Ursodeoxycholic acid (UDCA) is a non-toxic, hydrophilic bile acid in widespread clinical use mainly for acute and chronic liver disease. Recently, treatment with UDCA in hepatic graft-versus-host disease has been given in immunosuppressive therapy for improvement of the biochemical markers of cholestasis. Moreover, it has been reported that UDCA possesses immunomodulatory effects by the suppression of cytokine production. In the present study, we hypothesized that UDCA may inhibit the production of the pro-inflammatory cytokine, IL-1$\beta$, and nitric oxide (NO) in microglia. In the study, we found that 100 $\mu$ g/mL UDCA effectively inhibited these two pro-inflammatory factors at 24 hand 48 h, compared to the $A\beta$42-pretreated groups. These results were compared with the LPS+UDCA group to confirm the UDCA effect. As microglia can be activated by several stimulants, such as $A\beta$42, in Alzheimers brain and can release those inflammatory factors, the ability to inhibit or at least decrease the production of IL-1$\beta$ and NO in Alzheimers disease (AD) is essential. Using RT-PCR, ELISA and the Griess Reagent System, we therefore found that UDCA in $A\beta$42 pre-treated cultures played a significant role in suppressing the expression or the production of IL-1$\beta$ and NO. Similarly, lipopolysaccharide (LPS) did not activate microglia in the presence of UDCA. Moreover, we found that UDCA exhibits a prolonged effect on microglial cells (up to 48 h), which suggests that UDCA may play an important role in chronic cell damage due to this long effect. These results further imply that UDCA could be an important cue in suppressing the microglial activation stimulated by massive AD peptides in the AD progressing brain.
Le, Dai;Lim, Soyeon;Min, Kwang Wook;Park, Joon Woo;Kim, Youjoung;Ha, Taejeong;Moon, Kyeong Hwan;Wagner, Kay-Uwe;Kim, Jin Woo
Molecules and Cells
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v.44
no.3
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pp.168-178
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2021
The retinal pigment epithelium (RPE) forms a monolayer sheet separating the retina and choroid in vertebrate eyes. The polarized nature of RPE is maintained by distributing membrane proteins differentially along apico-basal axis. We found the distributions of these proteins differ in embryonic, post-natal, and mature mouse RPE, suggesting developmental regulation of protein trafficking. Thus, we deleted tumor susceptibility gene 101 (Tsg101), a key component of endosomal sorting complexes required for transport (ESCRT), in embryonic and mature RPE to determine whether ESCRT-mediated endocytic protein trafficking correlated with the establishment and maintenance of RPE polarity. Loss of Tsg101 severely disturbed the polarity of RPE, which forms irregular aggregates exhibiting non-polarized distribution of cell adhesion proteins and activation of epidermal growth factor receptor signaling. These findings suggest that ESCRT-mediated protein trafficking is essential for the development and maintenance of RPE cell polarity.
Purpose: Critically ill patients are frequently transferred from one point of care to a hospital that can provide a higher level of care. To achieve optimal treatment within the targeted window of time necessary for time-sensitive cases like major trauma, rapid transportation and decision making are essential. Transferred patients have often undergone radiologic imaging at the referring hospital. Examining these outside images is paramount. Therefore, this study was conducted to estimate the upload time of outside images. Methods: This retrospective study was conducted from January to April 2020. Patients transferred from other hospitals with digitally recorded CDs or DVDs of radiologic or diagnostic images were included. When the patients were registered at the emergency department reception desk, the digital images were transmitted to our picture archiving and communication system using transmission software. The time of upload and the numbers of digital images were recorded. The time interval from patient registration to the time of upload was calculated. Results: The median number of images was 688 in the trauma team activation (TTA) group (688 in the TTA group, 281 in the non-TTA trauma group, and 176 in the nontrauma group, respectively; P<0.001). The median upload time was 10 minutes. The longest upload time was 169 minutes. The upload time was more than 20 minutes in 12 cases (19.4%). Conclusions: Patients with major trauma bring more images than patients with other diseases. Unexpected delays (>20 minutes) were noted in approximately 20% of cases. It is necessary to minimize this time.
