• Title/Summary/Keyword: PD-L2

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Nrf2 in TIME: The Emerging Role of Nuclear Factor Erythroid 2-Related Factor 2 in the Tumor Immune Microenvironment

  • Jialin Feng;Oliver J. Read;Albena T. Dinkova-Kostova
    • Molecules and Cells
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    • v.46 no.3
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    • pp.142-152
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    • 2023
  • Nuclear factor erythroid 2-related factor 2 (Nrf2) mediates the cellular antioxidant response, allowing adaptation and survival under conditions of oxidative, electrophilic and inflammatory stress, and has a role in metabolism, inflammation and immunity. Activation of Nrf2 provides broad and long-lasting cytoprotection, and is often hijacked by cancer cells, allowing their survival under unfavorable conditions. Moreover, Nrf2 activation in established human tumors is associated with resistance to chemo-, radio-, and immunotherapies. In addition to cancer cells, Nrf2 activation can also occur in tumor-associated macrophages (TAMs) and facilitate an anti-inflammatory, immunosuppressive tumor immune microenvironment (TIME). Several cancer cell-derived metabolites, such as itaconate, L-kynurenine, lactic acid and hyaluronic acid, play an important role in modulating the TIME and tumor-TAMs crosstalk, and have been shown to activate Nrf2. The effects of Nrf2 in TIME are context-depended, and involve multiple mechanisms, including suppression of proinflammatory cytokines, increased expression of programmed cell death ligand 1 (PD-L1), macrophage colony-stimulating factor (M-CSF) and kynureninase, accelerated catabolism of cytotoxic labile heme, and facilitating the metabolic adaptation of TAMs. This understanding presents both challenges and opportunities for strategic targeting of Nrf2 in cancer.

Swellable Submicrospheres of Ionic Palladium(II) Complexes Containing Decylmethylbis(m-pyridyl)silane

  • Ryu, Yoon-Kyong;Kim, Cho-Rong;Kim, Chi-Won;Noh, Tae-Hwan;Jung, Ok-Sang
    • Bulletin of the Korean Chemical Society
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    • v.30 no.10
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    • pp.2338-2340
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    • 2009
  • Ionic palladium(II) complex containing a long aliphatic chain, [(tmeda)$PdL]_2(PF_6)_4$ (tmeda = N,N,N',N'-tetramethylethylenediamine; L = decylmethylbis(m-pyridyl)silane) allowed to form a puckered submicrosphere morphology without any template or additive. The puckered spheres reversibly adsorb and desorb dioxane molecules. Coligand and cosolvent effects on the formation of submicrospherical morphology were observed.

Synthesis, Structures, and Catalytic Properties of Ionic Metallacyclodimeric Palladium(II) Complexes

  • Kim, Sung Min;Park, Kyung Hwan;Lee, Haeri;Moon, So Yun;Jung, Ok-Sang
    • Bulletin of the Korean Chemical Society
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    • v.33 no.12
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    • pp.4069-4073
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    • 2012
  • Metallacyclodimeric complexes of $[(Me_4en)Pd(L)]_2(ClO_4)_4$ ($Me_4en$ = N,N,N',N'-tetramethylethylenediamine; L = dimethylbis(4-pyridyl)silane (dmps), methylvinylbis(4-pyridyl)silane (mvps)) have been synthesized, and their structures have been characterized by X-ray single crystallography. The skeletal structures consist of one 20-membered metallamacrocycle, two 5-membered metallacycles, and four pyridyl groups. The local geometry around the palladium(II) ion approximates to a typical square planar arrangement with four nitrogen donors. Delicate difference in catalytic effects on hydrogenation was investigated based on the structure of catalyst and substrates.

Hitting the complexity of the TIGIT-CD96-CD112R-CD226 axis for next-generation cancer immunotherapy

