Kim, Yeon-Ju;Ji, Seung Taek;Kim, Da Yeon;Jung, Seok Yun;Kang, Songhwa;Park, Ji Hye;Jang, Woong Bi;Yun, Jisoo;Ha, Jongseong;Lee, Dong Hyung;Kwon, Sang-Mo
Molecules and Cells
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v.41
no.6
/
pp.582-590
/
2018
Endothelial progenitor cells (EPCs) and outgrowth endothelial cells (OECs) play a pivotal role in vascular regeneration in ischemic tissues; however, their therapeutic application in clinical settings is limited due to the low quality and quantity of patient-derived circulating EPCs. To solve this problem, we evaluated whether three priming small molecules (tauroursodeoxycholic acid, fucoidan, and oleuropein) could enhance the angiogenic potential of EPCs. Such enhancement would promote the cellular bioactivities and help to develop functionally improved EPC therapeutics for ischemic diseases by accelerating the priming effect of the defined physiological molecules. We found that preconditioning of each of the three small molecules significantly induced the differentiation potential of $CD34^+$ stem cells into EPC lineage cells. Notably, long-term priming of OECs with the three chemical cocktail (OEC-3C) increased the proliferation potential of EPCs via ERK activation. The migration, invasion, and tube-forming capacities were also significantly enhanced in OEC-3Cs compared with unprimed OECs. Further, the cell survival ratio was dramatically increased in OEC-3Cs against $H_2O_2$-induced oxidative stress via the augmented expression of Bcl-2, a pro-survival protein. In conclusion, we identified three small molecules for enhancing the bioactivities of ex vivo-expanded OECs for vascular repair. Long-term 3C priming might be a promising methodology for EPC-based therapy against ischemic diseases.
T cells play a key role in viral infection. However, in patients with chronic hepatitis C virus (HCV) infection, HCV-specific T cells are dysfunctional and impaired in the liver, which is the primary site for HCV replication. There are multiple potential mechanisms for HCV-specific T cell dysfunction including induction of immune inhibitory pathways (program death-1; PD-1, cytotoxic t lymphocyte associated antigen-4; CTLA-4) and immune tolerance induced specific for the liver. However, the interaction between hepatocytes and HCV-specific CD8 T cells has not clearly established. In this study, we confirmed huh (human hepatoma) 7.5 cells expressing HLA (human leukocyte antigen) A2 presented antigen to activate HCV-specific CD8 T cells in HLA A2-restricted manner and expression of PD-L (program death ligand) 1 on huh7.5 cells reduced HCV-specific CD8 T cell activation, suggesting an immune modulatory activity. Loss of HCV-specific tetramer responses following antigenic stimulation correlated with increased caspase-3 activity. In addition, PD-L1 on huh7.5 cells rescued HCV-specific CD8 T cells from apoptosis. Our results suggest that the interaction between PD-L1 and PD-1 can recover the function of HCV-specific CD8 T cells in the liver, which could be applied in therapy of HCV chronic infection.
Kim, Dae-Hee;Lee, Jong-Rok;Byun, Sung-Hui;Shin, Sang-Woo;Kwon, Young-Kyu;Kim, Sang-Chan
Journal of Physiology & Pathology in Korean Medicine
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v.20
no.4
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pp.902-908
/
2006
Tetrandra is the root of Stephania tetrandra 5. Moore (family Menispermaceae), or of Aristolochia frangchi Wu (family Aristolochiaceae). It is a Differ-flavored and cold-property herb acting on the urinary bladder, kidney and spleen meridiands. Known biological effects of this herb are expelling wind to relieve pain and inducing diuresis to alleviate edema. This herb also has anti-inflammatory and anti-hypersensitivity actions. Recent studies have shown that Stephanniae Tetrandrae Radix has antimicrobial effects, namely, a protective effect on acute renal failure induce by gentamicin sulfate and a suppressive effect against clostridium perfringes. However, there is a lack of studies concerning the immunological activities of this herb. The present study was conducted to evaluate the immunological activities of Stephanniae Tetrandrae Radix on the regulatory mechanisms of cytokines and nitric oxide (NO) in Raw 264.7 cells. Cell viability was measured by MTT assay after the treatment of Stephanniae Tetrandrae Radix extract (STRE) and NO production was monitored by measuring the nitrite content in culture medium. COX-2 and iNOS were determined by immunoblot analysis, and levels of cytokine were analyzed by sandwich immunoassays. Results provided evidences that STRE inhibited the production of nitrite and nitrate (NO), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) tumor necrosis $factor-{\alpha}\;(TNF-{\alpha})$, $interleukin-1{\beta}(IL-1{\beta})$ and interleukin-6 (IL-6) in Raw 264.7 cells activated with lipopolysaccharide (LPS). These findings showed that STRE could produce some anti-inflammatory effects which might play a role in adjunctive therapy in Gram-negative bacterial infections.
