinical and Laboratory Standards Institute (CLSI) document M100-S19. All of the isolates showed resistance to ampicillin, cefazolin, cefotaxime, cefotetan, ceftazidime, ceftriaxone, cefuroxime, ciprofloxacin, meropenem, moxifloxacin and ticarcillin/clavulanic acid. Moreover, most of A. baumannii isolates showed resistance to cefepime, gentamicin, trimethoprim/sulfamethoxazole, tobramycin, aztreonam, amikacin, imipenem and ampicillin/sulbactam. To analyse the production of class B and D carbapenemases, A. baumannii isolates were first screened by a modified Hodge test [3]. All of the A. baumannii isolates showed positive results in the modified Hodge test and negative results in the ethylene diamine tetra-acetic acid (EDTA) disk synergy test, indicating the production of class D or another type of carbapenemase. The ␤-lactamases and resistance determinants were detected by multiplex polymerase chain reaction (PCR) [4]. The presence of insertion sequence ISAba1 inserted upstream of bla OXA-23-like and bla OXA-51-like was sought via PCR using combinations of the ISAba1 primers and the OXA-23-like and OXA-51-like reverse primers [4]. All of the isolates possessed the encoded gene for an intrinsic OXA-51-like carbapenemase and an acquired OXA-23-like carbapenemase. ISAba1 inserted upstream of bla OXA-23-like was identified in all of the A. baumannii isolates.

International Journal of Molecular Sciences, 2021

Helicobacter pylori (H. pylori) is a bacterium known to infect the human stomach. It can cause va... more Helicobacter pylori (H. pylori) is a bacterium known to infect the human stomach. It can cause various gastrointestinal diseases including gastritis and gastric cancer. Hesperetin is a major flavanone component contained in citrus fruits. It has been reported to possess antibacterial, antioxidant, and anticancer effects. However, the antibacterial mechanism of hesperetin against H. pylori has not been reported yet. Therefore, the objective of this study was to determine the inhibitory effects of hesperetin on H. pylori growth and its inhibitory mechanisms. The results of this study showed that hesperetin inhibits the growth of H. pylori reference strains and clinical isolates. Hesperetin inhibits the expression of genes in replication (dnaE, dnaN, dnaQ, and holB) and transcription (rpoA, rpoB, rpoD, and rpoN) machineries of H. pylori. Hesperetin also inhibits the expression of genes related to H. pylori motility (flhA, flaA, and flgE) and adhesion (sabA, alpA, alpB, hpaA, and hopZ)....

International Journal of Molecular Sciences, 2021

Helicobacter pylori (H. pylori) classified as a class I carcinogen by the World Health Organizati... more Helicobacter pylori (H. pylori) classified as a class I carcinogen by the World Health Organization (WHO) plays an important role in the progression of chronic gastritis and the development of gastric cancer. A major bioactive component of Evodia rutaecarpa, evodiamine, has been known for its anti-bacterial effect and anti-cancer effects. However, the inhibitory effect of evodiamine against H. pylori is not yet known and the inhibitory mechanisms of evodiamine against gastric cancer cells are yet to be elucidated concretely. In this study, therefore, anti-bacterial effect of evodiamine on H. pylori growth and its inhibitory mechanisms as well as anti-inflammatory effects and its mechanisms of evodiamine on H. pylori-induced inflammation were investigated in vitr. Results of this study showed the growth of the H. pylori reference strains and clinical isolates were inhibited by evodiamine. It was considered one of the inhibitory mechanisms that evodiamine downregulated both gene expre...

Recent studies have reported menadione (vitamin K3) has inhibitory effect on several types of can... more Recent studies have reported menadione (vitamin K3) has inhibitory effect on several types of cancer cells including lung cancer, breast cancer, ovarian cancer, pancreatic cancer and hepatocellular carcinoma, although the effect of menadione on gastric cancer cells is unclear. Therefore, we have investigated the inhibitory effect and the mechanism of menadione on gastric cancer cells. We found that cell viability of AGS (gastric cancer cell) was dramatically inhibited by menadione, while HS738 (non-cancerous gastrointestinal cell) was not influenced by the same dose of menadione treatment. Annexin V-FITC assay results suggested that decreased cell viability was due to the induction of apoptosis and it was confirmed by the results indicating activation of caspase-3 and caspase-9 and cleavage of PARP in the Westernblot. We further investigated the upstream regulatory molecules involved in the apoptosis and discovered that manadione reduces expression of X-linked inhibitor of apoptosis...