  • Jin, Hyung-seung;Park, Yoon
    • BMB Reports
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    • v.54 no.1
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    • pp.2-11
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    • 2021
  • Antibody-based therapeutics targeting the inhibitory receptors PD-1, PD-L1, or CTLA-4 have shown remarkable clinical progress on several cancers. However, most patients do not benefit from these therapies. Thus, many efforts are being made to identify new immune checkpoint receptor-ligand pathways that are alternative targets for cancer immunotherapies. Nectin and nectin-like molecules are widely expressed on several types of tumor cells and play regulatory roles in T- and NK-cell functions. TIGIT, CD226, CD96 and CD112R on lymphoid cells are a group of immunoglobulin superfamily receptors that interact with Nectin and nectin-like molecules with different affinities. These receptors transmit activating or inhibitory signals upon binding their cognate ligands to the immune cells. The integrated signals formed by their complex interactions contribute to regulating immune-cell functions. Several clinical trials are currently evaluating the efficacy of anti-TIGIT and anti-CD112R blockades for treating patients with solid tumors. However, many questions still need to be answered in order to fully understand the dynamics and functions of these receptor networks. This review addresses the rationale behind targeting TIGIT, CD226, CD96, and CD112R to regulate T- and NK-cell functions and discusses their potential application in cancer immunotherapy.

A Case of Pseudodeficiency in a Potential Late Onset Pompe Disease Carrier, with Double Dual Variant, Each in cis Formation (Pseudodeficiency 및 potential late onset Pompe disease 보인자로 확인된 cis형 dual variant 돌연변이 두 개를 가진 여아 1례)

  • Seung Ho, Kim;Goo Lyeon, Kim;Young Pyo, Chang;Dong Hwan, Lee
    • Journal of The Korean Society of Inherited Metabolic disease
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    • v.22 no.2
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    • pp.58-62
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    • 2022
  • Pompe disease (PD) is an autosomal recessive genetic disorder caused by a deficiency of the lysosomal enzyme acid α-glucosidase (GAA). It is easy to hastily diagnose as patients if they have two pathogenic variants. Clinical pathologists misdiagnosed our infant and her mother as PD. Here, we report a case of pseudodeficiency in a potential late-onset Pompe disease (LOPD) carrier with a double dual variant, each in cis formation in a 3-month infant. The person who has two pathogenic variants was diagnosed as a carrier, not a patient. It was first reported in Korea. The patient had: two likely pathogenic heterozygous mutations on exon #4: c.752C>T (p.Ser251Leu), c.761C>T (p.Ser254Leu), and a heterozygous mutation on exon #12: c.1726G>A (p.Gly576Ser), also with a heterozygous mutation on exon #15: c.2065G>A (p.Glu689Lys). By presenting this case we emphasize the possibility of cis formation of genes which may cause pseudodeficiency, and potential LOPD carrier form. Hereby we suggest that thorough evaluation of GAA gene is essential among whom initially diagnosed as PD.

The Antioxidant Effect of Vitamin C and Deferoxamine on Paraquat-induced Cytotoxicity in Cultured Lymphocytes (배양림프구에서 Paraquat의 세포독성에 대한 Vitamin C와 Deferoxamine의 항산화 효과)

