• Title/Summary/Keyword: T cell survival

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Development of S-Methylmethionine Sulfonium Derivatives and Their Skin-Protective Effect against Ultraviolet Exposure

  • Kim, Won-Serk;Kim, Wang-Kyun;Choi, Nahyun;Suh, Wonhee;Lee, Jinu;Kim, Dae-Duk;Kim, Ikyon;Sung, Jong-Hyuk
    • Biomolecules & Therapeutics
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    • v.26 no.3
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    • pp.306-312
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    • 2018
  • In a previous study, we have demonstrated that S-methylmethionine sulfonium (SMMS) confers wound-healing and photoprotective effects on the skin, suggesting that SMMS can be used as a cosmetic raw material. However, it has an unpleasant odor. Therefore, in the present study, we synthesized odor-free SMMS derivatives by eliminating dimethyl sulfide, which is the cause of the unpleasant odor and identified two derivatives that exhibited skin-protective effects: one derivative comprised (2S,4S)- and (2R,4S)-2-phenylthiazolidine-4-carboxylic acid and the other comprised (2S,4R)-, (2S,4S)-, (2R,4R)-, and (2R,4S)-2-phenyl-1,3-thiazinane-4-carboxylic acid. We performed in vitro proliferation assays using human dermal fibroblasts (hDFs) and an immortalized human keratinocyte cell line (HaCaT). The two SMMS derivatives were shown to increase hDF and HaCaT cell proliferation as well as improve their survival by protecting against ultraviolet exposure. Moreover, the derivatives regulated the expression of collagen type I and MMP mRNAs against ultraviolet exposure in hDFs, suggesting that these derivatives can be developed as cosmetic raw materials.

Inhibitory Effects of Ethanol Extracts of Some Korean Plants on Ultraviolet B-Induced DNA Damage (HaCaT 세포에서 자외선 B에 의해 유도되는 DNA 상해에 대한 국내 수종 자생 식물 에탄올 추출물의 저해효과)

  • Lee, Seok Hee;Ha, Se Eun;Cho, Hyoung Kwon;Park, Jong Kun
    • The Korean Journal of Food And Nutrition
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    • v.27 no.5
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    • pp.845-850
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    • 2014
  • In the present study, the effects of extracts from Korean plants on the DNA damage response in HaCaT cells exposed to ultraviolet B (UVB) were investigated. The activity of cells treated for 24 hr with ethanol extracts from Vaccinium spp. (VS), and Vitis vinifera L (VV) alone was similar to that of the non-treated control, but gradually decreased at concentrations above $200{\mu}g/mL$. However, when post-incubation of UVB-exposed cells was carried out for 24 hr in medium containing VS or VV extracts, the cell activity increased in a concentration-dependent manner compared with that in the normal growth medium. The cell viability of UVB-exposed cells also increased when post-incubated in medium containing VS or VV extracts, in a concentration-dependent manner. Nuclear fragmentation analysis showed that post-incubation with VS or VV extracts decreased the UVB-induced apoptosis by about 10 and 13%, respectively, of that in cells post-incubated in growth medium. After 24 hr of post-incubation in medium containing VS or VV extracts, the level of CPD and 8-OHdG decreased in time- and concentration-dependent manners. Overall these results suggest that VS and VV extracts assist the survival of UVB-exposed cells, in accordance with the respective decrease in the levels of UVB-induced DNA damage.

Inhibition of mouse SP2/0 myeloma cell growth by the B7-H4 protein vaccine

  • Mu, Nan;Liu, Nannan;Hao, Qiang;Xu, Yujin;Li, Jialin;Li, Weina;Wu, Shouzhen;Zhang, Cun;Su, Haichuan
    • BMB Reports
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    • v.47 no.7
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    • pp.399-404
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    • 2014
  • B7-H4 is a member of B7 family of co-inhibitory molecules and B7-H4 protein is found to be overexpressed in many human cancers and which is usually associated with poor survival. In this study, we developed a therapeutic vaccine made from a fusion protein composed of a tetanus toxoid (TT) T-helper cell epitope and human B7-H4IgV domain (TT-rhB7-H4IgV). We investigated the anti-tumor effect of the TT-rhB7-H4IgV vaccine in BALB/c mice and SP2/0 myeloma growth was significantly suppressed in mice. The TT-rhB7-H4IgV vaccine induced high-titer specific antibodies in mice. Further, the antibodies induced by TT-rhB7-H4IgV vaccine were capable of depleting SP2/0 cells through complement-dependent cytotoxicity (CDC) in vitro. On the other hand, the poor cellular immune response was irrelevant to the therapeutic efficacy. These results indicate that the recombinant TT-rhB7-H4IgV vaccine might be a useful candidate of immunotherapy for the treatment of some tumors associated with abnormal expression of B7-H4.