We reviewed retrospectively the medical records of 600 elderly patients, over 65 years old who visited oral medicine. The ratio of the age group was composed of 65${\sim}$74 years old group was 63.7%, 75${\sim}$84 years old group was 32.2%, over 85years old group was 4.2%, and the patients were mostly females. The main chief complaint was composed of oral soft tissue problem(44.1%) and oromaxillofacial pain(39.0%). The majority of systemic diseases was composed of diseases of the circulatory system(30.1%), diseases of the musculoskeletal system and connective tissue(16.8%), endocrine, nutritional and metabolic diseases, and diseases of the digestive system(10.1%). The numerous pateints were diagnosed as soft tissue disease(32.0%), arthrogenous disease(24.1%), and myogenous disease(18.1%) of temporomandibular disease.Principally medication(43.9%), physical therapy(24.2%) were performed. 14.2% of all patients visited oral medicine with a letter of request written by other medical departments or local dental clinics, or referred from other departments in Chosun university dental hospital. These findings indicate epidemiologic characteristics on the elderly patients visited oral medicine. We hope that this study will play a basis in the future research about the elderly patients.
Jo, Hannah;Eom, Young Woo;Kim, Hyun-Soo;Park, Hong Jun;Kim, Hee Man;Cho, Mee-Yon
Gut and Liver
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v.12
no.6
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pp.664-673
/
2018
Background/Aims: Regulatory dendritic cells (rDCs), which can be induced by mesenchymal stem cells (MSCs), play an important role in inducing and maintaining homeostasis of regulatory T cells and exhibit anti-inflammatory functions. In this study, we investigated whether MSCs could differentiate DCs into rDCs and compared the therapeutic effects of rDCs and MSCs on dextran sodium sulfate (DSS)-induced chronic colitis mice. Methods: Immature DCs (imDCs) and lipopolysaccharide (LPS)-treated mature DCs (mDCs) were co-cultured with MSCs for 48 hours, and then the profiles of surface markers and cytokines and regulatory roles of these DCs for primary splenocytes were analyzed. In addition, the therapeutic effects of MSCs and DCs co-cultured with MSCs were compared in chronic colitis mice. Results: After co-culture of imDCs (MSC-DCs) or LPS-treated mDCs (LPS+MSC-DCs) with MSCs, the expression of CD11c, CD80, CD86, interleukin 6 (IL-6), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), and interferon-${\gamma}$ (IFN-${\gamma}$), was decreased, but that of CD11b, IL-10, and transforming growth factor-${\beta}$ (TGF-${\beta}$) was increased. Furthermore, MSC-DCs and LPS+MSC-DCs induced the expression of CD4, CD25, and Foxp3 in primary splenocytes isolated from mice. In DSS-induced colitis mice, MSCs and MSC-DCs increased colon length, body weight, and survival rate and induced histological improvement. Moreover, in the colon tissues, the expression of IL-6, TNF-${\alpha}$, and IFN-${\gamma}$ decreased, but that of IL-10, TGF-${\beta}$, and Foxp3 increased in the MSC- and MSC-DC-injected groups. Conclusions: Our data suggest that MSCs differentiate DCs into rDCs, which ameliorate chronic colitis. Thus, rDCs stimulated by MSCs may be therapeutically useful for the treatment of chronic inflammatory diseases.
Kim, Mi-Young;Kruger, Annie J.;Jeong, Ju-Yeon;Kim, Jaehee;Shin, Phil kyung;Kim, Sun Young;Cho, Joo Young;Hahm, Ki Baik;Hong, Sung Pyo
Molecules and Cells
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v.42
no.6
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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.
The purpose of this study was to evaluate how accurately children with autism spectrum disorder (ASD; n = 9) recognized four basic emotions (i.e., happiness, sadness, anger, and fear) following musical or visual cues. Their performance was compared to that of typically developing children (TD; n = 14). All of the participants were between the ages of 7 and 13 years. Four musical cues and four visual cues for each emotion were presented to evaluate the participants' ability to recognize the four basic emotions. The results indicated that there were significant differences between the two groups between the musical and visual cues. In particular, the ASD group demonstrated significantly less accurate recognition of the four emotions compared to the TD group. However, the emotion recognition of both groups was more accurate following the musical cues compared to the visual cues. Finally, for both groups, their greatest recognition accuracy was for happiness following the musical cues. In terms of the visual cues, the ASD group exhibited the greatest recognition accuracy for anger. This initial study support that musical cues can facilitate emotion recognition in children with ASD. Further research is needed to improve our understanding of the mechanisms involved in emotion recognition and the role of sensory cues play in emotion recognition for children with ASD.
