• Title/Summary/Keyword: Immune cell infiltration

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The Effects of Cynanchi wilfordii Radix Ethanol Extracts upon Irradiated Rat's Blood and Organ (백하수오 에탄올추출물이 방사선조사에 따른 흰쥐의 혈구 및 장기에 미치는 영향)

  • Kim, Jang-Oh;Choi, Jun-Hyeok;Shin, Ji-Hye;Jung, Do-Young;Min, Byung-In
    • Journal of radiological science and technology
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    • v.39 no.3
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    • pp.451-459
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    • 2016
  • The development of radioprotector is being actively conducted in order to reduce the damage from over radiation exposure at radiation accident or radiation therapy. So this study was confirmed for radiation protective effects using the Cynanchi wilfordii Radix that has been known to be effective for antioxidant activity, anti-cancer, immune enhancing effects. The method of this study was administered orally Cynanchi wilfordii Radix ethanol extracts to Sprague Dawley Rat(SD Rat) for 14 days once a day, while measuring changed blood cell, spleen index, liver and uterus tissue along the change in time of 1, 4, 7 and 21 days after X-ray beam of 7 Gy irradiation. As the result of the experiment, the experimental group's rats which are administered with Cynanchi Wilfordii Radix ethanol extracts showed a rapid recovery in white blood cell count(p < 0.05) and spleen index(p < 0.05). In addition, condensation of nuclei, cytoplasmic swelling, and inflammatory cell infiltration in experimental group's liver cell was decreased more than in irradiation group's component. Further, experimental group's Uterine gland decreased the apoptosis more than irradiation group's components did. It is expected that Cynanchi Wilfordii Radix extracts will be useful as a new radioprotector. With above in mind, this paper may provide appropriate implications with the field of emergency management such as radiation accident.

Effects of Tumor Microenvironmental Factors on DNA Methylation and Radiation Sensitivity in A549 Human Lung Adenocarcinoma

  • Oh, Jung-Min;Kim, Young-Eun;Hong, Beom-Ju;Bok, Seoyeon;Jeon, Seong-Uk;Lee, Chan-Ju;Park, Dong-Young;Kim, Il Han;Kim, Hak Jae;Ahn, G-One
    • Journal of Radiation Protection and Research
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    • v.43 no.2
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    • pp.66-74
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    • 2018
  • Background: Tumor response to anticancer therapies can much be influenced by microenvironmental factors. In this study, we determined the effect of these microenvironmental factors on DNA methylation using A549 human lung adenocarcinoma cell line. Materials and Methods: We subjected A549 cells to various conditions mimicking tumor microenvironment including hypoxia, acidosis (sodium lactate), oxidative stress ($H_2O_2$), bystander effect (supernatant from doxorubicin (Dox)-treated or irradiated cells), and immune cell infiltration (supernatant from THP-1 or Jurkat T cells). Genomic DNA was isolated from these cells and analyzed for DNA methylation. Clonogenic cell survival, gene expression, and metabolism were analyzed in cells treated with some of these conditions. Results and Discussion: We found that DNA methylation level was significantly decreased in A549 cells treated with conditioned media from Dox-treated cells or Jurkat T cells, or sodium lactate, indicating an active transcription. To determine whether the decreased DNA methylation affects radiation sensitivity, we exposed cells to these conditions followed by 6 Gy irradiation and found that cell survival was significantly increased by sodium lactate while it was decreased by conditioned media from Dox-treated cells. We further observed that cells treated with conditioned media from Dox-treated cells exhibited significant changes in expression of genes including BAX and FAS (involved in apoptosis), NADPH dehydrogenase (mitochondria), EGFR (cellular survival) and RAD51 (DNA damage repair) while sodium lactate increased cellular metabolism rather than changing the gene expression. Conclusion: Our results suggest that various tumor microenvironmental factors can differentially influence DNA methylation and hence radiosensitivity and gene expression in A549 cancer cells.

IgG4 Related Disease Misdiagnosed to Carotid Body Tumor (경동맥소체종양으로 오인된 IgG4 연관 질환)

  • Lee, Gun Hyuk;Song, Ji-Sun;Yoon, So Yeon;Cho, Youn Jin;Hong, Hyun Jun
    • Korean Journal of Head & Neck Oncology
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    • v.36 no.2
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    • pp.27-31
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    • 2020
  • Neck mass has various etiologies, including inflammatory, congenital, neoplastic causes. The IgG4-related disease can cause symptoms in the head and neck areas with an inflammatory neck mass. It also shows clinical and pathological findings from inflammation caused by immune reactions, such as lymphocyte and plasma cell infiltration, storiform fibrosis, obliteration phlebitis, and invigorated serum IgG4 levels. The treatment guideline has not been established and still under debate, but systemic glucocorticoid seems to be effective in the most cases. In this brief report, a 48-year-old male patient presented with voice change for 3 weeks. Left side paramedian vocal fold palsy was observed in the flexible laryngoscopy. About 2.5×2.0×1.2cm size, heterogeneously enhanced neck mass with irregular margin encasing left carotid artery was noted on preoperative contrast enhanced neck CT scan, and it was suspicious of left carotid body tumor. The pathology shows IgG4-related disease rather than carotid body tumors. We report this case of IgG4-related disease, which can be misdiagnosed to carotid body tumors.

