The RNA-binding protein tristetraprolin (TTP) binds to adenosine-uridine AU-rich elements in the 3'-untranslated region of messenger RNAs and facilitates rapid degradation of the target mRNAs. Therefore, it regulates the expression of multiple cancer and immunity-associated transcripts. Furthermore, a lack of TTP in cancer cells influences cancer progression and predicts poor survival. Although the functions of TTP on cancer cells have previously been researched, the mechanism of TTP on the interaction between cancer cells with their micro-environment remains undiscovered. In this study, we admed to determine the role of cancer cell TTP during the interaction between tumor and immune cells, specifically regulatory T cells (Tregs). We evaluate the capability of TTP to modulate the antitumor immunity of GC and explored the underlying mechanism. The overexpression of TTP in GC cells dramatically increased peripheral blood mononuclear lymphocyte (PBML) -mediated cytotoxicity against GC cells. Increased cytotoxicity against TTP-overexpressed GC cells by PBMLs was determined by Treg development and infiltration. Surprisingly, we found the stabilization of programmed death-ligand 1 (PD-L1) mRNA was declining while TTP was elevated. The PD-L1 protein level was reduced in TTP-abundant GC cells. PD-L1 gas been found to play a pivotal role in Treg development and functional maintenance in immune system. Taken together, our results suggest the overexpression of TTP in GC cells not only affects cell survival and apoptosis but also increases PBMLs -mediated cytotoxicity against GC cells to decelerate tumor progression. Moreover, we identified PD-L1 as a critical TTP-regulated factor that contributes to inhibiting antitumor immunity.
Kim Ki-Yeon;Kim Hee-Gyu;Song Byeong-Chul;Cha Chang-Jun
Korean Journal of Microbiology
/
v.42
no.2
/
pp.160-163
/
2006
Brown rice contains rice bran and germ with higher nutritional value and dietary fiber content compared with the polished rice. However, brown rice has a limitation of poor digestion. fermented brown rice could be better nutritional source and improve digestibility. Therefore, we tried to select good fermentative microorganisms which have nutritional values with high amylase and protease activities, and probiotic effects. Nineteen micro-organisms, including eight Bacillus strains isolated from Chongkukjang and 11 lactic acid bacteria, were screened for the fermentation ability and enzyme production. The liquid broths containing 2.5%(w/v) of raw brown rice powder as a sole nutritional source were used for culture media. Among the strains tested, all of the Bacillus strains and two lactic acid bacteria (Leuconostoc gelidum and Pediococcus pentosaceus) showed increase in cell population and enzyme activities. The viable cell counts of all the Bacillus strains and two lactic acid bacteria exceeded $10^7 CFU/mL$. The maximal enzyme activities produced by Bacillus sp. Bl, Bacillus sp. B2, Bacillus sp. B11, L. gelidum and P. pentosaceus were 17.85, 17.50, 17.10, 17.10 and 3.24 U/mL for amylase and 22.48, 22.04, 23.76, 12.13, and 3.4 U/mL for pretense, respectively. Therefore, the results of this study demonstrated that the above strains could be potential starters for the fermentation of raw brown rice.
MicroRNAs (miRNAs) have been reported to be involved in many neurodegenerative diseases. The present study focused on the role of hsa-miR-144-3p in one of the neuro-degenerative diseases, Parkinson's disease (PD). Our study showed a remarkable down-regulation of miR-144-3p expression in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-treated SH-SY5Y cells. MiR-144-3p was then overexpressed and silenced in human SH-SY5Y cells by miRNA-mimics and miRNA-inhibitor transfections, respectively. Furthermore, ${\beta}$-amyloid precursor protein (APP) was identified as a target gene of miR-144-3p via a luciferase reporter assay. We found that miR-144-3p overexpression significantly inhibited the protein expression of APP. Since mitochondrial dysfunction has been shown to be one of the major pathological events in PD, we also focused on the role of miR-144-3p and APP in regulating mitochondrial functions. Our study demonstrated that up-regulation of miR-144-3p increased expression of the key genes involved in maintaining mitochondrial function, including peroxisome proliferator-activated receptor ${\gamma}$ coactivator-$1{\alpha}$(PGC-$1{\alpha}$), nuclear respiratory factor 1 (NRF-1) and mitochondrial transcription factor A (TFAM). Moreover, there was also a significant increase in cellular ATP, cell viability and the relative copy number of mtDNA in the presence of miR-144-3p overexpression. In contrast, miR-144-3p silencing showed opposite effects. We also found that APP overexpression significantly decreased ATP level, cell viability, the relative copy number of mtDNA and the expression of these three genes, which reversed the effects of miR-144-3p overexpression. Taken together, these results show that miR-144-3p plays an important role in maintaining mitochondrial function, and its target gene APP is also involved in this process.