Molecules, 2021

Helicobacter pylori (H. pylori) produces urease in order to improve its settlement and growth in ... more Helicobacter pylori (H. pylori) produces urease in order to improve its settlement and growth in the human gastric epithelium. Urease inhibitors likely represent potentially powerful therapeutics for treating H. pylori; however, their instability and toxicity have proven problematic in human clinical trials. In this study, we investigate the ability of a natural compound extracted from Zingiber zerumbet Smith, zerumbone, to inhibit the urease activity of H. pylori by formation of urease dimers, trimers, or tetramers. As an oxygen atom possesses stronger electronegativity than the first carbon atom bonded to it, in the zerumbone structure, the neighboring second carbon atom shows a relatively negative charge (δ−) and the next carbon atom shows a positive charge (δ+), sequentially. Due to this electrical gradient, it is possible that H. pylori urease with its negative charges (such as thiol radicals) might bind to the β-position carbon of zerumbone. Our results show that zerumbone dim...

H. pylori is a Gram-negative curved bacterium which primarily colonizes the epithelial layer of h... more H. pylori is a Gram-negative curved bacterium which primarily colonizes the epithelial layer of human stomach. Infection with this bacterium may lead to various gastric diseases from asymptomatic gastritis to gastric cancer. Because of its clinical importance, WHO designated H. pylori as a class I carcinogen. Kinetin is a type of cytokinins major role of which is to facilitate growth of the plants but it also plays a role to protect plants from infections. However, anti-bacterial effect of kinetin on H. pylori has not been elucidated. In this study, we performed agar dilution test and broth dilution test to determine MIC of kinetin against an H. pylori reference strain. In particular, we isolated H. pylori from gastric biopsies and confirmed inhibitory effect of kinetin against 60 clinical isolates of H. pylori. To elucidate the inhibitory mechanism of kinetin on H. pylori growth, we performed RT-PCR and found that kinetin down-regulated dnaA and holB expression both of which are ne...

Urinary tract infection (UTI) is one of the most common bacterial infections and is predominantly... more Urinary tract infection (UTI) is one of the most common bacterial infections and is predominantly caused by uropathogenic Escherichia coli (UPEC). UPEC strains generally possess several genes encoding virulent factors, which are mostly adhesins, toxins, bacteriocin and siderophores. E. coli is composed of four main phylogenetic group (A, B1, B2, D) and virulent extra-intestinal strains mainly belong to groups B2 and D. Prescription of ciprofloxacin, a kind of fluoroquinolone group antibiotics, is increasing now a days, but resistance to this drug is also increasing. A total of 188 strains of E. coli were collected. Thirteen strains were collected from healthy students in 2011 and 175 strains from patients with urinary tract infection in 2010. Virulence factor genes (papC, fimG/H, sfaD/E, hlyA, cnf1, and usp) were amplified by polymerase chain reaction (PCR) methods for phylogenetic group (A, B1, B2, D) detection. Ciprofloxacin susceptibility test was performed by disk diffusion meth...

Biomedical Science Letters, 2020

Ingestion of food contaminated with microorganism, if not always, could lead to severe health pro... more Ingestion of food contaminated with microorganism, if not always, could lead to severe health problem. Preservatives has been added to food to prevent food from being contaminated with microorganism. But, these have potential to threaten the health. Therefore, much effort has been taken to find the safe materials showing the anti-microbial activity. In this study, we investigated the anti-bacterial activity of Oenothera lamarckiana aerial part extract against eight bacteria strain. In paper disc assay, extract inhibited the growth of Staphylococcus aureus, Methicillin-resistant S. aureus, Bacillus cereus and Shigella dysenteriae at 200 μg/disc, but not against Escherichia coli, E. coli O157:H7, Salmonella Typhi and S. enteritidis. Minimum inhibitory concentration (MIC) against Staphylococcus aureus, Methicillin-resistant S. aureus, Bacillus cereus and Shigella dysenteriae is 250, 250, 500 and 500 μg/mL, respectively. Compared with reported MIC of other plant resources, O. lamarckiana aerial part extract showed the relatively high anti-bacterial activity. O. lamarckiana aerial part could be suitable for the preservative development. But, it still remains to be studied to evaluate safety and so on.