Inhibitory Effect of 3-(4-Hydroxyphenyl)-1-(thiophen-2-yl) prop-2-en-1-one, a Chalcone Derivative on MCP-1 Expression in Macrophages via Inhibition of ROS and Akt Signaling

  • Kim, Mi Jin;Kadayat, Taraman;Um, Yeon Ji;Jeong, Tae Cheon;Lee, Eung-Seok;Park, Pil-Hoon
    • Biomolecules & Therapeutics
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    • v.23 no.2
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    • pp.119-127
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    • 2015
  • Chalcones (1,3-diaryl-2-propen-1-ones), a subfamily of flavonoid, are widely known to possess potent anti-inflammatory and anti-oxidant properties. In this study, we investigated the effect of 3-(4-Hydroxyphenyl)-1-(thio3-(4-Hydroxyphenyl phen-2-yl)prop-2-en-1-one (TI-I-175), a synthetic chalcone derivative, on endotoxin-induced expression of monocyte chemoattractant protein-1 (MCP-1), one of the key chemokines that regulates migration and infiltration of immune cells, and its potential mechanisms. TI-I-175 potently inhibited MCP-1 mRNA expression stimulated by lipopolysaccharide (LPS) in RAW 264.7 macrophages without significant effect on cell viability. Treatment of cells with TI-I-175 markedly prevented LPS-induced transcriptional activation of activator protein-1 (AP-1) as measured by luciferase reporter assay, while nuclear factor-${\kappa}B$ (NF-${\kappa}B$) activity was not inhibited by TI-I-175, implying that TI-I-175 suppressed MCP-1 expression probably via regulation of AP-1. In addition, TI-I-175 treatment significantly inhibited LPS-induced Akt phosphorylation and led to a significant decrease in reactive oxygen species (ROS) production by LPS, which act as up-stream signaling events required for AP-1 activation in RAW 264.7 macrophages. Taken together, these results indicate that TI-I-175 suppresses MCP-1 gene expression in LPS-stimulated RAW 264.7 macrophages via suppression of ROS production and Akt activation.

Pathologic studies in lymph nodes of pigs infected with porcine circovirus type 2, porcine reproductive and respiratory syndrome virus (돼지 써코바이러스 2형과 돼지 생식기 호흡기 증후군 바이러스 감염에 따른 림프절 병변에 대한 병리학적 연구)

  • Jung, Ji-Youl;Kim, Jae-Hoon
    • Korean Journal of Veterinary Research
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    • v.53 no.4
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    • pp.245-251
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    • 2013
  • Porcine circovirus type 2 (PCV2) and porcine reproductive and respiratory syndrome virus (PRRSV) have been suspected to have immunosuppressive effects on pigs. To investigate the correlation between these virus infection and the lesions of lymph nodes including sub-mandibular and inguinal lymph node, 44 pigs (PCV2 single, n = 14; PRRSV single, n = 10; PCV2/PRRSV, n = 14; negative control, n = 6) were examined by histopathology and immunohistochemistry. Histopathologically, granulomatous lymphadenitis characterized by lymphoid depletion with histiocytic cells infiltration was observed in PCV-2 single and PCV-2/PRRSV group. Immunohistochemically, there were significant reduction of B and T lymphocytes in lymph nodes of these groups, while the number of macrophages was increased. In only PRRSV infected group, germinal center hypertrophy and lymphoid necrosis were observed. Immunohistochemically, the number of CD3+ T lymphocytes was slightly increased. Severe lymphocytic depletion in PCV-2 infection-related lymph nodes might be associated with producing immunocompromised state in pig. Comparing with PCV-2 infected group, PRRSV produced minor effects on the changes in immune cell population in the lymph nodes of pigs. PRRSV may increase susceptibility of the disease in pigs by disruption of the first defense lines in target organs, such as the alveolar macrophages in lungs.