Localizing damages is an essential task to monitor the health of the structures since they may not be able to operate anymore. Among the damage detection techniques, non-destructive methods are considerably more preferred than destructive methods since damage can be located without affecting the structural integrity. However, these methods have several drawbacks in terms of detecting abilities, time consumption, cost, and hardware or software requirements. Employing artificial intelligence techniques could overcome such issues and could provide a powerful damage detection model if the technique is utilized correctly. In this study, the crack localization in flat and folded plate structures has been conducted by employing a Backpropagated Artificial Neural Network (BPANN). For this purpose, cracks with 18 different dimensions in thin, flat, and folded structures having 150, 300, 450, and 600 folding angle have been modeled and subjected to free vibration analysis by employing the Classical Plate Theory with Finite Element Method. A Four-nodded quadrilateral element having six degrees of freedom has been considered to represent those structures mathematically. The first ten natural frequencies have been obtained regarding healthy and cracked structures. To localize the crack, the ratios of the frequencies of the cracked flat and folded structures to those of healthy ones have been taken into account. Those ratios have been given to BPANN as the input variables, while the crack locations have been considered as the output variables. A total of 500 crack locations have been regarded within the dataset obtained from the results of the free vibration analysis. To build the best intelligent model, a feature search has been conducted for BAPNN regarding activation function, the number of hidden layers, and the number of hidden neurons. Regarding the analysis results, it is concluded that the BPANN is able to localize the cracks with an average accuracy of 95.12%.
The γδ T cells are unconventional lymphocytes that function in both innate and adaptive immune responses against various intracellular and infectious stresses. The γδ T cells can be exploited as cancer-killing effector cells since γδ TCRs recognize MHC-like molecules and growth factor receptors that are upregulated in cancer cells, and γδ T cells can differentiate into cytotoxic effector cells. However, γδ T cells may also promote tumor progression by secreting IL-17 or other cytokines. Therefore, it is essential to understand how the differentiation and homeostasis of γδ T cells are regulated and whether distinct γδ T cell subsets have different functions. Human γδ T cells are classified into Vδ2 and non-Vδ2 γδ T cells. The majority of Vδ2 γδ T cells are Vγ9δ2 T cells that recognize pyrophosphorylated isoprenoids generated by the dysregulated mevalonate pathway. In contrast, Vδ1 T cells expand from initially diverse TCR repertoire in patients with infectious diseases and cancers. The ligands of Vδ1 T cells are diverse and include the growth factor receptors such as endothelial protein C receptor. Both Vδ1 and Vδ2 γδ T cells are implicated to have immunotherapeutic potentials for cancers, but the detailed elucidation of the distinct characteristics of 2 populations will be required to enhance the immunotherapeutic potential of γδ T cells. Here, we summarize recent progress regarding cancer immunology of human γδ T cells, including their development, heterogeneity, and plasticity, the putative mechanisms underlying ligand recognition and activation, and their dual effects on tumor progression in the tumor microenvironment.
Even now, 119 rescue services have dissatisfactory aspects in operation, system and equipments as discussed above, It is the most urgent subject to systemize rescue services so that they can be suitable for our status, for we will make 21C welfare state come true before long. So, this author suggest that the followings have to be raised to activate 119 rescue service. 1) Bring up experts and offer high-quality rescue service 2) Prepare more up-to-date equipments 3) Operate transfer joint organizations 4) Promote the ability to meet with a press at the time of rescue service activities 5) Adjust regulations related to rescue services 6) Make up for a countermeasure to traffic accidents of ambulances 7) Adjust regulations making it mandatory to establish heliport at the target on hospitals more than a defined scale 8) Install more rescue service teams 9) Educate and train officials belonging to briefing rooms, where the officials with long experiences are arranged 10) Minimize the time for rescue team to reach fields 11) Establish legal protection system for rescue the team Nowadays, our country operates the department of fire fighting and rescue services without great difficulty, even though the circumstances are bad - insufficient members and the inferior circumstances. All of the fire fighting officials are given heavy duties in bad circumstances, and so are the team of rescue service. The rescue service team, taking charge of some emergency medical system, do a fire fighting inspection as a non-duty service, though they are scanty of sleep due to prevention and protection services of the fire fighting service team. But, they can not engage in rescue services completely and have to deal with miscellaneous duties. So they can not offer professional emergency medical services. But now, almost every fire fighting organization, belonging to National Emergency Management Agency, are separating rescue services, which shows a lot of good results. People recognize rescue services to get better and better gradually and the demands for this rescue services increase. So, this is the best time when rescue service teams should offer qualitative services rather than quantitative services. The people will recognize this rescue service team to be an organization sacrificing and serving for them. However well institutes and operation systems should be established, the rescue service team can not come true their aim without strong wills that they will serve and sacrifice themselves for people from their hearts. In addition, it is essential for the officials in charge of policies about emergency medical services to have a concernment on and practice the policy without failure.