The Korean Journal of Gastroenterology, 2019

Background/Aims: Helicobacter pylori (H. pylori) infections, which cause a variety of gastrointes... more Background/Aims: Helicobacter pylori (H. pylori) infections, which cause a variety of gastrointestinal symptoms, are common in South Korea. Recent reports have shown a decline in the H. pylori eradication rates. β-caryophyllene is a natural bicyclic sesquiterpene that occurs in a wide range of plant species, such as cloves, basil, and cinnamon. β-caryophyllene has been reported to have anti-inflammatory and anti-bacterial effects. This study investigated the inhibitory effects of β-caryophyllene on H. pylori and its potential role as an alternative gastrointestinal drug. Methods: This 8-week, randomized double-blind, placebo-controlled trial categorized subjects into a β-caryophyllene group (33 patients who received 126 mg/day of β-caryophyllene) and a placebo group (33 patients who received a placebo preparation). The inflammation level of H. pylori infiltration and the eradication rates were evaluated endoscopically and with the urea breath test (UBT) in both groups before and after administering the medication. The serum cytokine levels (tumor necrosis factor-α, and interleukin [IL]-1β and IL-6) were compared in both groups before and after administering the medication. Results: Complete eradication was not observed in either group. Moreover, there was no significant change in the UBT and updated Sydney score. On the other hand, the β-caryophyllene group showed significant improvement in nausea (p=0.025) and epigastric pain (p=0.018), as well as a decrease in the serum IL-1β levels (p=0.038). Conclusions: β-caryophyllene improves dyspepsia symptoms and can be considered a useful supplementary treatment for gastrointestinal disease.

The Korean Journal of Clinical Laboratory Science, 2018

This study examined the effects of zerumbone on monocyte migration. Monocytes are recognized as i... more This study examined the effects of zerumbone on monocyte migration. Monocytes are recognized as important mediators of various inflammatory diseases, and the possibility of controlling inflammatory diseases by regulating the monocyte functions, such as activity and mobility, has been reported. MCP-1, which is a chemokine with levels that increase upon inflammation, causes the migration of the monocyte cell line, THP-1. Migration occurred at a concentration of 10 ng/mL MCP-1, and the highest migration occurred at 100 ng/mL and 200 ng/mL. MCP-1-induced THP-1 migration decreased by more than 40% in the presence of zerumbone. The concentration of cAMP, an important secondary messenger of the CCR2 signaling pathway, the MCP-1 receptor, was increased in the culture medium after a zerumbone treatment. The concentrations of cAMP decreased significantly under the MCP-1 treatment condition only. On the other hand, an increase in cAMP was observed when zerumbone and MCP-1 were treated simultaneously. Erk phosphorylation induced by an MCP-1 treatment was also found to decrease with the zerumbone treatment. This study introduces the possibility of controlling inflammatory diseases through the function of zerumbone, which regulates the migration of monocytes.

International Journal of Molecular Sciences, 2019

H. pylori is classified as a group I carcinogen by WHO because of its involvement in gastric canc... more H. pylori is classified as a group I carcinogen by WHO because of its involvement in gastric cancer development. Several reports have suggested anti-bacterial effects of menadione, although the effect of menadione on major virulence factors of H. pylori and H. pylori-induced inflammation is yet to be elucidated. In this study, therefore, we demonstrated that menadione has anti-H. pylori and anti-inflammatory effects. Menadione inhibited growth of H. pylori reference strains and clinical isolates. Menadione reduced expression of vacA in H. pylori, and translocation of VacA protein into AGS (gastric adenocarcinoma cell) was also decreased by menadione treatment. This result was concordant with decreased apoptosis in AGS cells infected with H. pylori. Moreover, cytotoxin-associated protein A (CagA) translocation into H. pylori-infected AGS cells was also decreased by menadione. Menadione inhibited expression of several type IV secretion system (T4SS) components, including virB2, virB7,...

Bioscience, biotechnology, and biochemistry, Jan 5, 2018

Inflammation induced by Helicobacter pylori infection related to gastric carcinogenesis. In this ... more Inflammation induced by Helicobacter pylori infection related to gastric carcinogenesis. In this study, we have investigated the anti-inflammatory effect and its mechanism of kaempferol in the inflammatory response caused by H. pylori infection in vitro. We found that kaempferol reduced the expression of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-8) and production of IL-8 in AGS cells. In addition, kaempferol suppressed translocation of cytotoxin-associated gene A (CagA) and vacuolating cytotoxin A (VacA) of H. pylori to AGS cells. It was due to decreased transcription of type IV secretion system (T4SS) components involved in CagA injection and secretion system subunit protein A (SecA) of type V secretion system (T5SS) involved in VacA secretion by kaempferol. In conclusion, kaempferol shows the anti-inflammatory effect by suppressing the translocation of CagA and VacA proteins and leading to the down-regulation of pro-inflammatory cytokines. CagA: cytotoxin-associated gene A;...