Intranasal Immunization With Nanoparticles Containing an Orientia tsutsugamushi Protein Vaccine Candidate and a Polysorbitol Transporter Adjuvant Enhances Both Humoral and Cellular Immune Responses

  • Cheol Gyun Kim;Won Kyong Kim;Narae Kim;Young Jin Pyung;Da-Jeong Park;Jeong-Cheol Lee;Chong-Su Cho;Hyuk Chu;Cheol-Heui Yun
    • IMMUNE NETWORK
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    • v.23 no.6
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    • pp.47.1-47.16
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    • 2023
  • Scrub typhus, a mite-borne infectious disease, is caused by Orientia tsutsugamushi. Despite many attempts to develop a protective strategy, an effective preventive vaccine has not been developed. The identification of appropriate Ags that cover diverse antigenic strains and provide long-lasting immunity is a fundamental challenge in the development of a scrub typhus vaccine. We investigated whether this limitation could be overcome by harnessing the nanoparticle-forming polysorbitol transporter (PST) for an O. tsutsugamushi vaccine strategy. Two target proteins, 56-kDa type-specific Ag (TSA56) and surface cell Ag A (ScaA) were used as vaccine candidates. PST formed stable nano-size complexes with TSA56 (TSA56-PST) and ScaA (ScaA-PST); neither exhibited cytotoxicity. The formation of Ag-specific IgG2a, IgG2b, and IgA in mice was enhanced by intranasal vaccination with TSA56-PST or ScaA-PST. The vaccines containing PST induced Ag-specific proliferation of CD8+ and CD4+ T cells. Furthermore, the vaccines containing PST improved the mouse survival against O. tsutsugamushi infection. Collectively, the present study indicated that PST could enhance both Ag-specific humoral immunity and T cell response, which are essential to effectively confer protective immunity against O. tsutsugamushi infection. These findings suggest that PST has potential for use in an intranasal vaccination strategy.

Spontaneous Apoptosis and Metastasis in Squamous Cell Carcinoma of the Lung (폐 편평세포암에서 자발성 아포토시스와 원격전이)

  • Oh Yoon-Kyeong;Kee Keun-Hong
    • Radiation Oncology Journal
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    • v.17 no.3
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    • pp.203-208
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    • 1999
  • Purpose : To evaluate whether spontaneous apoptosis has prognostic value among patients with squamous cell carcinoma of lung. Materials and Methods : Material from 19 patients who received thoracic irradiation between 1990 and 1994 was analyzed. Their stages were II (1), IIIa (8), IIIb (5), and IV (5). Patients were observed from 5 to 67 months (median : 17 months). The spontaneous apoptosis index (AI) and p53 mutation were measured by immunohistochemical stains. Results : AI was found to range from 0 to $1\%$ (median $0.4\%$). Patients with low AI ($AI{\leq}$median) had a much higher distant metastasis rate at diagnosis than patients with high AI. By analysis of prognostic factors for survival, M stage was significant in univariate analysis. AI, chemotherapy, M stage, T stage, and stage were significant in multivariate analysis. The correlation between the AI and p53 mutation was not seen. Conclusion : AI was related with distant metastasis at diagnosis and not with p53 mutation. Also low AI group tended to have shorter survival time than high AI group.

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Bioactivities of feral peach (Prunus persica Batsch var. davidiana Max.) flower extracts and Prunus mume flower extracts (개복숭아꽃과 매화꽃 추출물의 생물활성)

  • Kim, Mijung;Park, Seyeon
    • Journal of Applied Biological Chemistry
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    • v.64 no.2
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    • pp.133-140
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    • 2021
  • In this study, we investigated the antibacterial, antioxidant, and whitening effects of Prunus persica Batsch var. davidiana Max. (Feral Peach) and Prunus mume (white and pink) flowers. The extracts of the three kinds of flowers showed antibacterial activity against Staphylococcus. aureus. The chloroform fractions of the white Prunus mume, Feral Peach, and pink Prunus mume flowers exhibited antibacterial activities of 84, 49, and 30%, respectively, against Staphylococcus. aureus at a concentration of 0.5 mg/mL. The flower extracts of the three species also exhibited antibacterial effects against Pseudomonas. aeruginosa. The chloroform fractions of the Feral Peach and pink Prunus meme flowers exhibited antibacterial activities of 36 and 30%, respectively, at a concentration of 0.5 mg/mL. These extracts did not exhibit any significant antibacterial activity against Staphylococcus. epidermidis and Escherichia. coli. The extracts of the three kinds of flowers did not significantly affect the survival of HaCaT cells. The distilled water fraction of the pink Prunus mume flower extract exhibited antioxidant effects at concentrations of both 20 and 40 ㎍/mL. The ethyl acetate fraction of the pink Prunus mume flower extract exhibited an antioxidant activity superior to glutathione at a concentration of 40 ㎍/mL. The flower extracts did not significantly affect the survival rate of B16F10 cells. The chloroform fraction of the Feral Peach flower exhibited a whitening effect of 18% at a concentration of 40 ㎍/mL. Based on these results, we conclude that the three kinds of flower extracts are raw materials exhibiting antibacterial, antioxidant, and whitening effects.

