• Title/Summary/Keyword: T-cell dysfunction

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Protective effects of Tat-DJ-1 protein against streptozotocin-induced diabetes in a mice model

  • Yeo, Hyeon Ji;Yeo, Eun Ji;Shin, Min Jea;Choi, Yeon Joo;Lee, Chi Hern;Kwon, Hyeok Yil;Kim, Dae Won;Eum, Won Sik;Choi, Soo Young
    • BMB Reports
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    • v.51 no.7
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    • pp.362-367
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    • 2018
  • A major feature of type 1 diabetes mellitus (T1DM) is hyperglycemia and dysfunction of pancreatic ${\beta}$-cells. In a previous study, we have shown that Tat-DJ-1 protein inhibits pancreatic RINm5F ${\beta}$-cell death caused by oxidative stress. In this study, we examined effects of Tat-DJ-1 protein on streptozotocin (STZ)-induced diabetic mice. Wild type (WT) Tat-DJ-1 protein transduced into pancreas where it markedly inhibited pancreatic ${\beta}$-cell destruction and regulated levels of serum parameters including insulin, alkaline phosphatase (ALP), and free fatty acid (FFA) secretion. In addition, transduced WT Tat-DJ-1 protein significantly inhibited the activation of $NF-{\kappa}B$ and MAPK (ERK and p38) expression as well as expression of COX-2 and iNOS in STZ exposed pancreas. In contrast, treatment with C106A mutant Tat-DJ-1 protein showed no protective effects. Collectively, our results indicate that WT Tat-DJ-1 protein can significantly ameliorate pancreatic tissues in STZ-induced diabetes in mice.

The Effect of Radiation Therapy on Cellular Immune Response in Patients with Squamous Cell Lung Carcinoma (폐암 환자에서 방사선치료가 세포성 면역반응에 미치는 영향)

  • Uh, Soo-Taek;Kim, Chul-Hyun;Chung, Yeon-Tae;Kim, Yong-Hun;Park, Choon-Sik;Lee, Hi-Bahl;Huh, Seung-Jae
    • Tuberculosis and Respiratory Diseases
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    • v.38 no.1
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    • pp.25-33
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    • 1991
  • The immune staus is known to be decreased in malignant disease and radiation therapy (RT), used as a therapeutic tool, further decrease this-attenuated immune status. We measured the number of peripheral lymphocytes, its subsets and lymphoblast transformation for PPD, PHA, monoclonal antibodies including anti-CD3 and anti-CD2 before and after RT in 19 patients with squamous cell lung cancer to search the fine mechanism behind the RT-induced attenuation of lymphoblast transformtion for mitogens and antigen. The results were as follows; 1) The number of lymphocytes and its subsets decreased significantly after RT, but the percentages of lymhocyte subsets did not change aftr RT except interleukin-2 receptor positive T lymphocytes. 2) The function of lymphoctes, measured by lymphoblast tranformation for PHA and PPD, decrased after RT and the compositions of PBMC used for lymphoblast transformtion were not different before and after RT. 3) The mitosis of lymphocytes to anti-CD2 or anti-CD3 decreased significantly after RT. And IL-2 plus anti-CD3 increased the mitosis than that of anti-CD3 only after RT, but before RT there was no difference. In conclusion, we suggested the fine mechanism behind the RT-induced attenuation of immune response might be the dysfunction of lymphocytes in terms of impaired synthesis of IL-2 rather than the decrease of circulating lymphocyte numbers.

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Rab25 Deficiency Perturbs Epidermal Differentiation and Skin Barrier Function in Mice