Molecular nutrition & food research, Feb 16, 2017

Black rice extract (BRE) contains cyanidin 3-O-glucoside (C3G), an anthocyanin, as the major comp... more Black rice extract (BRE) contains cyanidin 3-O-glucoside (C3G), an anthocyanin, as the major component. In this study, we found that BRE inhibited the mRNA and protein expression of genes encoding cytotoxin-associated protein A (cagA) and vacuolating protein A (vacA) in Helicobacter pylori 60190 strain. We performed RT-PCR and western blotting to show that BRE inhibited the mRNA and protein expression of SecA. Because SecA is involved in VacA export in bacteria, our result suggested a positive correlation between BRE-induced inhibition of secA expression and VacA secretion. Further, we performed MTT assay and flow cytometry to show that BRE decreased the apoptosis of H. pylori-infected KATO III cells. Finally, we performed western blotting to show that the cell-protective effect of BRE was associated with decreased levels of active proapoptotic proteins caspases and PARP and increased levels of antiapoptotic proteins survivin and XIAP in H. pylori-infected cells. Thus, our results i...

Current Issues in Molecular Biology

Evodiamine isolated from Evodia rutaecarpa has been known to have anti-tumor activity against var... more Evodiamine isolated from Evodia rutaecarpa has been known to have anti-tumor activity against various cancer cell types. Although there have been reports showing the inhibitory effect of evodiamine on cell survival of gastric cancer cell, it is not clearly explained how evodiamine affects the expression and modification of proteins associated with apoptosis and upstream signal pathways. We confirmed the cytotoxic activity of evodiamine against AGS and MKN45 cells by a WST assay, cell morphological change, and clonogenic assay. The apoptotic cells were evaluated by Annexin V/PI analysis and Western blot and the expressions of apoptosis-related molecules were confirmed by Western blot. Evodiamine promoted apoptosis of AGS gastric cancer cells through both intrinsic and extrinsic signal pathways in a time- and dose-dependent manner. Evodiamine attenuated the expression of anti-apoptotic proteins, including Bcl-2, XIAP, and survivin, and elevated that of the pro-apoptotic protein Bax. E...

Molecules, 2021

Extracts from barley seedlings (BS) have known antioxidant and anti-inflammatory activities. The ... more Extracts from barley seedlings (BS) have known antioxidant and anti-inflammatory activities. The flavonoid lutonarin (LN) is a component of BS extract and has several known bioactivities. Here, we evaluated LN anti-inflammatory efficacy against lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Lutonarin was isolated from BS by methanol extraction and characterized by ultra-performance liquid chromatography and quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS). Lutonarin did not reduce the viability or enhance the apoptosis rate of RAW 264.7 macrophages at concentrations up to 150 µM. Concentrations within 20–60 µM dose-dependently suppressed the LPS-induced expression, phosphorylation, and nuclear translocation of the inflammatory transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Furthermore, LN suppressed the LPS-induced upregulation of proinflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF...

Helicobacter pylori primarily colonizes in the human stomach and induces various gastric diseases... more Helicobacter pylori primarily colonizes in the human stomach and induces various gastric diseases, including gastric cancer. H. pylori utilizes various bacterial proteins, such as toxins, ureases, and adhesion and flagella proteins, for successful colonization and pathogenesis. In particular, urease is an indispensable virulence factor for the pathogenesis and survival of H. pylori in the acidic conditions of the stomach. In this study, therefore, we investigated the anti-urease activity of a natural compound, plumbagin, and found that it inhibited urease activity of various urease-producing bacteria. We determined the minimal inhibitory concentration of plumbagin against H. pylori, and demonstrated the inhibitory effect of plumbagin on H. pylori urease by using a urease activity assay. The inhibitory effect of plumbagin on urease was confirmed by using purified jack bean urease as the reference molecule, with acetohydroxamic acid as the reference inhibitor. Furthermore, we also con...

The Korean Journal of Clinical Laboratory Science, 2019

Menadione is known as an anti-tumor factor. Many studies have reported the potential anti-cancer ... more Menadione is known as an anti-tumor factor. Many studies have reported the potential anti-cancer role of menadione against a range of cancer cell lines. In this study, the anti-cancer effects of menadione and the underlying molecular signaling involved in apoptosis was investigated in gastric cancer cell lines. The menadione treatment decreased the cell viability of MKN45 gastric cancer cells. The decreased cell viability was attributed to the induction of apoptosis, which was confirmed by the results indicating the activation of caspase-3 and-7 and the cleavage of PARP in Western blotting. The upstream regulatory molecules involved in apoptosis were investigated further and it was discovered that menadione reduced the expression of survivin, an inhibitor of upstream apoptosis proteins. In addition, a transcription factor -catenin, which is known to regulate survivin expression, was down-regulated by menadione. A previous report showed that menadione inhibited XIAP expression to induce apoptosis and induced G2/M cell cycle arrest in AGS cells. This study elucidated another inhibitory mechanism of menadione against gastric cancer cells in a different cell line. Although further studies will be needed, the inhibitory mechanism demonstrated in this study will help better understand the anti-cancer effects of menadione.