Medical image segmentation is the most important task in radiation therapy. Especially, when segmenting medical images, the liver is one of the most difficult organs to segment because it has various shapes and is close to other organs. Therefore, automatic segmentation of the liver in computed tomography (CT) images is a difficult task. Since tumors also have low contrast in surrounding tissues, and the shape, location, size, and number of tumors vary from patient to patient, accurate tumor segmentation takes a long time. In this study, we propose a method algorithm for automatically segmenting the liver and tumor for this purpose. As an advantage of setting the boundaries of the tumor, the liver and tumor were automatically segmented from the CT image using the 2D CoordConv DeepLab V3+ model using the CoordConv layer. For tumors, only cropped liver images were used to improve accuracy. Additionally, to increase the segmentation accuracy, augmentation, preprocess, loss function, and hyperparameter were used to find optimal values. We compared the CoordConv DeepLab v3+ model using the CoordConv layer and the DeepLab V3+ model without the CoordConv layer to determine whether they affected the segmentation accuracy. The data sets used included 131 hepatic tumor segmentation (LiTS) challenge data sets (100 train sets, 16 validation sets, and 15 test sets). Additional learned data were tested using 15 clinical data from Seoul St. Mary's Hospital. The evaluation was compared with the study results learned with a two-dimensional deep learning-based model. Dice values without the CoordConv layer achieved 0.965 ± 0.01 for liver segmentation and 0.925 ± 0.04 for tumor segmentation using the LiTS data set. Results from the clinical data set achieved 0.927 ± 0.02 for liver division and 0.903 ± 0.05 for tumor division. The dice values using the CoordConv layer achieved 0.989 ± 0.02 for liver segmentation and 0.937 ± 0.07 for tumor segmentation using the LiTS data set. Results from the clinical data set achieved 0.944 ± 0.02 for liver division and 0.916 ± 0.18 for tumor division. The use of CoordConv layers improves the segmentation accuracy. The highest of the most recently published values were 0.960 and 0.749 for liver and tumor division, respectively. However, better performance was achieved with 0.989 and 0.937 results for liver and tumor, which would have been used with the algorithm proposed in this study. The algorithm proposed in this study can play a useful role in treatment planning by improving contouring accuracy and reducing time when segmentation evaluation of liver and tumor is performed. And accurate identification of liver anatomy in medical imaging applications, such as surgical planning, as well as radiotherapy, which can leverage the findings of this study, can help clinical evaluation of the risks and benefits of liver intervention.
Radiation therapy of human tissues, including bone tissue, is accompanied by side effects on normal tissues. It has a more lethal effect on stem cells, which play an essential role in tissue regeneration, including the basal cells constituting the tissue. In this study, the mouse parietal model, which implemented an artificial osteoradionecrosis model on the parietal region of the mouse, was artificially defected and then the bone regeneration was tested. In order to overcome the implemented osteoradionecrosis, a fibrin scaffold, widely used as a biomaterial, and stromal cell-derived factor-1 (SDF-1), which is used as a long-term treatment for damaged, were mixed to verify the osteoradionecrosis regeneration effect on the parietal of mouse. In order to expect a synergistic effect in the fibrin scaffolds, a fibrin scaffolds was prepared after maintaining the concentration of SDF-1 (1 ㎍/ml) in the fibrinogen solution. In this study, after artificially creating a osteoradionecrosis model in the parietal region of mouse, fibrin scaffolds were incorporated to analyze the effect of bone regeneration within 4 weeks, the initial stage of bone regeneration. In conclusion, the combined use of these two substances did not show a dramatic regenerative effect in inducing the regeneration of osteoradionecrosis in the parietal region of mouse. However, positive results were obtained that can be maintain the bone regeneration effect environment at the initial stage. Therefore, the combined use of the fibrin scaffold and SDF-1 is considered to be a suitable candidate for the effect of overcoming osteoradionecrosis.
The Journal of the Convergence on Culture Technology
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v.9
no.2
/
pp.67-71
/
2023
The purpose of this study is to investigate the effect of a community-based cognitive stimulation program on cognitive function and subjective memory in the elderly with mild cognitive impairment. This study was applied by selecting 15 users who understood the purpose of this study and agreed to participate in the shelter program for more than 3 months from April 2019 to August 2019 at the D Dementia Center in G located, Gyeonggi-do. The program consisted of a total of 36 cognitive stimulation programs 3 times a week a total of 3 months. Cognitive stimulation program stimulates cognitive function through various activities such as orientation reinforcement, cognitive training, recall, music, art, and physical play, and is used for the purpose of improving social function. It consists of folk songs, percussion instruments, national gymnastics, dance, games, and traditional games. As a result of the cognitive stimulation program, the average cognitive function increased by 2.13 points from 26.33 points before implementation to 28.46 points after implementation, and a statistically significant result was obtained (p=0.000). Subjective memory decreased by 3.53 points from the average of 7.13 points before the cognitive stimulation program was implemented to 3.60 points after the implementation, and a statistically significant result was obtained (p=0.000). It can be confirmed that this works. Dementia is leading to a cost burden, and congnitive function decreases the aqulity of life. It brings various burdens. It is necessary to study cognitive stimulation programs applied to various environments in the future.
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