T cells induce immune responses and thereby eliminate infected micro-organisms when peptides from the microbial proteins are bound to HLAs in the host cell surfaces, It is known that the more stable the binding of peptide to HLA is, the stronger the T cell response gets to remove more effectively the source of infection. Accordingly, if peptides (HLA binder) which can be bound stably to a certain HLA are found, those peptieds are utilized to the development of peptide vaccine to prevent infectious diseases or even to cancer. However, HLA is highly polymorphic so that HLA has a large number of alleles with some frequencies even in one population. Therefore, it is very inefficient to find the peptides stably bound to a number of HLAs by testing random possible peptides for all the various alleles frequent in the population. In order to solve this problem, computational methods have recently been developed to predict peptides which are stably bound to a certain HLA. These methods could markedly decrease the number of candidate peptides to be examined by biological experiments. Accordingly, this paper not only introduces a method of machine learning to predict peptides binding to an HLA, but also suggests a new prediction model so called 'knowledge-based genetic algorithm' that has never been tried for HLA binding peptide prediction. Although based on genetic algorithm (GA). it showed more enhanced performance than GA by incorporating expert knowledge in the process of the algorithm. Furthermore, it could extract rules predicting the binding peptide of the HLA alleles common in Koreans.
Exosomes are a type of extracellular vesicle containing proteins and messenger and microRNAs; they are secreted by all cell types. Once released, exosomes are selectively taken up by other cells adjacent or at a distance, releasing their contents and reprogramming the target cells. Since exosomes are natural vesicles produced by cells as small sizes, it is generally accepted that exosomes have a non-toxic nature and non-immunogenic behaviors. Recently, exosomes have elicited scientific attention as drug delivery vehicles to the central nervous system. The central nervous system has a blood-brain barrier that makes it difficult for drugs to penetrate. Thus, the blood-brain barrier has been a major obstacle to the development of drugs for treating neurodegenerative diseases. However, accumulating evidence suggests that exosomes can cross the blood-brain barrier primarily through transcytosis. Consequently, exosomes are expected to become a new delivery vehicle that can cross the blood-brain barrier and deliver drugs into the brain parenchyma. In addition, since different types of exosomes are secreted depending on the cell type and disease state, exosomes can also be utilized as biomarkers for the diagnosis of diseases in the central nervous system. In this review, we summarized recent research trends on exosomes, including clinical trials as biomarkers and treatment options for diseases in the central nervous system.
Wei Qin;Lin Yang;Xiaotong Chen;Shanyu Ye;Aijun Liu;Dongfeng Chen;Kunhua Hu
International Journal of Stem Cells
/
v.16
no.3
/
pp.326-341
/
2023
Background and Objectives: Osteoarthritis (OA) is a degenerative disease that leads to the progressive destruction of articular cartilage. Current clinical therapeutic strategies are moderately effective at relieving OA-associated pain but cannot induce chondrocyte differentiation or achieve cartilage regeneration. We investigated the ability of wedelolactone, a biologically active natural product that occurs in Eclipta alba (false daisy), to promote chondrogenic differentiation. Methods and Results: Real-time reverse transcription-polymerase chain reaction, immunohistochemical staining, and immunofluorescence staining assays were used to evaluate the effects of wedelolactone on the chondrogenic differentiation of mesenchymal stem cells (MSCs). RNA sequencing, microRNA (miRNA) sequencing, and isobaric tags for relative and absolute quantitation analyses were performed to explore the mechanism by which wedelolactone promotes the chondrogenic differentiation of MSCs. We found that wedelolactone facilitates the chondrogenic differentiation of human induced pluripotent stem cell-derived MSCs and rat bone-marrow MSCs. Moreover, the forkhead box O (FOXO) signaling pathway was upregulated by wedelolactone during chondrogenic differentiation, and a FOXO1 inhibitor attenuated the effect of wedelolactone on chondrocyte differentiation. We determined that wedelolactone reduces enhancer of zeste homolog 2 (EZH2)-mediated histone H3 lysine 27 trimethylation of the promoter region of FOXO1 to upregulate its transcription. Additionally, we found that wedelolactone represses miR-1271-5p expression, and that miR-1271-5p post-transcriptionally suppresses the expression of FOXO1 that is dependent on the binding of miR-1271-5p to the FOXO1 3'-untranscribed region. Conclusions: These results indicate that wedelolactone suppresses the activity of EZH2 to facilitate the chondrogenic differentiation of MSCs by activating the FOXO1 signaling pathway. Wedelolactone may therefore improve cartilage regeneration in diseases characterized by inflammatory tissue destruction, such as OA.
