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Infection-specific phosphorylation of glutamyl-prolyl tRNA synthetase induces antiviral immunity
Lee, Eun-Young,Lee, Hyun-Cheol,Kim, Hyun-Kwan,Jang, Song Yee,Park, Seong-Jun,Kim, Yong-Hoon,Kim, Jong Hwan,Hwang, Jungwon,Kim, Jae-Hoon,Kim, Tae-Hwan,Arif, Abul,Kim, Seon-Young,Choi, Young-Ki,Lee, Che NATURE AMERICA INC 2016 NATURE IMMUNOLOGY Vol.17 No.11
<P>The mammalian cytoplasmic multi-tRNA synthetase complex (MSC) is a depot system that regulates non-translational cellular functions. Here we found that the MSC component glutamyl-prolyl-tRNA synthetase (EPRS) switched its function following viral infection and exhibited potent antiviral activity. Infection-specific phosphorylation of EPRS at Ser990 induced its dissociation from the MSC, after which it was guided to the antiviral signaling pathway, where it interacted with PCBP2, a negative regulator of mitochondrial antiviral signaling protein (MAVS) that is critical for antiviral immunity. This interaction blocked PCBP2-mediated ubiquitination of MAVS and ultimately suppressed viral replication. EPRS-haploid (Eprs(+/-)) mice showed enhanced viremia and inflammation and delayed viral clearance. This stimulus-inducible activation of MAVS by EPRS suggests an unexpected role for the MSC as a regulator of immune responses to viral infection.</P>
Mitochondrial reprogramming via ATP5H loss promotes multimodal cancer therapy resistance
Song, Kwon-Ho,Kim, Jae-Hoon,Lee, Young-Ho,Bae, Hyun Cheol,Lee, Hyo-Jung,Woo, Seon Rang,Oh, Se Jin,Lee, Kyung-Mi,Yee, Cassian,Kim, Bo Wook American Society for Clinical Investigation 2018 The Journal of clinical investigation Vol.128 No.9
<P>The host immune system plays a pivotal role in the emergence of tumor cells that are refractory to multiple clinical interventions including immunotherapy, chemotherapy, and radiotherapy. Here, we examined the molecular mechanisms by which the immune system triggers cross-resistance to these interventions. By examining the biological changes in murine and tumor cells subjected to sequential rounds of in vitro or in vivo immune selection via cognate cytotoxic T lymphocytes, we found that multimodality resistance arises through a core metabolic reprogramming pathway instigated by epigenetic loss of the ATP synthase subunit ATP5H, which leads to ROS accumulation and HIF-1 alpha stabilization under normoxia. Furthermore, this pathway confers to tumor cells a stem-like and invasive phenotype. In vivo delivery of antioxidants reverses these phenotypic changes and resensitizes tumor cells to therapy. ATP5H loss in the tumor is strongly linked to failure of therapy, disease progression, and poor survival in patients with cancer. Collectively, our results reveal a mechanism underlying immune-driven multimodality resistance to cancer therapy and demonstrate that rational targeting of mitochondrial metabolic reprogramming in tumor cells may overcome this resistance. We believe these results hold important implications for the clinical management of cancer.</P>
Development of an infant formula certified reference material for the analysis of organic nutrients
Lee, Joonhee,Kim, Byungjoo,Lee, Sun Young,Choi, Jongoh,Kang, Dukjin,Lee, Hwasim,Choi, KiHwan,Lee, Hyeyoung,Sim, Hee-Jung,Baek, Song-Yee,Lee, Honghee,Hyung, Seok-Won,Ahn, Seonghee,Seo, Dongwon,Hwang, J Applied Science Publishers 2019 Food chemistry Vol.298 No.-
<P><B>Abstract</B></P> <P>Infant formula certified reference material (CRM, KRISS CRM 108-02-003) were developed for the analysis of organic nutrients. The CRM is a milk-based infant formula powder, packaged at 14 g per unit. Ten thousand units were prepared and stored at −70 °C. For the certification of each nutrient, ten units were analyzed for simultaneous value-assignment and homogeneity test. Analytical methods used were isotope dilution mass spectrometry (IDMS) based on liquid chromatography mass spectrometer (LC/MS) or gas chromatography mass spectrometer (GC/MS) as higher-order reference methods.13 vitamins, 3 fatty acids, and total cholesterol were certified. The between-unit relative standard deviation of measurement results for each nutrient ranged 0.2% to 2.5%, showing very good homogeneity. The expanded relative uncertainties of the certified values ranged from 1% to 8%, indicating that they have higher-order metrological quality. The values of proximates (proteins, lipids, carbohydrates, water, and ash) were assigned through inter-laboratory comparisons.</P> <P><B>Highlights</B></P> <P> <UL> <LI> An infant formula CRMs for the analysis of organic nutrients was developed. </LI> <LI> Organic nutrients were certified by IDMS approaches as higher-order reference methods. </LI> <LI> Homogeneities and stability of the CRM were evaluated by IDMS approaches. </LI> <LI> Metrological qualities of the certified values were proved by their small uncertainties. </LI> <LI> Five proximates were value-assigned by interlaboratory comparison. </LI> </UL> </P>
Lee, Sang Hoon,Yeo, Yoomi,Kim, Tae-Hyung,Lee, Hong Lyeol,Lee, Jin Hwa,Park, Yong Bum,Park, Jong Sun,Kim, Yee Hyung,Song, Jin Woo,Jhun, Byung Woo,Kim, Hyun Jung,Park, Jinkyeong,Uh, Soo-Taek,Kim, Young The Korean Academy of Tuberculosis and Respiratory 2019 Tuberculosis and Respiratory Diseases Vol.82 No.2
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrosing interstitial pneumonia, which presents with a progressive worsening dyspnea, and thus a poor outcome. The members of the Korean Academy of Tuberculosis and Respiratory Diseases as well as the participating members of the Korea Interstitial Lung Disease Study Group drafted this clinical practice guideline for IPF management. This guideline includes a wide range of topics, including the epidemiology, pathogenesis, risk factors, clinical features, diagnosis, treatment, prognosis, and acute exacerbation of IPF in Korea. Additionally, we suggested the PICO for the use of pirfenidone and nintendanib and for lung transplantation for the treatment of patients with IPF through a systemic literature review using experts' help in conducting a meta-analysis. We recommend this guideline to physicians, other health care professionals, and government personnel in Korea, to facilitate the treatment of patients with IPF.
Song, Bong-Il,Lee, Sang-Woo,Jeong, Shin Young,Chae, Yee Soo,Lee, Won Kee,Ahn, Byeong-Cheol,Lee, Jaetae Society of Nuclear Medicine 2012 The Journal of nuclear medicine Vol.53 No.9
<P>This study assessed the maximum standardized uptake value of metastatic axillary lymph nodes in patients with invasive ductal breast cancer (IDC) to determine the pretreatment prognostic value of (18)F-FDG PET/CT for disease-free survival (DFS).</P>