The Korean Journal of Clinical Laboratory Science, 2017

Zerumbone is a major component of the essential oil from Zingiber zerumbet Smith, which is a kind... more Zerumbone is a major component of the essential oil from Zingiber zerumbet Smith, which is a kind of wild ginger. In addition, various biological functions, such as liver protection, pain relief, atherosclerosis, and antimicrobial activity have been reported. It is also known to be effective in the proliferation of immune cells and the expression of cytokines. In this study, we investigated the effects of zerumbone on monocyte activation. First, it was confirmed that the proliferation of THP-1 cells was increased by zerumbone. The strongest increase in THP-1 proliferation after lipopolysaccharide treatment was observed at 5 M zerumbone treatment, and the increase of cell proliferation without lipopolysaccharide was the highest at 10 M. Conversely, when treated with 50 M zerumbone, a rapid decrease of proliferation was observed regardless of the presence of lipopolysaccharide (LPS). The phosphorylation of signaling protein, Erk, induced by LPS was also increased by zerumbone. The strongest increase in phosphorylation was observed when treated with 50 M of zerumbone with reduced proliferation. The activity of transcription factor NF-B was not significantly altered by zerumbone alone, but increased when treated with lipopolysaccharide. Furthermore, the transcription of the inflammatory cytokines TNF- and IL-8, which are regulated by NF-B, is also increased by zerumbone. These results suggest that zerumbone can enhance the proliferation and activity of monocytes. Furthermore, it is believed that zerumbone can enhance rthe immune responses through increased monocyte activity in bacterial infections with LPS, thereby helping to treat effective bacteria.

American journal of translational research, 2016

Menadione (vitamin K3) has been reported to induce apoptotic cell death and growth inhibition in ... more Menadione (vitamin K3) has been reported to induce apoptotic cell death and growth inhibition in various types of cancer cells. However, involvement of menadione in cell cycle control has not been considered in gastric cancer cells yet. In the current study, we have investigated whether menadione is involved in the cell cycle regulation and suppression of growth in gastric cancer cells. In the cell cycle analysis, we found that menadione induced G2/M cell cycle arrest in AGS cells. To elucidate the underlying mechanism, we investigated the cell cycle regulatory molecules involved in the G2/M cell cycle transition. After 24 h of menadione treatment, the protein level of CDK1, CDC25C and cyclin B1 in AGS cells was decreased in a menadione dose-dependent manner. In the time course experiment, the protein level of CDC25C decreased in 6 h, and CDK1and cyclin B1 protein levels began to decrease after 18 h of menadione treatment. We found that mRNA level of CDC25C decreased by menadione tr...

The Korean Journal of Helicobacter and Upper Gastrointestinal Research, 2014

International Journal of Antimicrobial Agents, 2012

Acinetobacter baumannii is an increasingly important nosocomial pathogen, frequently causing noso... more Acinetobacter baumannii is an increasingly important nosocomial pathogen, frequently causing nosocomial outbreaks in hospital Intensive Care Units. Infections caused by multidrugresistant (MDR) bacteria occur worldwide. Furthermore, A. baumannii strains resistant to all antimicrobial agents tested, susceptible only to colistin, are referred to as extensively drugresistant strains and have been detected in South Korea [1]. The purpose of this study was to determine the genetic basis and molecular epidemiology of MDR A. baumannii isolates and to determine the clonal relationship amongst A. baumannii clinical isolates obtained from Gangwon Province, South Korea. The various molecular determinants of A. baumannii, including carbapenem, cephalosporin, aminoglycoside and quinolone resistance, were investigated in this study. Eighty-six strains of non-duplicate A. baumannii were identified by MicroScan WalkAway-96 (Dade Behring, Sacramento, CA) as belonging to Acinetobacter baumannii/haemolyticus from the university hospital laboratory in Gangwon Province from July 2007 to July 2010. Genomic identification was performed using the amplified ribosomal DNA restriction analysis (ARDRA) method [2]. The experimental results revealed that all strains tested were A. baumannii. Minimum inhibitory concentrations of clinical antimicrobials for all isolates were determined by the MicroScan WalkAway-96 AI system and were interpreted according to Clinical and Laboratory Standards Institute (CLSI) document M100-S19. All of the isolates showed resistance to ampicillin, cefazolin, cefotaxime, cefotetan, ceftazidime, ceftriaxone, cefuroxime, ciprofloxacin, meropenem, moxifloxacin and ticarcillin/clavulanic acid. Moreover, most of A. baumannii isolates showed resistance to cefepime, gentamicin, trimethoprim/sulfamethoxazole, tobramycin, aztreonam, amikacin, imipenem and ampicillin/sulbactam. To analyse the production of class B and D carbapenemases, A. baumannii isolates were first screened by a modified Hodge test [3]. All of the A. baumannii isolates showed positive results in the modified Hodge test and negative results in the ethylene diamine tetra-acetic acid (EDTA) disk synergy test, indicating the production of class D or another type of carbapenemase. The ␤-lactamases and resistance determinants were detected by multiplex polymerase chain reaction (PCR) [4]. The presence of insertion sequence ISAba1 inserted upstream of bla OXA-23-like and bla OXA-51-like was sought via PCR using combinations of the ISAba1 primers and the OXA-23-like and OXA-51-like reverse primers [4]. All of the isolates possessed the encoded gene for an intrinsic OXA-51-like carbapenemase and an acquired OXA-23-like carbapenemase. ISAba1 inserted upstream of bla OXA-23-like was identified in all of the A. baumannii isolates.

