• Molecules and Cells
• /
• v.42 no.6
• /
• pp.448-459
• /
• 2019

The phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway is a promising target for gastric cancer (GC) treatment; however the efficacy of PI3K/mTOR dual inhibitors in GC has not yet been maximized. Additionally, the effect of autophagy regulation by PI3K/mTOR dual inhibitors has not been clearly elucidated in GC treatment. We aimed to show that our newly developed PI3K/mTOR dual inhibitor, CMG002, when combined with an autophagy inhibitor, chloroquine (CQ), potently induces effective cancer cell death in Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC) cells, where both the PI3K/AKT/mTOR and autophagy pathways play important roles in disease pathogenesis. EBV- and mock-infected AGS and NUGC3 GC cell lines were treated with CMG002 +/- CQ. PI3K/AKT/mTOR signaling pathway mediators, cellular apoptosis and autophagy markers were confirmed by Western blot assay. Cell viability was assessed using the Cell Counting Kit-8 (CCK-8) assay. CMG002 effectively blocked the PI3K/AKT/mTOR pathway by markedly decreasing phosphorylation of AKT and its downstream mediator S6. CMG002 induced G0/G1 cell cycle arrest and enhanced apoptotic cell death in AGS and NUGC3 cells, particularly EBV-infected cells compared with mock-infected cells, as confirmed by flow cytometric analyses and TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assays. The combination of CMG002 plus CQ synergistically increased apoptotic cell death in EBV-infected GC cell lines when compared with CMG002 alone (P < 0.05). Our results suggest that the new PI3K/mTOR dual inhibitor, CMG002, when used in combination with the autophagy inhibitor, CQ, provides enhanced therapeutic efficacy against EBVaGC.

• Journal of Life Science
• /
• v.31 no.1
• /
• pp.28-36
• /
• 2021

Edwardsiella piscicida is a significant cause of hemorrhagic septicemia in fish and gastrointestinal infections in humans. Survival bacteria require specialized mechanisms to adapt to environmental fluctuations. Hence, to understand the mechanism through which E. piscicida senses and responds to environmental osmolarity changes, we determined the protein expression profile and physiological properties under various salinity conditions in this study. The OmpR protein is a part of the Env-ZOmpR two-component system that has been implicated in sensing salt stress in bacteria. However, the physiological role played by this protein in E. piscicida remains to be elucidated. Therefore, in this work, the function of the OmpR protein in response to salt stress was investigated. Phenotypic analysis revealed that, in the mutant, three of the biochemical phenotypes were different from the wild type, including, citrate utilization, hydrogen sulfide, and indole production. Introduction of the plasmid containing the entire ompR gene to the mutant strain returned it to its parental phenotype. The retarded growth rate also partially recovered. Furthermore, in our studies, OmpR was not found to be related to cell motility. Taken together, our results from the mutational analysis, the growth assay, MALDI-TOF MS, qRT-PCR, and the phenotype studies suggest that the OmpR of E. piscicida is implicated in osmoregulation, growth, expression of porins (ETAE_1826), virulence-related genes (EseC, EseD and EvpC), and certain genes of unknown function (ETAE_1540 and ETAE_2706).

• Journal of Microbiology and Biotechnology
• /
• v.30 no.12
• /
• pp.1819-1826
• /
• 2020

Increasing evidence suggests a potential role of microbial colonization in the inception of chronic airway diseases. However, it is not clear whether the lung and gut microbiome dysbiosis is coincidental or a result of mutual interaction. In this study, we investigated the airway microbiome in interleukin 13 (IL-13)-rich lung environment and related alterations of the gut microbiome. IL-13-overexpressing transgenic (TG) mice presented enhanced eosinophilic inflammatory responses and mucus production, together with airway hyperresponsiveness and subepithelial fibrosis. While bronchoalveolar lavage fluid and cecum samples obtained from 10-week-old IL-13 TG mice and their C57BL/6 wild-type (WT) littermates showed no significant differences in alpha diversity of lung and gut microbiome, they presented altered beta diversity in both lung and gut microbiota in the IL-13 TG mice compared to the WT mice. Lung-specific IL-13 overexpression also altered the composition of the gut as well as the lung microbiome. In particular, IL-13 TG mice showed an increased proportion of Proteobacteria and Cyanobacteria and a decreased amount of Bacteroidetes in the lungs, and depletion of Firmicutes and Proteobacteria in the gut. The patterns of polymicrobial interaction within the lung microbiota were different between WT and IL-13 TG mice. For instance, in IL-13 TG mice, lung Mesorhizobium significantly affected the alpha diversity of both lung and gut microbiomes. In summary, chronic asthma-like pathologic changes can alter the lung microbiota and affect the gut microbiome. These findings suggest that the lung-gut microbial axis might actually work in asthma.

