• Title/Summary/Keyword: exRNA

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Extracellular RNAs and Extracellular Vesicles: Inception, Current Explorations, and Future Applications

  • Perumal, Ayyappasamy Sudalaiyadum;Chelliah, Ramachandran;Datta, Saptashwa;Krishna, Jayachandran;Samuel, Melvin S.;Ethiraj, Selvarajan;Park, Chae Rin
    • Journal of Food Hygiene and Safety
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    • v.35 no.6
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    • pp.535-543
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    • 2020
  • In addition to the ubiquitous roles of cellular RNA in genetic regulations, gene expression and phenotypic variations in response to environmental cues and chemotactic signals, the regulatory roles of a new type of RNA called extracellular RNAs (exRNAs) are an up-and-coming area of research interest. exRNA is transported outside the cell through membrane blebs known as membrane vesicles or extracellular vesicles (EVs). EV formation is predominant and conserved among all microbial forms, including prokaryotes, eukaryotes, and archaea. This review will focus on the three major topics concerning bacterially derived exRNAs, i.e., 1) the discovery of exRNA and influence of extraneous RNA over bacterial gene regulations, 2) the known secretion mechanism for the release of exRNA, and 3) the possible applications that can be devised with these exRNA secreted by different gram-negative and gram-positive bacteria. Further, this review will also provide an opinion on exRNA- and EV-derived applications such as the species-specific exRNA markers for diagnostics and the possible roles of exRNA in probiotics and the epigenetic regulations of the gut microbiome.

Therapeutic applications of gene editing in chronic liver diseases: an update

  • Shin, Ji Hyun;Lee, Jinho;Jung, Yun Kyung;Kim, Kyeong Sik;Jeong, Jaemin;Choi, Dongho
    • BMB Reports
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    • v.55 no.6
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    • pp.251-258
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    • 2022
  • Innovative genome editing techniques developed in recent decades have revolutionized the biomedical research field. Liver is the most favored target organ for genome editing owing to its ability to regenerate. The regenerative capacity of the liver enables ex vivo gene editing in which the mutated gene in hepatocytes isolated from the animal model of genetic disease is repaired. The edited hepatocytes are injected back into the animal to mitigate the disease. Furthermore, the liver is considered as the easiest target organ for gene editing as it absorbs almost all foreign molecules. The mRNA vaccines, which have been developed to manage the COVID-19 pandemic, have provided a novel gene editing strategy using Cas mRNA. A single injection of gene editing components with Cas mRNA is reported to be efficient in the treatment of patients with genetic liver diseases. In this review, we first discuss previously reported gene editing tools and cases managed using them, as well as liver diseases caused by genetic mutations. Next, we summarize the recent successes of ex vivo and in vivo gene editing approaches in ameliorating liver diseases in animals and humans.

New report on cyanophyte in Korea, Microseira wollei (Farlow ex Gomont) G.B.McGregor and Sendall ex Kennis (Oscillatoriaceae)

  • Bae, Eun Hee;Kang, Jae-Shin;Park, Chong-Sung
    • Journal of Species Research
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    • v.9 no.3
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    • pp.210-217
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    • 2020
  • Microseira wollei (Farlow ex Gomont) G.B.McGregor and Sendall ex Kennis, a mat-forming filamentous harmful cyanobacterium, has historically been found in the United States. Microseira wollei produces neurotoxins and hepatotoxins which affect declining water quality. In the present research, we report of unrecorded M. wollei with morphology, TEM anatomy, molecular phylogeny on the Korean population. Based on 16S rRNA gene sequences, Korean population were different by 0.02% (2 bp) to the Japanese population, 1.2-1.3% to the Australian population, and 2.5-3.7% to the United States populations. nifH gene sequences were 8.4-8.7% different to Australian ones and 3.5-3.8% to other population, however molecular phylogenetic analysis of M. wollei living in Korea revealed monophyly with the geographical populations of U.S.A., Australia, and other geographical populations. Since the mat of M. wollei has been reported to be maintained for several years in other countries, it is necessary further investigate the seasonal and regional distribution of this species in Korea.