  • Jeong, Haengdueng;Lim, Kyung-Min;Goldenring, James R.;Nam, Ki Taek
    • Biomolecules & Therapeutics
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    • v.27 no.6
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    • pp.553-561
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    • 2019
  • Rab25, a member of the Rab11 small GTPase family, is central to achieving cellular polarity in epithelial tissues. Rab25 is highly expressed in epithelial cells of various tissues including breast, vagina, cervix, the gastrointestinal tract, and skin. Rab25 plays key roles in tumorigenesis, mainly by regulating epithelial differentiation and proliferation. However, its role in skin physiology is relatively unknown. In this study, we demonstrated that Rab25 knock-out (KO) mice show a skin barrier dysfunction with high trans-epidermal water loss and low cutaneous hydration. To examine this observation, we investigated the histology and epidermal differentiation markers of the skin in Rab25 KO mice. Rab25 KO increased cell proliferation at the basal layer of epidermis, whereas the supra-basal layer remained unaffected. Ceramide, which is a critical lipid component for skin barrier function, was not altered by Rab25 KO in its distribution or amount, as determined by immunohistochemistry. Notably, levels of epidermal differentiation markers, including loricrin, involucrin, and keratins (5, 14, 1, and 10) increased prominently in Rab25 KO mice. In line with this, depletion of Rab25 with single hairpin RNA increased the expression of differentiation markers in a human keratinocyte cell line, HaCaT. Transcriptomic analysis of the skin revealed increased expression of genes associated with skin development, epidermal development, and keratinocyte differentiation in Rab25 KO mice. Collectively, these results suggested that Rab25 is involved in the regulation of epidermal differentiation and proliferation.

Updates on the Immune Cell Basis of Hepatic Ischemia-Reperfusion Injury

  • Mi Jeong Heo;Ji Ho Suh;Kyle L. Poulsen;Cynthia Ju;Kang Ho Kim
    • Molecules and Cells
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    • v.46 no.9
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    • pp.527-534
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    • 2023
  • Liver ischemia-reperfusion injury (IRI) is the main cause of organ dysfunction and failure after liver surgeries including organ transplantation. The mechanism of liver IRI is complex and numerous signals are involved but cellular metabolic disturbances, oxidative stress, and inflammation are considered the major contributors to liver IRI. In addition, the activation of inflammatory signals exacerbates liver IRI by recruiting macrophages, dendritic cells, and neutrophils, and activating NK cells, NKT cells, and cytotoxic T cells. Technological advances enable us to understand the role of specific immune cells during liver IRI. Accordingly, therapeutic strategies to prevent or treat liver IRI have been proposed but no definitive and effective therapies exist yet. This review summarizes the current update on the immune cell functions and discusses therapeutic potentials in liver IRI. A better understanding of this complex and highly dynamic process may allow for the development of innovative therapeutic approaches and optimize patient outcomes.

Antioxidant and Cytoprotective Effects of Socheongja and Socheong 2, Korean Black Seed Coat Soybean Varieties, against Hydrogen Peroxide-induced Oxidative Damage in HaCaT Human Skin Keratinocytes (HaCaT 인간 피부 각질세포에서 과산화수소 유도 산화 손상에 대한 소청자 및 소총2호의 항산화 및 세포보호 효능)

  • Choi, Eun Ok;Kwon, Da Hye;Hwang, Hye-Jin;Kim, Kook Jin;Lee, Dong Hee;Choi, Yung Hyun
    • Journal of Life Science
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    • v.28 no.4
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    • pp.454-464
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    • 2018
  • Black soybeans are used as food sources as well as for traditional medicines because they contain an abundance of natural phenolic compounds. In this study, total phenolic contents (TPCs) of Korean black seed coat soybean varieties Socheongja (SCJ), Socheong 2 (SC2) and Cheongja 2 (CJ2) as well as their antioxidant capacities were investigated. Among them, TPCs were abundantly present in the order of CJ2$H_2O_2$-stimulated HaCaT human keratinocytes. Our results revealed that treatment with SCJ and SC2 prior to $H_2O_2$ exposure significantly increases the viability of HaCaT cells, indicating that the exposure of HaCaT cells to SCJ and SC2 conferred a protective effect against oxidative stress. SCJ and SC2 also effectively inhibited $H_2O_2$-induced apoptotic cell death through the blocking of mitochondrial dysfunction. SCJ and SC2 also attenuated the phosphorylation of Histone H2AX. Furthermore, they effectively induced the levels of thioredoxin reductase (TrxR) 1, a potent antioxidant enzyme, which is associated with the induction of nuclear transcription factor erythroid-2-like factor 2 (Nrf2); however, the protective effects of SCJ and SC2 were significantly reversed by Auranofin, a TrxR inhibitor. These results indicate that they have protective activity through the blocking of cellular damage related to oxidative stress via the Nrf2 signaling pathway. In conclusion, our study indicated that SCJ and SC2 might potentially serve as novel agents for the treatment and prevention of skin disorders caused by oxidative stress.