International Journal of Molecular Sciences, 2021

Helicobacter pylori (H. pylori) is a bacterium known to infect the human stomach. It can cause va... more Helicobacter pylori (H. pylori) is a bacterium known to infect the human stomach. It can cause various gastrointestinal diseases including gastritis and gastric cancer. Hesperetin is a major flavanone component contained in citrus fruits. It has been reported to possess antibacterial, antioxidant, and anticancer effects. However, the antibacterial mechanism of hesperetin against H. pylori has not been reported yet. Therefore, the objective of this study was to determine the inhibitory effects of hesperetin on H. pylori growth and its inhibitory mechanisms. The results of this study showed that hesperetin inhibits the growth of H. pylori reference strains and clinical isolates. Hesperetin inhibits the expression of genes in replication (dnaE, dnaN, dnaQ, and holB) and transcription (rpoA, rpoB, rpoD, and rpoN) machineries of H. pylori. Hesperetin also inhibits the expression of genes related to H. pylori motility (flhA, flaA, and flgE) and adhesion (sabA, alpA, alpB, hpaA, and hopZ)....

International Journal of Molecular Sciences, 2021

Helicobacter pylori (H. pylori) classified as a class I carcinogen by the World Health Organizati... more Helicobacter pylori (H. pylori) classified as a class I carcinogen by the World Health Organization (WHO) plays an important role in the progression of chronic gastritis and the development of gastric cancer. A major bioactive component of Evodia rutaecarpa, evodiamine, has been known for its anti-bacterial effect and anti-cancer effects. However, the inhibitory effect of evodiamine against H. pylori is not yet known and the inhibitory mechanisms of evodiamine against gastric cancer cells are yet to be elucidated concretely. In this study, therefore, anti-bacterial effect of evodiamine on H. pylori growth and its inhibitory mechanisms as well as anti-inflammatory effects and its mechanisms of evodiamine on H. pylori-induced inflammation were investigated in vitr. Results of this study showed the growth of the H. pylori reference strains and clinical isolates were inhibited by evodiamine. It was considered one of the inhibitory mechanisms that evodiamine downregulated both gene expre...

Recent studies have reported menadione (vitamin K3) has inhibitory effect on several types of can... more Recent studies have reported menadione (vitamin K3) has inhibitory effect on several types of cancer cells including lung cancer, breast cancer, ovarian cancer, pancreatic cancer and hepatocellular carcinoma, although the effect of menadione on gastric cancer cells is unclear. Therefore, we have investigated the inhibitory effect and the mechanism of menadione on gastric cancer cells. We found that cell viability of AGS (gastric cancer cell) was dramatically inhibited by menadione, while HS738 (non-cancerous gastrointestinal cell) was not influenced by the same dose of menadione treatment. Annexin V-FITC assay results suggested that decreased cell viability was due to the induction of apoptosis and it was confirmed by the results indicating activation of caspase-3 and caspase-9 and cleavage of PARP in the Westernblot. We further investigated the upstream regulatory molecules involved in the apoptosis and discovered that manadione reduces expression of X-linked inhibitor of apoptosis...

Molecules, 2021

Helicobacter pylori (H. pylori) produces urease in order to improve its settlement and growth in ... more Helicobacter pylori (H. pylori) produces urease in order to improve its settlement and growth in the human gastric epithelium. Urease inhibitors likely represent potentially powerful therapeutics for treating H. pylori; however, their instability and toxicity have proven problematic in human clinical trials. In this study, we investigate the ability of a natural compound extracted from Zingiber zerumbet Smith, zerumbone, to inhibit the urease activity of H. pylori by formation of urease dimers, trimers, or tetramers. As an oxygen atom possesses stronger electronegativity than the first carbon atom bonded to it, in the zerumbone structure, the neighboring second carbon atom shows a relatively negative charge (δ−) and the next carbon atom shows a positive charge (δ+), sequentially. Due to this electrical gradient, it is possible that H. pylori urease with its negative charges (such as thiol radicals) might bind to the β-position carbon of zerumbone. Our results show that zerumbone dim...