The estrogen-related receptor γ modulator, GSK5182, inhibits osteoclast differentiation and accelerates osteoclast apoptosis

  • Kim, Hyun-Ju;Yoon, Hye-Jin;Lee, Dong-Kyo;Jin, Xian;Che, Xiangguo;Choi, Je-Yong
    • BMB Reports
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    • v.54 no.5
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    • pp.266-271
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    • 2021
  • Estrogen-related receptor γ (ERRγ), a member of the orphan nuclear receptor family, is a key mediator in cellular metabolic processes and energy homeostasis. Therefore, ERRγ has become an attractive target for treating diverse metabolic disorders. We recently reported that ERRγ acts as a negative regulator of osteoclastogenesis induced by receptor activator of nuclear factor-κB ligand (RANKL). In the present study, we explored the effects of an ERRγ-specific modulator, GSK5182, on ERRγ-regulated osteoclast differentiation and survival. Interestingly, GSK5182 increased ERRγ protein levels much as does GSK4716, which is an ERRγ agonist. GSK5182 inhibited osteoclast generation from bone-marrow-derived macrophages without affecting cytotoxicity. GSK5182 also attenuated RANKL-mediated expression of cFos and nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), pivotal transcription factors for osteoclastogenesis. Arrested osteoclast differentiation was associated with reduced RANK expression, but not with the M-CSF receptor, c-Fms. GSK5182 strongly blocked the phosphorylation of IκBα, c-Jun N-terminal kinase, and extracellular signal-regulated kinase in response to RANKL. GSK5182 also suppressed NF-κB promoter activity in a dose-dependent manner. In addition to osteoclastogenesis, GSK5182 accelerated osteoclast apoptosis by caspase-3 activation. Together, these results suggest that GSK5182, a synthetic ERRγ modulator, may have potential in treating disorders related to bone resorption.

Prognosis of Patients with Non-Small Cell Lung Cancer after Surgery (비소세포 폐암 환자의 수술 후 예후)

  • Kang, Min-Jong;Park, Gye-Young;Yoo, Chul-Gyu;Chung, Hee-Soon;Kim, Young-Whan;Han, Sung-Koo;Shim, Young-Soo
    • Tuberculosis and Respiratory Diseases
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    • v.43 no.3
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    • pp.331-338
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    • 1996
  • Background : Lung cancer continues to be the leading cause of cancer death in the United States and it's incidence has been rapidly increasing in Korea, too. The overall cure rate for non-small cell lung cancer(NSCLC) is approximately 10%, and the cure is generally achieved by surgery. Unfortunately, however, less than 15% of all patients and less than 25% of those who present with localized disease are candidates for curative surgical resection. So preoperative staging evaluation followed by curative resection has a major role in determining the long tenn prognosis of NSCLC patients. Therefore, we have conducted this study to compare pre-operative and post-operative staging and the long-tenn relapse-free survival rates in NSCLC patients according to its stage. Methods : We analyzed the medical records of 217 NSCLC patients who were operated on for curative resection in Seoul National University Hospital, retrospectively. Among them, 170 patients who were completely resected were selected to determine the long term relapse-free survival rates. Results : Among 217 NSCLC patients, men were 157 and women were 30. The median age was 58 and the difference between men and women was not found. The discrepancy rate between preoperative and postoperative staging was 40.1%. Its major cause was due to the difference of nodal staging. The 3-year relapse-free survival rates were 73%, 53% and 48% in stage I, II and IIIa, respectively. There was no difference of relapse-free duration in recurred patients according to the stage or histologic types. Conclusion : The postoperative pathologic staging determines the long tenn prognosis of patients with NSCLC after surgery, but current preoperative clinical staging can not predict the postoperative pathologic staging correctly. So the improved modality of staging system is required to predict the pathologic staging more correctly.