The inhibitory effect of swimming exercise on inflammation in adipose tissue of obese mice after ovariectomy (수영 운동이 난소절제 후 비만 쥐의 지방조직에서 염증에 미치는 억제 효과)

  • Jeong, Sun-Hyo
    • Journal of the Korean Applied Science and Technology
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    • v.37 no.5
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    • pp.1125-1137
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    • 2020
  • This study investigated whether swimming exercise suppresses(: inhibites) the inflammatory response in adipose tissue in obese mice induced by a high fat diet after ovariectomy in female mice. Experimental group and control group were divided into sham-opereated group (Sham), ovariectomized group (OVX), and ovariectomized group with swimming exercise (OVX/Ex). All female mice fed high fat diet (45% fat) for 8 weeks. Compared with the Sham, the OVX increased the weight of visceral adipose tissue including parametrial, retroperitoneal, and mesenteric adipose tissue. Compared to the OVX, the OVX/Ex demonstrated reductions the weight of visceral adipose tissue. Compared to the Sham, the OVX decreased the mRNA expression of IκBα and increased the mRNA expression of inflammatory cytokines (L-6, MCP-1, TNF-α and leptin) in adipose tissue. But the OVX/Ex appeared to increase the mRNA expression of IκBα and decrease the mRNA expression of inflammatory cytokines in adipose tissue, compared with the OVX. This findings suggested that swimming exercise is useful for preventing adipose tissue inflammation, which will be effective in the prevention and treatment of obesity in obese mice induced obesity by a high fat diet after ovariectomy.

Gynostemma pentaphyllum extract and its active component gypenoside L improve the exercise performance of treadmill-trained mice

  • Kim, Yoon Hee;Jung, Jae In;Jeon, Young Eun;Kim, So Mi;Hong, Su Hee;Kim, Tae Young;Kim, Eun Ji
    • Nutrition Research and Practice
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    • v.16 no.3
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    • pp.298-313
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    • 2022
  • BACKGROUND/OBJECTIVES: The effectiveness of natural compounds in improving athletic ability has attracted attention in both sports and research. Gynostemma pentaphyllum (Thunb.) leaves are used to make traditional herbal medicines in Asia. The active components of G. pentaphyllum, dammarane saponins, or gypenosides, possess a range of biological activities. On the other hand, the anti-fatigue effects from G. pentaphyllum extract (GPE) and its effective compound, gypenoside L (GL), remain to be determined. MATERIALS/METHODS: This study examined the effects of GPE on fatigue and exercise performance in ICR mice. GPE was administered orally to mice for 6 weeks, with or without treadmill training. The biochemical analysis in serum, glycogen content, mRNA, and protein expressions of the liver and muscle were analyzed. RESULTS: The ExGPE (exercise with 300 mg/kg body weight/day of GPE) mice decreased the fat mass percentage significantly compared to the ExC mice, while the ExGPE showed the greatest lean mass percentage compared to the ExC group. The administration of GPE improved the exercise endurance and capacity in treadmill-trained mice, increased glucose and triglycerides, and decreased the serum creatine kinase and lactate levels after intensive exercise. The muscle glycogen levels were higher in the ExGPE group than the ExC group. GPE increased the level of mitochondrial biogenesis by enhancing the phosphorylation of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) protein and the mRNA expression of nuclear respiratory factor 1, mitochondrial DNA, peroxisome proliferator-activated receptor-δ, superoxide dismutase 2, and by decreasing the lactate dehydrogenase B level in the soleus muscle (SOL). GPE also improved PGC-1α activation in the SOL significantly through AMPK/p38 phosphorylation. CONCLUSIONS: These results showed that GPE supplementation enhances exercise performance and has anti-fatigue activity. In addition, the underlying molecular mechanism was elucidated. Therefore, GPE is a promising candidate for developing functional foods and enhancing the exercise capacity and anti-fatigue activity.