Effect of Jasinwhalhyul-tang on MRL/MpJ-Ipr/Ipr Mouse Model with Systemic Lupus Erythematosus (자심활혈탕(滋腎活血湯)이 전신성홍반성낭창(全身性紅斑性狼蒼) 동물모델에 미치는 영향(影響))

  • Choi, Hoon-Seob;Cho, Chung-Sik;Kim, Cheol-Jung
    • The Journal of Korean Medicine
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    • v.29 no.1
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    • pp.67-84
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    • 2008
  • Objective : The main purpose of this study was to evaluate the effect of Jasinwhalhyul-tang (Zishenhuoxue-tang, JWT) on MRL/MpJ-Ipr/Ipr mouse model with systemic lupus erythematosus. Methods: The effect of JWT on MRL/MpJ-Ipr/Ipr mice that have autoimmune disease similar to SLE in humans was evaluated after JWT per oral in the present study. Mice were administered with Jasinwhalhyul-tang (Zishenhuoxue-tang, JWT) (80 or 400mg/kg) or distilled water for control group from experimental week 10 for 22 weeks. Results : The amount of erythematosus skin lesion and proteinuria were significantly decreased. The size and weight of cervical lymph nodes and spleen were significantly reduced. The ratio between activated $CD3^+CD69^+$ T-cells and undifferentiated $CD3^+CD4^-CD8^-$ T-cells in lymph nodes, spleen and kidney was effectively reduced. The gene expression of TGF-$\beta$ in spleen and kidney was increased. The amount of anti-dsDNA IgG in blood was decreased. The gene expression of TGF-$\beta$ in normal mouse spleen cells was increased depending on concentration by treatment of with T cell stimulating agent. In the histological examination of skin and kidney, the amount of infiltration of immune cells involved in the inflammatory response was decreased. Conclusions : According to the above results, JWT should be considered as an applicable therapeutic agent to SLE in clinical practice. Further research is required to investigate other efficacies of JWT on SLE.

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Diosmetin and Its Glycoside, Diosmin, Improve Atopic Dermatitis-Like Lesions in 2,4-Dinitrochlorobenzene-Induced Murine Models

  • Park, Sang-a;Bong, Sim-Kyu;Lee, Jin Woo;Park, No-June;Choi, Yongsoo;Kim, Sang Moo;Yang, Min Hye;Kim, Yong Kee;Kim, Su-Nam
    • Biomolecules & Therapeutics
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    • v.28 no.6
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    • pp.542-548
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    • 2020
  • Naturally derived diosmetin and its glycoside diosmin are known to be effective in treating inflammatory disease. This study was performed to determine whether diosmin and diosmetin have the effect of improving atopic dermatitis in a 2,4-dinitrochlorobenzen (DNCB)-induced atopic dermatitis (AD) model. DNCB was used to establish AD model in hairless mice. Skin moisture, serum immunoglobulin E (IgE), interleukin 4 (IL-4), and histological analysis were performed to measure the effectiveness of diosmin and diosmetine to improve AD. IL-4 levels were also measured in RBL-2H3 cells. Administration of diosmetin or diosmin orally inhibited the progress of DNCB-induced AD-like lesions in murine models by inhibiting transdermal water loss (TEWL) and increasing skin hydration. Diosmetin or diosmin treatment also reduced IgE and IL-4 levels in AD-induced hairless mouse serum samples. However, in the in vitro assay, only diosmetin, not diosmin, reduced the expression level of IL-4 mRNA in RBL-2H3 cells. Diosmin and diosmetine alleviated the altered epidermal thickness and immune cell infiltration in AD. Diosmin is considered effective in the cure of AD and skin inflammatory diseases by being converted into diosmetin in the body by pharmacokinetic metabolism. Thus, oral administration of diosmetin and diosmin might be a useful agent for the treatment of AD and cutaneous inflammatory diseases.

DNA chip Analysis of Psoriatic Skin during the Oriental Remedy (DNA chip을 이용한 건선의 한방치료에 관한 유전체 연구)

  • Kim Byoung Soo;Lee Sang Keun;Kim Hyun Woong;Lee Jeung Hoon;Lim Jong Soon;Kang Jung Soo
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.18 no.2
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    • pp.468-473
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    • 2004
  • Psoriasis is a chronic inflammatory disease of the skin characterized by epidermal hyperplasia, dermal angiogenesis, infiltration of activated T cells, and increased cytokine levels, and affects 1-3% of the world-wide population. Although many immunological and clinical reports indicate a role for the immune system in the pathogenesis of psoriasis, puzzling questions about psoriasis remain unsolved. During the several decade, immunosuppressor and PUVA treatment are ubiquitously used to psoriasis therapy. But recently, to promote terminal differentiation of keratinocytes, block either NK-Tcell or T-cell activation, and interrupting the angiogenic switch represent another therapeutic opportunity in psoriasis. To keep face with immunological therapy, the needs of newly designed prescription on the psoriasis treatments were demanded. With the object of understand the psoriasis from an orient medical point of view, patients were administrated the GY during several weeks. We investigated the changes of gene expression in involved and uninvolved skin samples during the oriental remedy. Microarray data showed several important results. First, Gene expression profiling is similar to each patient. Second, precursor proteins that organize cornified envelops are decreased at the end of remedy. But genes which related to apoptosis, G-protein signalling, and lipid metabolism are increased. Third, 68.5% of clustering genes localized on the psoriasis susceptibility locus. In our results indicated that GY influence on the keratinocytes hyperproliferation by regulating the gene, which located on the psoriasis susceptibility locus.