Synthetic Cannabinoid-Induced Immunosuppression Augments Cerebellar Dysfunction in Tetanus-Toxin Treated Mice

  • Yun, Jaesuk;Gu, Sun Mi;Lee, Tac-hyung;Song, Yun Jeong;Seong, Seonhwa;Kim, Young-Hoon;Cha, Hye Jin;Han, Kyoung Moon;Shin, Jisoon;Oh, Hokyung;Jung, Kikyung;Ahn, Chiyoung;Park, Hye-Kyung;Kim, Hyung Soo
    • Biomolecules & Therapeutics
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    • v.25 no.3
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    • pp.266-271
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    • 2017
  • Synthetic cannabinoids are one of most abused new psychoactive substances. The recreational use of abused drug has aroused serious concerns about the consequences of these drugs on infection. However, the effects of synthetic cannabinoid on resistance to tetanus toxin are not fully understood yet. In the present study, we aimed to determine if the administration of synthetic cannabinoids increase the susceptibility to tetanus toxin-induced motor behavioral deficit and functional changes in cerebellar neurons in mice. Furthermore, we measured T lymphocytes marker levels, such as CD8 and CD4 which against tetanus toxin. JWH-210 administration decreased expression levels of T cell activators including cluster of differentiation (CD) $3{\varepsilon}$, $CD3{\gamma}$, CD74p31, and CD74p41. In addition, we demonstrated that JWH-210 induced motor impairment and decrement of vesicle-associated membrane proteins 2 levels in the cerebellum of mice treated with tetanus toxin. Furthermore, cerebellar glutamatergic neuronal homeostasis was hampered by JWH-210 administration, as evidenced by increased glutamate concentration levels in the cerebellum. These results suggest that JWH-210 may increase the vulnerability to tetanus toxin via the regulation of immune function.

Evaluation of Phototoxicity for Cosmetics and Alternative Method (화장품 광독성 평가와 동물대체시험법)

  • Lee, Jong-Kwon;Sin, Ji-Soon;Kim, Jin-Ho;Eom, Jun-Ho;Kim, Hyung-Soo;Park, Kui-Lea
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.31 no.3 s.52
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    • pp.245-251
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    • 2005
  • Safety is one of the key issue in the regulation of cosmetics. Cosmetic Act deals with it in Korea. The guidance for the testing cosmetic ingredients and their safety evaluation are prepared by Korea Food and Drug Administration. Ultraviolet radiation could Induce skin damage, edema, erythema, photoaging, immune dysfunction and skin cancer. Ultraviolet radiation is classified as Group 2A(probably carcinogenic to humans) by International Agenry for Reaserch on Cancer(IARC). The in vitro methodologies for evaluating the toxic potential of ingredients reported in the literature have not yet been sufficiently validated for use in areas other than the study for mutagenicity/genotoxicity, for pre-screening for severe irritancy, for screening of phototoxicity and for evaluating the percutaneous absorption. The 3T3 neutral red uptake photoxicity test (3T3 NRU PT) was accepted as OECD toxicity guideline in 2002. The 3T3 NRU PT is an in vitro method based on a comparison of the cytotoxicitv of a chemical when tested in the presence and in the absence of exposure to a non-cytotoxic dose of UVA/visible light.

Effect of blended protein nutritional support on reducing burn-induced inflammation and organ injury