Aqueous Extract of Schizandra chinensis Suppresses Dextran Sulfate Sodiuminduced Generation of IL-8 and ROS in the Colonic Epithelial Cell Line HT-29

  • Lee, Young-Mi;Lee, Kang-Soo;Kim, Dae-Ki
    • Natural Product Sciences
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    • v.15 no.4
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    • pp.185-191
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    • 2009
  • Intestinal epithelial cells (IEC) play an important role in the mucosal immune system. IEC-derived mediators of inflammatory cascades play a principal role in the development of colon inflammation. The aim of this study was to investigate the inhibitory effect of aqueous extracts of Schizandra chinensis fruits (SC-Ex) on the production of inflammatory mediators by the human colonic epithelial cells. HT-29 cells were stimulated with dextran sulfate sodium in the presence or absence of SC-Ex to examine the cytoprotection and production of IL-8 and reactive oxygen species (ROS). It was shown that dextran sulfate sodium (DSS) caused the reduction of cell viability and production of IL-8 and ROS in DSS-treated HT-29 cells. We observed that the treatment of SC-Ex protected significantly cell proliferation from DSS-induced damage in dose-dependent manner. SC-Ex (10 and 100 ${\mu}g$/ml) also suppressed DSS-induced production of IL-8 mRNA and protein. Moreover, DSS-induced ROS production was inhibited markedly by the treatment of 100 ${\mu}g$/ml SC-Ex. These results suggest that SC-Ex has the protective effects on DSS-induced cell damage and the release of inflammatory mediators in the intestinal epithelial cells.

Effect of exercise and diet intervention on endoplasmic reticulum (ER) stress in rat skeletal muscle and adipose tissue (운동부하가 고지방식이 유도 비만흰쥐의 골격근 및 지방조직의 ER (Endoplasmic Reticulum)스트레스에 미치는 영향)

  • Kim, Gi Chool;Park, Kyung Sil;Kim, Hyun Kook;Kim, Ki Hoon
    • Journal of Nutrition and Health
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    • v.45 no.5
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    • pp.420-428
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    • 2012
  • The purpose of this study is to investigate the effects of eight weeks high fat intake and regular exercise in skeletal muscle and adipose tissue for Endoplasmic Reticulum (ER) stress in rats. This experiment involved 32 subjects (sprague-dawley rats) divided into four groups as follows: chow group (Chow, n = 8), chow and exercise group (Chow + EX, n = 8), high fat diet-induced hyperlipidemia group (HF, n = 8), and HF and exercise group (HF + EX, n = 8). As a result, there were significant decrease in body weight and abdominal fat, and blood lipid level was significantly improved by exercise for eight weeks (p < .05). There were variables changed about the skeletal muscle and ER stress in GRP78, XBP-1, ATF4, CHOP and JNK mRNA. There increased in mRNA factor by exercise, especially GRP78, and ATF4 mRNA were significantly increased in exercise (p < .05). However, there were increased in adipose tissue by exercise and there were significantly decreased in mRNA factor by high fat diet (p < .05). Consequently, this study suggests that the consistent exercise was more improved of obesity factor, such as dyslipidemia, hyperlipidemia, hyperglycemia, as well as body weight or abdominal fat. The response of ER stress in adipose tissue and skeletal muscle were more sensitive in exercise than high fat diet feed.