Laboratory experiments for the reaction with supercritical $CO_2$ under the $CO_2$ sequestration condition were performed to investigate the mineralogical and geochemical weathering process of the sandstones and mudstones in the Pohang basin. To simulate the supercritical $CO_2$-rock-groundwater reaction, rock samples used in the experiment were pulverized and the high pressurized cell (200 ml of capacity) was filled with 100 ml of groundwater and 30 g of powdered rock samples. The void space of the high pressurized cell was saturated with the supercritical $CO_2$ and maintained at 100 bar and $50^{\circ}C$ for 60 days. The changes of mineralogical and geochemical properties of rocks were measured by using XRD (X-Ray Diffractometer) and BET (Brunauer-Emmett-Teller). Concentrations of dissolved cations in groundwater were also measured for 60 days of the supercritical $CO_2$-rock-groundwater reaction. Results of XRD analyses indicated that the proportion of plagioclase and K-feldspar in the sandstone decreased and the proportion of illite, pyrite and smectite increased during the reaction. In the case of mudstone, the proportion of illite and kaolinite and cabonate-fluorapatite increased during the reaction. Concentration of $Ca^{2+}$ and $Na^+$ dissolved in groundwater increased during the reaction, suggesting that calcite and feldspars of the sandstone and mudstone would be significantly dissolved when it contacts with supercritical $CO_2$ and groundwater at $CO_2$ sequestration sites in Pohang basin. The average specific surface area of sandstone and mudstone using BET analysis increased from $27.3m^2/g$ and $19.6m^2/g$ to $28.6m^2/g$ and $26.6m^2/g$, respectively, and the average size of micro scale void spaces for the sandstone and mudstone decreased over 60 days reaction, resulting in the increase of micro pore spaces of rocks by the dissolution. Results suggested that the injection of supercritical $CO_2$ in Pohang basin would affect the physical property change of rocks and also $CO_2$ storage capacity in Pohang basin.
Kim, A-Ram;Youn, Seok-Hyun;Chung, Mi-Hee;Yoon, Sang-Chol;Moon, Chang-Ho
The Sea:JOURNAL OF THE KOREAN SOCIETY OF OCEANOGRAPHY
/
v.19
no.4
/
pp.287-301
/
2014
In order to understand environment condition and phytoplankton community before and after coastal upwelling, the influences of upwelling events on phytoplankton community were studied at 18 stations located the Southern part of East Sea, Korea from May to August 2013. The surface water masses showed low temperature and high salinity due to upwelling events at coastal stations (A1, B1, C1). Correlation between temperature and nutrients (DIP, r=-0.218, p<0.01; DIN, r=-0.306, p<0.01; silicate, r=-0.274, p<0.01) was significantly negative. This result could be explained that nutrients were supplied to surface water by the upwelling of bottom water. Phytoplankton communities were composed of 186 species. Phytoplankton abundance were relatively high in May (C1, $726{\times}10^3cells\;L^{-1}$) and July (A1, $539{\times}10^3cells\;L^{-1}$). Total chlorophyll a and micro-size fraction ($>20{\mu}m$) increased at coastal stations in July and August, while phytoplankton abundance and total chl. a was much low in June. Dominant species in June was Pseudo-nitzschia spp. of which the cell size was $309{\mu}m^3$. Cell size of Pseudo-nitzschia spp. was smaller than dominant species in other period. Therefore, the increase in total chloro-phyll a and the size of phytoplankton was resulted in the sufficient supply of nutrients. In contrast, these tendencies were not observed at outside stations. These results suggested that coastal upwelling was an important influencing factor to determine the species composition and standing stock of phytoplankton community in the coastal waters of the Southern part of East Sea, Korea.