  • Eo Eun-Kyung;Kim Kyung-Hee
    • Journal of The Korean Society of Clinical Toxicology
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    • v.4 no.1
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    • pp.7-16
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    • 2006
  • Purpose: As basic information of antioxidant treatments for the patient with paraquat intoxication, in human peripheral lymphocytes, the cytotoxicity of paraquat was measured, and to evaluate the antioxidant effect of vitamin C and deferoxamine against this cytotoxicity, malondialdehyde (MDA), superoxide dismutase (SOD) activity and total antioxidant status (TAS) were measured. Methods: From 10 healthy adults, after obtaining a consent, 20ml peripheral blood was collected. Experimental groups were divided to (1) control group, the group treated with an identical amount of saline, (2) P group: the group treated with paraquat only, (3) PV group: the group treated with paraquat followed by vitamin C 30 minutes later, (4) PD group: the group treated with paraquat followed by deferoxamine 30 minutes later, (5) PVD group: the group treated with paraquat followed by vitamin C 30 minutes later and subsequently deferoxamine one hour later, and (6) PDV group: the group treated with paraquat followed by deferoxamine 30 minutes later and subsequently vitamin C 1 hour later, and thus to total 6 groups. In each group, 10 samples of peripheral blood was assigned and $100{\mu}M\;paraquat,\;100{\mu}M$ vitamin C, and $100{\mu}M$ deferoxamine were used as reagent. Lymphocytes were isolated, cultured, and cytotoxicity was measured by the Microculture Tetrazolium method (MTT assay), MDA and SOD activity, and TAS concentration were measured. Results: In regard to the cytotoxicity measured in each group, their cytotoxicity was decreased in the group treated with antioxidants, in comparison with the group treated with paraquat only. In the cases that the order of the treatment of these two antioxidants was altered, viability in the PDV group $(1.077{\pm}0.121)$ was increased more that the PVD group $(0.888{\pm}0.152)$ statistically significantly (p=0.018). Concerning the amount of MDA, in comparison with the P group $(6.78{\pm}0.93{\mu}mol/L)$, after the treatment of each antioxidant, the concentration of MDA was decreased statistically significantly (p<0.05). In the group treated with two antioxidants together, in comparison with the group treated only with one antioxidant, the amount of MDA was increased statistically significantly $(PV:\;3.96{\pm}0.98{\mu}mol/L,\;PD:\;4.92{\pm}1.50{\mu}mol/L,\;PVD:\;3.22{\pm}0.83{\mu}mol/L,\;and\;PDV:\;3.42{\pm}0.95{\mu}mol/L,\;p=0.007)$. The concentration of SOD measured in the blood in each group after the administration of paraquat, in comparison with the control group, a pattern of the elevation of SOD activity and subsequent decrease was detected, however, it was not statistically significant. In the comparison of the groups treated with antioxidants, in comparison with the P group $(1419.9{\pm}265.9{\mu}mol/L)$, SOD activity was decreased statistically significantly in only the PDV group $(1176.4{\pm}238.9{\mu}mol/L)$ (p=0.017). In regard to TAS measured in each group, in comparison with the P group $(0.87{\pm}0.05{\mu}mol/L)$, in all groups treated with the antioxidants, the PV group was $1.00{\pm}0.03{\mu}mol/L$ (p=0.005), the PD group was $9.01{\pm}0.24{\mu}mol/L$ was $4.64{\pm}3.98{\mu}mol/L$ (P=0.005), and the PDV group was $9.41{\pm}0.27{\mu}mol/La$ (p=0.005), and thus total antioxidant activity was increased statistically significantly In a multiple comparison test, the PDV group showed the highest total antioxidant activity (p<0.0001). Conclusion: The result of the assessment of the antioxidant effect of vitamin C and deferoxamine on paraquat-induced cytotoxicity showed that in regard to cytotoxicity, SOD activity and TAS measurement, the best result was observed in the PDV group. Therefore, it was found that vitamin C and deferoxamine were effective antioxidants for the paraquat-induced cytotoxicity, and it suggests that the administration of deferoxamine followed by vitamin C may improve their antioxidant effect more.

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The Anti-Proliferation and Oxidative Damage-Related Mechanism of L-Carnitine in Human Colorectal Cancer Cells (L-carnitine에 의한 인간대장암세포주 증식억제 및 산화적손상 기전 규명)

  • Lee, Jooyeon;Park, Jeong-Ran;Jang, Aera;Yang, Se-Ran
    • Journal of Food Hygiene and Safety
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    • v.34 no.3
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    • pp.303-308
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    • 2019
  • L-carnitine is found in high levels in muscle tissues. It has been developed as a nutrient and dietary supplement, and also used as a therapeutic supplement in various diseases including type II diabetes, osteoporosis and metabolic neuropathies. However, it is not fully understood how it affects cellular mechanisms in colorectal cancer. Therefore, we attempted to determine the effect of L-carnitine in HCT116 human colorectal cancer cells. First, the HCT116 cells were exposed to L-carnitine for 24 hours at 0-40 mM, and then analyzed for cellular proliferation, oxidative stress and related mechanisms. In a MTT assay, L-carnitine inhibited cellular proliferation and induced reactive oxygen species (ROS) in HCT116 by DCF-DA analysis. To analyze the mechanism of L-carnitine in colorectal cancer cells, we performed a western blot analysis for pERK1/2 and pp38 MAP kinase. The western blot showed that L-carnitine significantly increased protein levels of pERK1/2 and pp38 compared with control. Taken together, we found that L-carnitine has anti-proliferative function via increased ROS and activation of ERK1/2 and p38 pathway in HCT116. These findings suggest that L-carnitine may have an anti-proliferative role on colorectal cancer.