H. pylori is a Gram-negative curved bacterium which primarily colonizes the epithelial layer of h... more H. pylori is a Gram-negative curved bacterium which primarily colonizes the epithelial layer of human stomach. Infection with this bacterium may lead to various gastric diseases from asymptomatic gastritis to gastric cancer. Because of its clinical importance, WHO designated H. pylori as a class I carcinogen. Kinetin is a type of cytokinins major role of which is to facilitate growth of the plants but it also plays a role to protect plants from infections. However, anti-bacterial effect of kinetin on H. pylori has not been elucidated. In this study, we performed agar dilution test and broth dilution test to determine MIC of kinetin against an H. pylori reference strain. In particular, we isolated H. pylori from gastric biopsies and confirmed inhibitory effect of kinetin against 60 clinical isolates of H. pylori. To elucidate the inhibitory mechanism of kinetin on H. pylori growth, we performed RT-PCR and found that kinetin down-regulated dnaA and holB expression both of which are ne...

Urinary tract infection (UTI) is one of the most common bacterial infections and is predominantly... more Urinary tract infection (UTI) is one of the most common bacterial infections and is predominantly caused by uropathogenic Escherichia coli (UPEC). UPEC strains generally possess several genes encoding virulent factors, which are mostly adhesins, toxins, bacteriocin and siderophores. E. coli is composed of four main phylogenetic group (A, B1, B2, D) and virulent extra-intestinal strains mainly belong to groups B2 and D. Prescription of ciprofloxacin, a kind of fluoroquinolone group antibiotics, is increasing now a days, but resistance to this drug is also increasing. A total of 188 strains of E. coli were collected. Thirteen strains were collected from healthy students in 2011 and 175 strains from patients with urinary tract infection in 2010. Virulence factor genes (papC, fimG/H, sfaD/E, hlyA, cnf1, and usp) were amplified by polymerase chain reaction (PCR) methods for phylogenetic group (A, B1, B2, D) detection. Ciprofloxacin susceptibility test was performed by disk diffusion meth...

Biomedical Science Letters, 2020

Ingestion of food contaminated with microorganism, if not always, could lead to severe health pro... more Ingestion of food contaminated with microorganism, if not always, could lead to severe health problem. Preservatives has been added to food to prevent food from being contaminated with microorganism. But, these have potential to threaten the health. Therefore, much effort has been taken to find the safe materials showing the anti-microbial activity. In this study, we investigated the anti-bacterial activity of Oenothera lamarckiana aerial part extract against eight bacteria strain. In paper disc assay, extract inhibited the growth of Staphylococcus aureus, Methicillin-resistant S. aureus, Bacillus cereus and Shigella dysenteriae at 200 μg/disc, but not against Escherichia coli, E. coli O157:H7, Salmonella Typhi and S. enteritidis. Minimum inhibitory concentration (MIC) against Staphylococcus aureus, Methicillin-resistant S. aureus, Bacillus cereus and Shigella dysenteriae is 250, 250, 500 and 500 μg/mL, respectively. Compared with reported MIC of other plant resources, O. lamarckiana aerial part extract showed the relatively high anti-bacterial activity. O. lamarckiana aerial part could be suitable for the preservative development. But, it still remains to be studied to evaluate safety and so on.

The Korean Journal of Gastroenterology, 2019

Background/Aims: Helicobacter pylori (H. pylori) infections, which cause a variety of gastrointes... more Background/Aims: Helicobacter pylori (H. pylori) infections, which cause a variety of gastrointestinal symptoms, are common in South Korea. Recent reports have shown a decline in the H. pylori eradication rates. β-caryophyllene is a natural bicyclic sesquiterpene that occurs in a wide range of plant species, such as cloves, basil, and cinnamon. β-caryophyllene has been reported to have anti-inflammatory and anti-bacterial effects. This study investigated the inhibitory effects of β-caryophyllene on H. pylori and its potential role as an alternative gastrointestinal drug. Methods: This 8-week, randomized double-blind, placebo-controlled trial categorized subjects into a β-caryophyllene group (33 patients who received 126 mg/day of β-caryophyllene) and a placebo group (33 patients who received a placebo preparation). The inflammation level of H. pylori infiltration and the eradication rates were evaluated endoscopically and with the urea breath test (UBT) in both groups before and after administering the medication. The serum cytokine levels (tumor necrosis factor-α, and interleukin [IL]-1β and IL-6) were compared in both groups before and after administering the medication. Results: Complete eradication was not observed in either group. Moreover, there was no significant change in the UBT and updated Sydney score. On the other hand, the β-caryophyllene group showed significant improvement in nausea (p=0.025) and epigastric pain (p=0.018), as well as a decrease in the serum IL-1β levels (p=0.038). Conclusions: β-caryophyllene improves dyspepsia symptoms and can be considered a useful supplementary treatment for gastrointestinal disease.