• Journal of Gastric Cancer
• /
• v.21 no.2
• /
• pp.142-154
• /
• 2021

Purpose: Screening image-enhanced endoscopy for gastrointestinal malignant lesions has progressed. However, the influence of the color enhancement settings for the laser endoscopic system on the visibility of lesions with higher color contrast than their surrounding mucosa has not been established. Materials and Methods: Forty early gastric cancers were retrospectively evaluated using color enhancement settings C1 and C2 for laser endoscopic systems with blue laser imaging (BLI), BLI-bright, and linked color imaging (LCI). The visibilities of the malignant lesions in the stomach with the C1 and C2 color enhancements were scored by expert and non-expert endoscopists and compared, and the color differences between the malignant lesions and the surrounding mucosa were assessed. Results: Early gastric cancers mainly appeared orange-red on LCI and brown on BLI-bright or BLI. The surrounding mucosae were purple on LCI regardless of the color enhancement but brown or pale green with C1 enhancement and dark green with C2 enhancement on BLI-bright or BLI. The mean visibility scores for BLI-bright, BLI, and LCI with C2 enhancement were significantly higher than those with C1 enhancement. The superiority of the C2 enhancement was not demonstrated in the assessments by non-experts, but it was significant for experts using all modes. The C2 color enhancement produced a significantly greater color difference between the malignant lesions and the surrounding mucosa, especially with the use of BLI-bright (P=0.033) and BLI (P<0.001). C2 enhancement tended to be superior regardless of the morphological type, Helicobacter pylori status, or the extension of intestinal metaplasia around the cancer. Conclusions: Appropriate color enhancement settings improve the visibility of malignant lesions in the stomach and color contrast between the malignant lesions and the surrounding mucosa.

• Journal of Korean Society of Health-System Pharmacists
• /
• v.35 no.4
• /
• pp.453-462
• /
• 2018

Background : The prevalence of chronic hepatitis C virus (HCV) tends to be higher in the elderly. Pegylated interferon and ribavirin therapy (Peg-IFN/RBV) was recommended as the first-line treatment in the past decades, but this regimen showed unsatisfactory results in terms of safety and efficacy especially in elderly patients. Recently, it was demonstrated that dual therapy with daclatasvir and asunaprevir was well tolerated and led to high sustained virological response (SVR) rates, irrespective of age. We conducted a study to evaluate the efficacy and safety of daclatasvir plus asunaprevir by involving elderly patients aged above 65 years. Methods : We retrospectively analyzed clinical data from chronic hepatitis C virus (HCV) genotype 1b patients treated with daclatasvir plus asunaprevir from September 2015 to December 2016 at Seoul St. Mary's hospital. The patients were divided into two groups as elderly patients (older than 65 years) and non-elderly patients (younger than 65 years) and compared the efficacy and safety. Results : A total of 112 patients were treated with daclatasvir plus asunaprevir for chronic hepatitis C. Among them, 101 patients completed the whole treatment, and in 88 patients the amount of HCV RNA was measured after 12 weeks of treatment. There was no significant difference in SVR at 12 weeks between both the groups (p=0.68). Typically, 91.4%(32/35) of elderly patients and 94.3%(50/53) of non-elderly patients achieved SVR12. Common adverse events included elevation in transaminase level, headache, and gastrointestinal disorders. There was no statistical difference in the symptoms between the two groups. Conclusions : The combination therapy with daclatasvir plus asunaprevir exhibited similar rates of SVR12 in HCV elderly patients without leading to further adverse events compared to non-elderly patients. Therefore, it is proposed that daclatasvir plus asunaprevir therapy could be considered as an effective and safe treatment, even in patients aged over 65 years.

• Food Science and Industry
• /
• v.54 no.1
• /
• pp.11-28
• /
• 2021

Air pollution caused by particulate matters (PM) has become a global issue. PM is known to threaten human health by causing respiratory and cardiovascular disease. PM can be introduced to human gastrointestinal track through food intake, causing inflammation and changes in gut microbiota. Even at low PM concentrations, prolonged exposure to PM can cause significant accumulation of PM in food products. The adsorption of PM onto food surfaces is expected to be strongly influenced by the properties of food surfaces, but few studies have been reported. This paper examines several important food surface properties that may affect the interactions between PM and food surfaces, including surface wettability, surface charge, and surface microstructure. Understanding the adsorption of PM onto food surfaces can provide useful guidance for classifying PM-sensitive foods and controlling food chains, including cultivation, processing, preservation, and cooking, to ensure food safety against PM.