Korean Journal of Air-Conditioning and Refrigeration Engineering
/
v.21
no.12
/
pp.715-732
/
2009
This article reviews the papers published in the Korean Journal of Air-Conditioning and Refrigeration Engineering during 2008. It is intended to understand the status of current research in the areas of heating, cooling, ventilation, sanitation, and indoor environments of buildings and plant facilities. Conclusions are as follows. (1) Research trends in thermal and fluid engineering have been surveyed in the categories of general fluid flow, fluid machinery and piping, new and renewable energy, and fire. Well-developed CFD technologies were widely applied in developing facilities and their systems. New research topics include fire, fuel cell, and solar energy. Research was mainly focused on flow distribution and optimization in the fields of fluid machinery and piping. Topics related to the development of fans and compressors had been popular, but were no longer investigated widely. Research papers on micro heat exchangers using nanofluids and micro pumps were also not presented during this period. There were some studies on thermal reliability and performance in the fields of new and renewable energy. Numerical simulations of smoke ventilation and the spread of fire were the main topics in the field of fire. (2) Research works on heat transfer presented in 2008 have been reviewed in the categories of heat transfer characteristics, industrial heat exchangers, and ground heat exchangers. Research on heat transfer characteristics included thermal transport in cryogenic vessels, dish solar collectors, radiative thermal reflectors, variable conductance heat pipes, and flow condensation and evaporation of refrigerants. In the area of industrial heat exchangers, examined are research on micro-channel plate heat exchangers, liquid cooled cold plates, fin-tube heat exchangers, and frost behavior of heat exchanger fins. Measurements on ground thermal conductivity and on the thermal diffusion characteristics of ground heat exchangers were reported. (3) In the field of refrigeration, many studies were presented on simultaneous heating and cooling heat pump systems. Switching between various operation modes and optimizing the refrigerant charge were considered in this research. Studies of heat pump systems using unutilized energy sources such as sewage water and river water were reported. Evaporative cooling was studied both theoretically and experimentally as a potential alternative to the conventional methods. (4) Research papers on building facilities have been reviewed and divided into studies on heat and cold sources, air conditioning and air cleaning, ventilation, automatic control of heat sources with piping systems, and sound reduction in hydraulic turbine dynamo rooms. In particular, considered were efficient and effective uses of energy resulting in reduced environmental pollution and operating costs. (5) In the field of building environments, many studies focused on health and comfort. Ventilation. system performance was considered to be important in improving indoor air conditions. Due to high oil prices, various tests were planned to examine building energy consumption and to cut life cycle costs.
Park, Jin-Woo;Lee, Deog-Hye;Yeo, Shin-Il;Park, Kwang-Bum;Choi, Seok-Kyu;Suh, Jo-Young
Journal of Periodontal and Implant Science
/
v.37
no.sup2
/
pp.427-445
/
2007
To improve osseointegration at the boneto-implant interface, several studies have been carried out to modify titanium surface. Variations in surface texture or microtopography may affect the cellular response to an implant. Osteoblast-like cells attach more readily to a rougher titanium surface, and synthesis of extracellular matrix and subsequent mineralization were found to be enhanced on rough or porous coated titanium. However, regarding the effect of roughened surface by physical and mechanical methods, most studies carried out on the reactions of cells to micrometric topography, little work has been performed on the reaction of cells to nanotopography. The purpose of this study was to examme the response of osteoblast-like cell cultured on blasted surfaces and alkali treated surfaces, and to evaluate the influence of surface texture or submicro-scaled surface topography on the cell attachment, cell proliferation and the gene expression of osteoblastic phenotype using ROS 17/2.8 cell lines. In scanning electron micrographs, the blasted, alkali treated and machined surfaces demonstrated microscopic differences in the surface topography. The specimens of alkali treatment had a submicro-scaled porous sur-face with pore size about 200 nm. The blasted surfaces showed irregularities in morphology with small(<10 ${\mu}m$) depression and indentation among flatter-appearing areas of various sizes. Based on profilometry, the blasted surfaces was significantly rougher than the machined and the alkali treated surfaces (p$TiO_2$) were observed on alkali treated surfaces, whereas not observed on machined and blasted surfaces. The attachment morphology of cells according to time was observed by the scanning electron microscope. After 1 hour incubation, the cells were in the process of adhesion and spreading on the prepared surfaces. After 3 hours, the cells on all prepared surfaces were further spreaded and flattened, however on the blasted and alkali treated surfaces, the cells exhibited slightly irregular shapes and some gaps or spaces were seen. After 24 hours incubation, most cells of the all groups had a flattened and polygonal shape, but the cells were more spreaded on the machined surfaces than the blasted and alkali treated surfaces. The MTT assay indicated the increase on machined, alkali treated and blasted surfaces according to time, and the alkali treated and blasted surfaces showed significantly increased in optical density comparing with machined surfaces at 1 day (p<0.01). Gene expression study showed that mRNA expression level of ${\alpha}\;1(I)$ collagen, alkaline phosphatase and osteopontin of the osteoblast-like cells showed a tendency to be higher on blasted and alkali treated surfaces than on the machined surfaces, although no siginificant difference in the mRNA expression level of ${\alpha}\;1(I)$ collagen, alkaline phosphatase and osteopontin was observed among all groups. In conclusion, we suggest that submicroscaled surfaces on osteoblast-like cell response do not over-ride the one of the surface with micro-scaled topography produced by blasting method, although the microscaled and submicro-scaled surfaces can accelerate osteogenic cell attachment and function compared with the machined surfaces.
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