The Korean Journal of Clinical Laboratory Science, 2018

This study examined the effects of zerumbone on monocyte migration. Monocytes are recognized as i... more This study examined the effects of zerumbone on monocyte migration. Monocytes are recognized as important mediators of various inflammatory diseases, and the possibility of controlling inflammatory diseases by regulating the monocyte functions, such as activity and mobility, has been reported. MCP-1, which is a chemokine with levels that increase upon inflammation, causes the migration of the monocyte cell line, THP-1. Migration occurred at a concentration of 10 ng/mL MCP-1, and the highest migration occurred at 100 ng/mL and 200 ng/mL. MCP-1-induced THP-1 migration decreased by more than 40% in the presence of zerumbone. The concentration of cAMP, an important secondary messenger of the CCR2 signaling pathway, the MCP-1 receptor, was increased in the culture medium after a zerumbone treatment. The concentrations of cAMP decreased significantly under the MCP-1 treatment condition only. On the other hand, an increase in cAMP was observed when zerumbone and MCP-1 were treated simultaneously. Erk phosphorylation induced by an MCP-1 treatment was also found to decrease with the zerumbone treatment. This study introduces the possibility of controlling inflammatory diseases through the function of zerumbone, which regulates the migration of monocytes.

International Journal of Molecular Sciences, 2019

H. pylori is classified as a group I carcinogen by WHO because of its involvement in gastric canc... more H. pylori is classified as a group I carcinogen by WHO because of its involvement in gastric cancer development. Several reports have suggested anti-bacterial effects of menadione, although the effect of menadione on major virulence factors of H. pylori and H. pylori-induced inflammation is yet to be elucidated. In this study, therefore, we demonstrated that menadione has anti-H. pylori and anti-inflammatory effects. Menadione inhibited growth of H. pylori reference strains and clinical isolates. Menadione reduced expression of vacA in H. pylori, and translocation of VacA protein into AGS (gastric adenocarcinoma cell) was also decreased by menadione treatment. This result was concordant with decreased apoptosis in AGS cells infected with H. pylori. Moreover, cytotoxin-associated protein A (CagA) translocation into H. pylori-infected AGS cells was also decreased by menadione. Menadione inhibited expression of several type IV secretion system (T4SS) components, including virB2, virB7,...

Bioscience, biotechnology, and biochemistry, Jan 5, 2018

Inflammation induced by Helicobacter pylori infection related to gastric carcinogenesis. In this ... more Inflammation induced by Helicobacter pylori infection related to gastric carcinogenesis. In this study, we have investigated the anti-inflammatory effect and its mechanism of kaempferol in the inflammatory response caused by H. pylori infection in vitro. We found that kaempferol reduced the expression of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-8) and production of IL-8 in AGS cells. In addition, kaempferol suppressed translocation of cytotoxin-associated gene A (CagA) and vacuolating cytotoxin A (VacA) of H. pylori to AGS cells. It was due to decreased transcription of type IV secretion system (T4SS) components involved in CagA injection and secretion system subunit protein A (SecA) of type V secretion system (T5SS) involved in VacA secretion by kaempferol. In conclusion, kaempferol shows the anti-inflammatory effect by suppressing the translocation of CagA and VacA proteins and leading to the down-regulation of pro-inflammatory cytokines. CagA: cytotoxin-associated gene A;...

Molecular nutrition & food research, Feb 16, 2017

Black rice extract (BRE) contains cyanidin 3-O-glucoside (C3G), an anthocyanin, as the major comp... more Black rice extract (BRE) contains cyanidin 3-O-glucoside (C3G), an anthocyanin, as the major component. In this study, we found that BRE inhibited the mRNA and protein expression of genes encoding cytotoxin-associated protein A (cagA) and vacuolating protein A (vacA) in Helicobacter pylori 60190 strain. We performed RT-PCR and western blotting to show that BRE inhibited the mRNA and protein expression of SecA. Because SecA is involved in VacA export in bacteria, our result suggested a positive correlation between BRE-induced inhibition of secA expression and VacA secretion. Further, we performed MTT assay and flow cytometry to show that BRE decreased the apoptosis of H. pylori-infected KATO III cells. Finally, we performed western blotting to show that the cell-protective effect of BRE was associated with decreased levels of active proapoptotic proteins caspases and PARP and increased levels of antiapoptotic proteins survivin and XIAP in H. pylori-infected cells. Thus, our results i...