• Journal of Dairy Science and Biotechnology
• /
• v.39 no.1
• /
• pp.27-35
• /
• 2021

The aim of this research was to investigate the potential application of casein phospho-peptide (CPP)/chitosan oligosaccharide (CSO) nanocomplexes to dairy foods. The physical stability of CPP/CSO nanocomplexes during storage in model dairy foods including milk and yogurt was assessed by measuring the size and polydispersity index of the nanocomplexes. Encapsulation efficiency and in vitro vitamin D release from CPP/CSO nanocomplexes during gastrointestinal digestion were determined using HPLC. CPP/CSO nanocomplexes with increased CPP concentrations and decreased pH displayed significantly increased average particle size. During storage in model dairy foods, CPP/CSO nanocomplexes prepared with lower CPP concentrations and raised pH exhibited excellent physical stability. Vitamin D encapsulation efficiency increased significantly (p<0.05) as CPP concentration and/or pH decreased. Less than 3% vitamin D were released under gastric digestion conditions in vitro, while 91% of encapsulated vitamin D was released by 2 h of incubation under intestinal conditions, indicating that CPP/CSO nanocomplexes could effectively protect vitamin D from gastric conditions for delivery to the intestines. In conclusion, CPP/CSO nanocomplexes can be applied to dairy foods as an effective vitamin D delivery system.

• Journal of Applied Biological Chemistry
• /
• v.64 no.1
• /
• pp.75-81
• /
• 2021

Recent gut microbiota studies have revealed the important roles of gut microbiota for our health. Increasing numbers of health functional foods have been developed every year. Development of functional food often includes ex- and in-vivo experiment to verify the beneficial effects of the functional food. To investigate effects of functional food on gut microbiota, animal models were often conducted. Beneficial effects of food can be evaluated based on how gut microbiota was shifted by food, which results in either increase in beneficial bacteria, decrease in potentially pathogenic bacteria or both. As animal experiments are generally time-consuming and laborious, we investigate how well in-vitro investigation of fecal microbiota may reflect dietary health benefits. Here, we tested 15 kinds of diets using two human subjects' fecal materials. Our results showed varying gut microbiota shifts according to diets, which suggested generally known beneficial diets (i.e. Kimchi, Chunggukjang) increased Lactobacillus and Bifidobacterium. Therefore, we suggest that in vitro fecal microbiota analysis could be used to evaluate beneficial effects of diets. Moreover, this method may be ideal to establish personalized diet.

• Journal of Life Science
• /
• v.32 no.3
• /
• pp.263-269
• /
• 2022

Cancer cachexia-anorexia is a multi-organ metabolic syndrome characterized by anorexia and weight loss. Generally, such symptoms are a serious problem in cancer patients, adversely affecting chemotherapy success and survival rate. Cachexia has been reported to accompany up to 80% of gastrointestinal cancers, such as pancreatic, lung, and colon cancer, though it is relatively rare in lymphoma or breast cancer patients. It is also known that cancer-induced anorexia occurs independently of chemotherapy, although decreased appetite due to chemotherapy is well reported. In terms of pathoflammatory cytokines that are excessively increased by tumor tissues. Since the mechanism of cancer cachexia is not yet fully understood, there are currently no therapeutic agents or diagnostic markers to treat it. A recently published study identified a substance secreted from cancer cells that induces cancer anorexia, and the molecular mechanism causing the eating disorder was discovered. An increase in the expression of this substance has been shown to be statistically correlated with the symptoms of cachexia in cancer patients, and it is therefore expected to be applicable in the diagnosis and development of therapeutic agents for cancer cachexia. This review article aims to provide an overview of the key molecular mechanisms of the anorexia and tissue wasting caused by cancer cachexia.

• Journal of the Korea Convergence Society
• /
• v.13 no.4
• /
• pp.573-582
• /
• 2022

In order to develop samultang with reduced side effects, modified samultang using omija was oral administered to rats with ovarian resection, and changes in evaluation indicators of functional efficacy in women's menopause were measured. In weight gain, relative weight of uterus and vagina, blood lipid-related indicators, and changes in blood estradiol, there was no statistically significant improvement effect in modified Samultang compared to the control group. However, the expression of estrogen receptor alpha and beta in intrauterine tissue tended to increase, and the expression of phosphorylated ERK, which is known to be involved in estrogen receptor signaling, showed a significant increase in activation in ERK and AKT. The expression amount of phosphorylation AKT was not significant, but showed an increasing tendency. Even though the test substance was administered in a relatively small dose, it is judged that the test substance modified Samultang has the ability to activate estrogen receptor. In the future, it is expected that it can be used as a useful natural mixture to show the efficacy of samultang with fewer gastrointestinal disorders.