Dual effects of a CpG-DNAzyme targeting mutant EGFR transcripts in lung cancer cells: TLR9 activation and EGFR downregulation

  • Jang, Dahye;Baek, Yu Mi;Park, Hanna;Hwang, Yeo Eun;Kim, Dong-Eun
    • BMB Reports
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    • v.51 no.1
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    • pp.27-32
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    • 2018
  • Non-small-cell lung cancer (NSCLC) is commonly caused by a mutation in the epidermal growth factor receptor (EGFR) and subsequent aberrant EGFR signaling with uncontrolled kinase activity. A deletion mutation in EGFR exon 19 is frequently observed in EGFR gene mutations. We designed a DNAzyme to suppress the expression of mutant EGFR by cleaving the mutant EGFR mRNA. The DNAzyme (named Ex19del Dz) specifically cleaved target RNA and decreased cancer cell viability when transfected into gefitinib-resistant lung cancer cells harboring EGFR exon 19 deletions. The DNAzyme decreased EGFR expression and inhibited its downstream signaling pathway. In addition to EGFR downregulation, Ex19del Dz containing CpG sites activated Toll-like receptor 9 (TLR9) and its downstream signaling pathway via p38 kinase, causing an immunostimulatory effect on EGFR-mutated NSCLC cells. Thus, dual effects of this DNAzyme harboring the CpG site, such as TLR9 activation and EGFR downregulation, leads to apoptosis of EGFR-mutated NSCLC cells.

Change of Mitochondrial Biogenesis Genes on Regular Exercise Training in Adipocytes of Ovariectomized Rats Fed on High Fat Diet (규칙적 운동이 고지방식이 난소절제흰쥐의 지방세포에서 미토콘드리아 생합성 유전자들의 변화)

  • Lee, Jin
    • Journal of Life Science
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    • v.21 no.7
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    • pp.997-1003
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    • 2011
  • Menopause and obesity are associated with metabolism. The purpose of this study was to examine the changes of PPAR${\gamma}$, PGC-1(${\alpha},\;{\beta}$), NRf-1 and TFAM mRNA and mitochondria biogenesis in adipocytes and investigate the effect of swimming exercise for 6weeks on ovariectomized rats. Rats were randomly assigned to 3 groups: (1) ovariectomized rats fed with a control diet (C, n=4), (2) ovariectomized rats fed with high fat diet (H, n=4), and (3) ovariectomized rats trained to exercise and fed with high fat diet (H+EX, n=4). Exercise was performed by swimming for 5 days/wk, with a progressive increase in exercise over the course of 6 weeks. Results showed that the fat tissue weight in the H group was markedly increased (p<0.01) compared to other groups, however, regular exercise significantly decreased fat weight. The PPAR-${\gamma}$ (p<0.05), PGC-$1{\alpha}$ (p<0.01), -$1{\beta}$ (p<0.05), NRf-1 (p<0.01) and TFAM (p<0.05) mRNA expression in the adipocytes of H+EX were higher than in the H group. These results suggest that regular exercise for 6 weeks might exert positive effects by increasing PPAR-${\gamma}$, PGC-1 (${\alpha},\;{\beta}$), NRf-1 and TFAM mRNA expression and mitochondria in adipocytes. Thus, regular exercise may be helpful in the improvement of mitochondria biogenesis function in obese, ovariectomized rats.

Expression of Ajuba, a Novel LIM Protein, is Regulated by Endorlasmic Reticulum Stress (소포체 스트레스가 Ajuba 발현유도)

  • Park, Sang-Mi;Kwon, Ki-Sang;Yun, Eun-Young;Goo, Tae-Won;Kwon, O-Yu
    • Journal of Life Science
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    • v.17 no.7 s.87
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    • pp.1023-1025
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    • 2007
  • Ajuba is a number of proteins containing cytosolic LIM domain. Its function may provide a new pathway whereby cell-cell adhesive events are transmitted to the nucleus to regulate cell proliferation and differentiation decisions. Here, Ajuba gene expression was investigated its molecular properties associated with endoplasmic reticulum (ER) stresses (tunicamycin, DTT, A23187 and BFA) which induced remarkable ex-pression of Ajuba mRNA. The mRNA half life of Ajuba was also determined, its half life of Ajuba mRNA in FRTL-5 cells was approximately 2 hr after the initial translation. Although the obvious bioligical function of Ajuba is not clear, on the base of the results, Ajuba gene expression is deeply associated with ER stresses.