Effects of Sayeok-tang on Papain-Induced Osteoarthritis in Mice (Papain으로 유도된 골관절염 생쥐 모델에서 사역탕(四逆湯)의 항골관절염 효능에 관한 연구)

  • Kung, Shyang En;Oh, Min Seok
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.27 no.2
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    • pp.212-224
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    • 2013
  • This study intends to clarify how Sayeok-tang(here in after reffered to SYT) affect C57BL/10 mice whose osteoarthritis was induced by papain. Osteoarthritis was induced by injecting papain in the knee joint of 3 groups(n=6) of mice. Normal group was non-treatment group and was not injected papain, whereas control mice were orally administered with $200{\mu}{\ell}$ of physiological saline. Positive comparison group was medicated with 100 mg/kg of Joins$^{(R)}$ mixed with $200{\mu}{\ell}$ of physiological saline. Experimental group was medicated with 400 mg/kg of SYT mixed with $200{\mu}{\ell}$ of physiological saline. Both Positive and experimental comparison groups were orally medicated once per day for 4 weeks. After the experiment, the functions of liver and kidney, inflammation cytokine values within serum, degree of revelation for inflammation cytokine genes, immune cells within blood, metabolism of arachidonic acid and amount of cartilage were measured and histopathological changes in the knee joint structures were observed. As results, SYT had no significant effect on the liver and kidney functions. Interleukin-$1{\beta}$(IL-$1{\beta}$), interleukin-6(IL-6), monocyte chemo attractant protein-1(MCP-1) and tumor necrosis factor-${\alpha}$(TNF-${\alpha}$) were significantly decreased. Inflammation cytokines in joints were all significantly decreased. Prostaglandin $E_2(PGE_2)$, thromboxane $B_2(TXB_2)$ were significantly decreased. Destruction of cartilage on micro computed tomography(CT)-arthrography was meaningfully decreased. In terms of histopathology, infiltration of inflammation, proliferation of synovial membrane, subsidence of cartilage and bone due to penetration of excessive formation of synovial cell and destruction of cartilage were small. Based on all results mentioned above, Sayeok-tang(SYT) is believed to be meaningful for suppressing the progress of osteoarthritis and its treatments because of its anti-inflammatory effects and alleviation of pain with histopathological effective efficacy.

Effects of 1-fluoro-2,4 dinitrobenzene on Induction of Dermatitis in Mice (1-fluoro-2,4 dinitrobenzene처리 방법이 피부염 유발에 미치는 영향)

  • Kim, Mi Young;Kim, Han Na;Lee, Mi Ran;Kim, Byung Joo;Choi, Chan Hun;Jeoung, Hyun Woo;Kim, Hyung Woo
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.26 no.5
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    • pp.693-698
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    • 2012
  • This study was designed to investigate the effects of 1-fluoro-2,4 dinitrobenzene (DNFB) on Induction of dermatitis in mice. We investigated the effects of DNFB on induction of dermatitis in terms of changes in body weights, ear thickness, ear weight, spleen/body ratio, histopathological observation and cytokine productions in inflammed tissue of contact dermatitis (CD) mice. In our experiments, we induced CD by using two different methods. First, mice were sensitized and challenged on the back of each ear (topical induction). Second, mice were sensitized on shaved back and challenged back of each ear (systemic induction). In our results, average weights were lowered in both topical and systemic group. But, there was no statistical significance between topical and systemic group. Treatment with DNFB enlarged ear weights and thicknesses in both topical and systemic groups. In addition, both groups were showed almost same features such as immune cell infiltration, spongiosis and hyperplasia in histopathological observations. Finally production levels of TNF-a, IFN-g and IL-6 were markedly elevated in both topical and systemic groups. On the other hand, systemic induction was more effective in spleen/body ratio and IL-6 production compared to topical induction respectively. These results suggest that dermatitis model using DNFB was used as model of CD, not for atopic dermatitis model.