Kyeong, Kyu-Sang;Hong, Seung Hwa;Kim, Young Chul;Choi, Woong;Myung, Sun Chul;Lee, Moo Yeol;You, Ra Young;Kim, Chan Hyung;Kwon, So Yeon;Suzuki, Hikaru;Park, Yeon Jin;Jeong, Eun-Hwan;Kim, Hak Soon;Kim, Heon;Lim, Seung Woon;Xu, Wen-Xie;Lee, Sang Jin;Ji, Il Woon
The Korean Journal of Physiology and Pharmacology
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v.20
no.5
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pp.547-556
/
2016
Myometrial relaxation of mouse via expression of two-pore domain acid sensitive (TASK) channels was studied. In our previous report, we suggested that two-pore domain acid-sensing $K^+$ channels (TASK-2) might be one of the candidates for the regulation of uterine circular smooth muscles in mice. In this study, we tried to show the mechanisms of relaxation via TASK-2 channels in marine myometrium. Isometric contraction measurements and patch clamp technique were used to verify TASK conductance in murine myometrium. Western blot and immunehistochemical study under confocal microscopy were used to investigate molecular identity of TASK channel. In this study, we showed that TEA and 4-AP insensitive non-inactivating outward $K^+$ current (NIOK) may be responsible for the quiescence of murine pregnant longitudinal myometrium. The characteristics of NIOK coincided with two-pore domain acid-sensing $K^+$ channels (TASK-2). NIOK in the presence of $K^+$ channel blockers was inhibited further by TASK inhibitors such as quinidine, bupivacaine, lidocaine, and extracellular acidosis. Furthermore, oxytocin and estrogen inhibited NIOK in pregnant myometrium. When compared to non-pregnant myometrium, pregnant myometrium showed stronger inhibition of NIOK by quinidine and increased immunohistochemical expression of TASK-2. Finally, TASK-2 inhibitors induced strong myometrial contraction even in the presence of L-methionine, a known inhibitor of stretch-activated channels in the longitudinal myometrium of mouse. Activation of TASK-2 channels seems to play an essential role for relaxing uterus during pregnancy and it might be one of the alternatives for preventing preterm delivery.
Although water is an essential component of the human body and is involved in many physiological processes, the effect of a steady and sufficient water intake on blood components has not well elucidated. Therefore, we investigated the changes in hematological parameters, high-sensitivity C-reactive protein (hs-CRP), and immunoglobulin G (IgG) after water intake in 13 healthy adults. They were divided into two groups: The control group (N=4), which consumed water ad libitum, and the experimental group (N=9), which consumed 2 L of water per day. Two weeks later, blood cell counts, hematocrit, and hemoglobin content had increased in the experimental group, although not significantly (p>0.05); however, there was a significant increase in the mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) (p<0.05; and p<0.01, respectively), and a significant decrease in the mean platelet volume (MPV) (p<0.05). Of the immunologic parameters, a non-significant decrease in the concentration of hs-CRP, an indicator of cardiovascular disease risk, was observed (p>0.05). However, there was a dramatic and significant increase in the concentration of IgG (p<0.05). In conclusion, a steady and sufficient water intake may contribute to alleviate anemia by increasing hemoglobin. Additionally, it may decrease the risk of cardiovascular disease by decreasing platelet activation and concentration of hs-CRP. Furthermore, a steady intake of water may improve immune function by increasing the concentration of the components of humoral immunity.