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The Study on Acute.Subacute Toxicity and Anti-cancer Effect of H Herbal-acupuncture (H-약침(藥鍼)의 급성(急性).아급성(亞急性) 독성실험(毒性實驗) 및 항암효과(抗癌效果)에 관(關)한 실험적(實驗的) 연구(硏究))

  • Kim, Tae-Hui;Kwon, Ki-Rok;Lee, Seon-Goo
    • Journal of Pharmacopuncture
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    • v.5 no.2
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    • pp.120-136
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    • 2002
  • Objectives : The purpose of this study is to investigate Acute and Subacute Toxicity, and Anti-cancer Effect of H Herbal-acupuncture on mice and rats. Methods : Balb/c mice were injected intraperitoneally with H Herbal-acupuncture for $LD_{50}$ and acute toxicity test. Sprague-Dawley rats were experimented in the same way for subacute toxicity test. H Herbal-acupuncture was injected into abdomen of mice having S-180 cancer cell line. Result : 1. During the test, $LD_{50}$ could not be counted since there was no expired subjects. 2. In an acute toxicity test, the loss of motility and reflex action was observed, but weight increased in the treatment group, compared with those in the normal group (P<0.05). 3. In an acute toxicity test of serum biochemical values of mice, glucose increased in the treatment group II while total cholesterol was increased in the all treatment groups (P<0.05). 4. In a subacute toxicity test, a little loss of motility and reflex action was observed in the treatment group. Weight of mice in the treatment group decreased on the 28th day. 5. In a subacute toxicity test, liver weight was decreased but lung weight of mice increased in the all treatment groups (P<0.05). 6. As a result of measuring Complete Blood Count test (CBC) of rat, HCT was decreased in treatments even though it was not significant, compared with the normal group (P<0.05). 7. In a serum biochemical value test of subacute toxicity, total protein and albumin decreased in the all treatment groups. Creatinine, glucose, GOT increased in the treatment group I compared with the control group. Alkaline phos-phatase decreased in treatment II group, compared with the control group (P<0.05). 8. Median survival time that was measured in the rats treated with sarcoma-180 cancer cell Median decreased in the treatment group, compared with the control group (P<0.05). 9. Natural killer cell activity showed significant reduction at 100:1 and 10:1 E/T ratio while it increased at 50:1 E/T ratio. It is inferred that there was an error in the experiment (P<0.05). 10. In an interleukin-2 productivity test, even though it decreased in lung cancer, and increased in abdomen cancer, but it was only a small difference (P<0.005). 11. After injecting B16F10 cell into a capillary vessel of C57BL/6 mice and generating metastasized lung cancer, the lung was examined with the naked eye. It was not possible to see metastasized cancer in the all groups on the seventh day but the cancer was viewed on the fourteenth day. The number and volume of metastasized cancer in the treatment group enlarged in the treatment group, compared with the control group. Conclusion : According to the results, H herbal-acupuncture took no effects in cancer.

A study of Tumor Angiogenesis in Human Lung Cancer by Immunohistochemical Stain (Human Lung Cancer에서 면역세포화학적 방법을 이용한 Tumor Angiogenesis에 관한 연구)

  • Cheon, Seon Hee;Kim, Sung Sook;Rha, Sun Young;Chung, Hyun Cheol
    • Tuberculosis and Respiratory Diseases
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    • v.43 no.6
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    • pp.894-902
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    • 1996
  • Background : Tumor angiogenesis is the growth of new vessels toward and within tumor. It has been demonstrated that the growth of tumor beyond a certain size requires angiogenesis and it is closely involved in tumor progression and metastasis. The finding that intensity of neovascularization correlates independently with metastasis may lead to identification of patients in whom radical surgery should be supplemented by systemic treatment. Method : We have collected paraffin blocks of bronchoscopic biopsy of patients with non-small cell lung cancer. We highlighted the vessel by staining endothelial cell with JC70 monoclonal antibody(to CD31) immunohistochemically and counted microvessels under 200 X field using light microscopy. Results : 1) The mean microvessel count was $32.7{\pm}20.8$ (9-96) in total 29 cases. 2) There were no correlations between microvessel counts and pathologic cell type, T staging, node melastasis(N) and hematogenous metastasis(M) (p>0.05). 3) The median follow-up duration was 15 months(2-46) and there was no correlation between the microvessel counts and survival rate of lung cancer patients (p>0.05). Conclusion : Tumor angiogenesis seems to be an important prognostic factor suggesting the probability of metastasis. But the microvessel count in the bronchoscopic biopsy specimen was inadequate and very limited. There has been no data about angiogenesis of lung cancer in korea yet So the study of tumor angiogenesis using resected lung tumor specimen would be demanded.

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