Process Suggestion and HAZOP Analysis for CQ4 and Q2O in Nuclear Fusion Exhaust Gas (핵융합 배가스 중 CQ4와 Q2O 처리공정 제안 및 HAZOP 분석)

  • Jung, Woo-Chan;Jung, Pil-Kap;Kim, Joung-Won;Moon, Hung-Man;Chang, Min-Ho;Yun, Sei-Hun;Woo, In-Sung
    • Korean Chemical Engineering Research
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    • v.56 no.2
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    • pp.169-175
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    • 2018
  • This study deals with a process for the recovery of hydrogen isotopes from methane ($CQ_4$) and water ($Q_2O$) containing tritium in the nuclear fusion exhaust gas (Q is Hydrogen, Deuterium, Tritium). Steam Methane Reforming and Water Gas Shift reactions are used to convert $CQ_4$ and $Q_2O$ to $Q_2$ and the produced $Q_2$ is recovered by the subsequent Pd membrane. In this study, one circulation loop consisting of catalytic reactor, Pd membrane, and circulation pump was applied to recover H components from $CH_4$ and $H_2O$, one of $CQ_4$ and $Q_2O$. The conversion of $CH_4$ and $H_2O$ was measured by varying the catalytic reaction temperature and the circulating flow rate. $CH_4$ conversion was 99% or more at the catalytic reaction temperature of $650^{\circ}C$ and the circulating flow rate of 2.0 L/min. $H_2O$ conversion was 96% or more at the catalytic reaction temperature of $375^{\circ}C$ and the circulating flow rate of 1.8 L/min. In addition, the amount of $CQ_4$ generated by Korean Demonstration Fusion Power Plant (K-DEMO) in the future was predicted. Then, the treatment process for the $CQ_4$ was proposed and HAZOP (hazard and operability) analysis was conducted to identify the risk factors and operation problems of the process.

Immuno-Activities of Extracts of Tofu Fermented with Pleurotus eryngii Mycelia (큰느타리버섯 균사체로 제조한 발효두부 추출물의 면역 활성)

  • Lee, Sang-Won;Kang, Jong-Woo;Kim, Jae-Yong;Park, Kyung-Wuk;Park, Seok-Kyu;Joo, Ok-Soo;Yee, Sung-Tae;Seo, Kwon-Il
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.39 no.1
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    • pp.25-30
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    • 2010
  • In order to improve the functional benefits and storage properties of soybean tofu, fermented tofu was developed using Pleurotus eryngii mycelia. The immune activities of water and methanol extracts of the tofu were investigated. The optimal medium for the growth of Pleurotus eryngii mycelia was PD broth medium and the optimal fermentation period for the tofu was 7 days. The water and methanol extracts of the fermented tofu induced the proliferation of spleen cells at above $0.01 {\mu}g/mL$. The water extract increased IL-2, IFN-$\gamma$ production, while the methanol extract increased IFN-$\gamma$ synthesis. The water and methanol extracts of the fermented tofu induced the NO production in RAW264.7 macrophage cells at above $1 {\mu}g/mL$ and above $10 {\mu}g/mL$ concentration, respectively. The extracts also significantly increased the production of IL-6, TNF-$\alpha$, IL-1$\beta$ and GM-CSF in the cells. These results suggest that the tofu fermented with Pleurotus eryngii mycelia could be developed as a functional tofu.

Reconvery of Platinum Group Metals from Spent Automotive Catalysts by Hydrochloric Acid Leaching (自動車 廢觸媒로부터 鹽酸浸出에 의한 自金族 金屬의 回收)

  • Lee, Jae-Chun;Jeong, Jin-Ki;Kim, Min-Seuk;Kim, Byung-Su;Kim, Chi-Kwon
    • Resources Recycling
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    • v.13 no.5
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    • pp.28-36
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    • 2004
  • The extraction of platinum group metals such as Pt, Pd and Rh from spent automobile catalyst has been investigated by leaching in HCl solutions using $HNO_3$ or NaOCl as a oxidant. The effect of type and amount of oxidant, reaction time and pulp density on the extraction of platinum group metals was examined. Platinum group metals were recovered by the cementation method using aluminum as a reducing agent. The extraction ratio was higher when NaOCl was used as a oxidant. The optimum leaching conditions were obtained to be: HCl 8 M, the amount of NaOCl 1.4 mole, leaching temperature $90^{\circ}C$, leaching time 180 minutes, pulp density 400g/L. Under the optimum conditions, the extraction of Pt, Pd and Rh were 96.1%, 93.6% and 77.3%, respectively. With the addition of 2.0g of aluminum which corresponds to 28 equivalent the reduction were 98% for Pt. 98.8% for Pd and 65.3% for Rh, respectively.