Park, Jae-Eun;Lee, Ki-Young;Do, Su-Il;Lee, Sang-Soo
BMB Reports
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v.35
no.3
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pp.330-336
/
2002
The lgtB genes that encode $\beta$-1,4-galactosyltransferases from Neisseria meningitidis ATCC 13102 and gonorrhoeae ATCC 31151 were isolated by a polymerase chain reaction using the pfu DNA polymerase. They were expressed under the control of lac and T7 promoters in Escherichia coli M15 and BL21 (DE3). Although the genes were efficiently expressed in E. coli M15 at $37^{\circ}C$ (33 kDa), most of the $\beta$-1,4-galactosyltransferases that were produced were insoluble and proteolysed into enzymatically inactive polypeptides that lacked C-terminal residues (29.5 kDa and 28 kDa) during the purification steps. When the temperature of the cell growth was lowered to $25^{\circ}C$, however, the solubility of the $\beta$-1,4-galactosyltransferases increased substantially. A stable N-terminal his-tagged recombinant enzyme preparation could be achieved with E. coli BL21 (DE3) that expressed lgtB. Therefore, the cloned $\beta$-1,4-galactosyltransferases were expressed under the control of the T7 promoter in E. coli BL21 (DE3), mostly to the soluble form at $25^{\circ}C$. The proteins were easily purified to homogeneity by column chromatography using Ni-NTA resin, and were found to be active. The galactosyltransferases exhibited pH optimum at 6.5-7.0, and had an essential requirement for the $Mn^{+2}$ ions for its action. The $Mg^{+2}$ and $Ca{+2}$ ions showed about half of the galactosyltransferase activities with the $Mn^{+2}$ ion. In the presence of the $Fe^{+2}$ ion, partial activation was observed with the $\beta$-1,4-galactosyltransferase from N. meningitidis(64% of the enzyme activity with the $Mn^{+2}$$Ni^{+2}$, $Zn^{+2}$, and $Cu^{+2}$ ions could not activate the $\beta$-1,4-galactosyltransferase activity. The inhibited enzyme activity with the $Ni^{+2}$ ion was partially recovered with the $Mn^{+2}$$Fe^{+2}$, $Zn^{+2}$, and $Cu^{+2}$ ions, the $Mn^{+2}$$\beta$-1,4-galactosyltransferase activity was 1.5-fold stimulated with the non-ionic detergent Triton X-100 (0.1-5%).
Kim, E-Wan;Lee, Jin-Woo;Lee, Chang-Hee;Yea, Byeong-Deok
Journal of the Korean Society of Marine Environment & Safety
/
v.23
no.6
/
pp.628-638
/
2017
In response to difficult employment conditions in the maritime industry and a desire to expand their career options, domestic mates are persuing DP operator training at institutions both domestically and abroad based on their shipboard experience. However, since the offshore plant service industry has not yet been established in Korea, those seeking to enter this field have difficulty acquiring qualifications and most seek work overseas for offshore shipping companies. Individuals wishing to work as DP operators are likely to face more conservative recruitment processes with overseas offshore shipping companies, focusing on career language restrictions as they will be non-native speakers relative to the foreign company, difficulty living in a multi-cultural environment, and lack of systematic information on essential job requirements. For these reasons, domestic mates have difficulty seeking jobs. Therefore, this study analyzes the capabilities and qualification required to be a DP operator to provide basic data for developing NCS standards representing a minimum level of competency. These standards can be applied by the government to develop plans for professional training for DP operators. In study, job classifications, competency standards and career development paths for DP operators have been proposed along with joint use of DP training vessels, to train specialized DP instructors. An NCS export model led by the government to activate professional training for DP operators is also presented.
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