  • Yu, Yonghui;Zhang, Jingjie;Wang, Jing;Wang, Jing;Chai, Jiake
    • Nutrition Research and Practice
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    • v.16 no.5
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    • pp.589-603
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    • 2022
  • BACKGROUND/OBJECTIVES: Previous studies have reported that protein supplementation contributes to the attenuation of inflammation. Serious trauma such as burn injury usually results in the excessive release of inflammatory factors and organs dysfunction. However, a few reports continued to focus on the function of protein ingestion in regulating burn-induced inflammation and organ dysfunction. MATERIALS/METHODS: This study established the rat model of 30% total body surface area burn injury, and evaluated the function of blended protein (mixture of whey and soybean proteins). Blood routine examination, inflammatory factors, blood biochemistry, and immunohistochemical assays were employed to analyze the samples from different treatment groups. RESULTS: Our results indicated a decrease in the numbers of white blood cells, monocytes, and neutrophils in the burn injury group administered with the blended protein nutritional support (Burn+BP), as compared to the burn injury group administered normal saline supplementation (Burn+S). Expressions of the pro-inflammatory factors (tumor necrosis factor-α and interleukin-6 [IL-6]) and chemokines (macrophage chemoattractant protein-1, regulated upon activation normal T cell expressed and secreted factor, and C-C motif chemokine 11) were dramatically decreased, whereas anti-inflammatory factors (IL-4, IL-10, and IL-13) were significantly increased in the Burn+BP group. Kidney function related markers blood urea nitrogen and serum creatinine, and the liver function related markers alanine transaminase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase were remarkably reduced, whereas albumin levels were elevated in the Burn+BP group as compared to levels obtained in the Burn+S group. Furthermore, inflammatory cells infiltration of the kidney and liver was also attenuated after burn injury administered with blended protein supplementation. CONCLUSIONS: In summary, nutritional support with blended proteins dramatically attenuates the burn-induced inflammatory reaction and protects organ functions. We believe this is a new insight into a potential therapeutic strategy for nutritional support of burn patients.

Effects of Gami-Shinkiwhan on the Reproductive Function of Male Aged Mice (가미신기환(加味腎氣丸)이 수컷 노화 생쥐의 생식기능에 미치는 영향)

  • Park, Sun Young;Ahn, Sang Hyun;Kim, Ho Hyun
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.31 no.6
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    • pp.367-373
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    • 2017
  • This study was performed using histochemical and immunohistochemical methods to investigate the effect of Gami-Shinkiwhan(GS) on reproductive function of male aged mice. 8-weeks-old ICR mice were used as control group, without any treatment, and 15-month-old ICR mice were used as aging elicited group(AE) and Gami-Shinkiwhan treatment group(GS). AE group didn't restrict diets and drinking for 6 months without any treatment. GS was administered 0.56g/kg/day for 6 months. Compared with AE group, the cell division of sertoli cells, spermatids, and spermatogonial cells was increased and the apoptosis of sertoli cells was decreased on GS group. Androgen receptor positive reaction and $17{\beta}$-HSD positive reaction were significantly increased in the GS group compared to AE group. In addition, the DJ-1 positive reaction was significantly increased and the HDAC3 positive response was significantly decreased in the GS group compared with AE group. Based on the above results, GS prevented the apoptosis of sertoli cells in the tubules, and increased the production of sertoli cells, spermatozoa and testosterone. Based on this, it is thought that it improves male reproductive dysfunction caused by late-onset hypogonadism.

Phenotypic Characterization of MPS IIIA (Sgshmps3a/ Sgshmps3a) Mouse Model

  • Park, Sung Won;Ko, Ara;Jin, Dong-kyu
    • Journal of mucopolysaccharidosis and rare diseases
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    • v.4 no.1
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    • pp.26-36
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    • 2018
  • Mucopolysaccharidosis IIIA is a heritable neurodegenerative disorder resulting from the dysfunction of the lysosomal hydrolase sulphamidase. This leads to the primary accumulation of the complex carbohydrate heparan sulphate in a wide range of tissues and CNS degeneration. Characterization of animal model is the beginning point of the therapeutic clinical trial. Mouse model has a limitation in that it is not a human and does not have all of the disease phenotypes. Therefore, delineate of the phenotypic characteristics of MPS IIIA mouse model prerequisite for the enzyme replace treatment for the diseases. We designed 6-month duration of phenotypic characterization of MPS IIIA mouse biochemically, behaviorally and histologically. We compared height and weight of MPS IIIA mouse with wild type from 4 weeks to 6 months in both male and female. At 6 months, we measured GAG storage in urine kidney, heart, liver, lung and spleen. The brain GAG storage is presented with Alcian blue staining, immunohistochemistry, and electron-microscopy. The neurologic phenotype is evaluated by brain MRI and behavioral study including open field test, fear conditioning, T-maze test and Y-maze test. Especially behavioral tests were done serially at 4month and 6month. This study will show the result of the MPS IIIA mouse model phenotypic characterization. The MPS IIIA mouse provides an excellent model for evaluating pathogenic mechanisms of disease and for testing treatment strategies, including enzyme or cell replacement and gene therapy.