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TRPV1 on astrocytes rescues nigral dopamine neurons in Parkinson’s disease via CNTF
Nam, Jin H.,Park, Eun S.,Won, So-Yoon,Lee, Yu A.,Kim, Kyoung I.,Jeong, Jae Y.,Baek, Jeong Y.,Cho, Eun J.,Jin, Minyoung,Chung, Young C.,Lee, Byoung D.,Kim, Sung Hyun,Kim, Eung-Gook,Byun, Kyunghee,Lee, Oxford University Press 2015 Brain Vol.138 No.12
<P>Ciliary neurotrophic factor (CNTF) has a neuroprotective effect on dopaminergic neurons. Nam <I>et al.</I> report that the capsaicin receptor TRPV1 expressed on astrocytes mediates the production of endogenous CNTF to inhibit degeneration of dopaminergic neurons in two rodent models of Parkinson's disease.</P><P> [Figure] </P><P>Currently there is no neuroprotective or neurorestorative therapy for Parkinson’s disease. Here we report that transient receptor potential vanilloid 1 (TRPV1) on astrocytes mediates endogenous production of ciliary neurotrophic factor (CNTF), which prevents the active degeneration of dopamine neurons and leads to behavioural recovery through CNTF receptor alpha (CNTFRα) on nigral dopamine neurons in both the MPP<SUP>+</SUP>-lesioned or adeno-associated virus α-synuclein rat models of Parkinson’s disease. Western blot and immunohistochemical analysis of human post-mortem substantia nigra from Parkinson’s disease suggests that this endogenous neuroprotective system (TRPV1 and CNTF on astrocytes, and CNTFRα on dopamine neurons) might have relevance to human Parkinson’s disease. Our results suggest that activation of astrocytic TRPV1 activates endogenous neuroprotective machinery <I>in vivo</I> and that it is a novel therapeutic target for the treatment of Parkinson’s disease.</P>
RODIUM - CATALYZED CARBONYLATION OF METHYL GLYCOLATE AND GLYCOLIC ACID
Lee, Jae S,Lee, Sang Ho,Kim, Eung Jo,Park, Kwang Ho 한국화학공학회 1991 Korean Journal of Chemical Engineering Vol.8 No.1
Catalytic carbonylation of methyl glycolate in the presence of a homogeneous Rh complex and an iodide promoter yields acetoxy methyl acetate and acetic acid. Carbonylation of glycolic acid under the same conditions gives acetic acid and CO₂, probably from decomposition of the malonic acid intermediate.
TSC2 genetic variant and prognosis in non‐small cell lung cancer after curative surgery
Lee, Yong Hoon,Do, Sook Kyung,Lee, Shin Yup,Kang, Hyo‐,Gyoung,Choi, Jin Eun,Hong, Mi Jeong,Lee, Jang Hyuck,Lee, Eung Bae,Jeong, Ji Yun,Shin, Kyung Min,Lee, Won Kee,Seok, Yangki,Cho, Sukki,Yoo, S Wiley-Blackwells 2019 Thoracic Cancer Vol.10 No.2
<P>This study was conducted to investigate the associations between polymorphisms of genes involved in the LKB1 pathway and the prognosis of patients with non‐small cell lung cancer (NSCLC) after surgical resection. Twenty‐three single nucleotide polymorphisms (SNPs) in the LKB1 pathway were investigated in 782 patients with NSCLC who underwent curative surgery. The association of SNPs with overall survival (OS) and disease‐free survival (DFS) were analyzed. Among the 23 SNPs investigated, <I>TSC2</I> rs30259G > A was associated with significantly worse OS and DFS (adjusted hazard ratio for OS 1.88, 95% confidence interval 1.21–2.91, <I>P</I> = 0.005; adjusted hazard ratio for DFS 1.65, 95% confidence interval 1.15–2.38, <I>P</I> = 0.01, under codominant models, respectively). Subgroup analysis showed that SNPs were significantly associated with survival outcomes in squamous cell carcinoma, ever‐smokers, and stage I, but not in adenocarcinoma, never‐smokers, and stage II–IIIA. The results suggest that <I>TSC2</I> rs30259G > A may be useful to predict prognosis in patients with NSCLC, especially squamous cell carcinoma, after curative surgery.</P>
Hong, Mi Jeong,Yoo, Seung Soo,Choi, Jin Eun,Kang, Hyo‐,Gyoung,Do, Sook Kyung,Lee, Jang Hyuck,Lee, Won Kee,Lee, Jaehee,Lee, Shin Yup,Cha, Seung Ick,Kim, Chang Ho,Lee, Eung Bae,Cho, Sukki,Jheon, S John Wiley and Sons Inc. 2018 Cancer Science Vol.109 No.12
<P>RegulomeDB is a new tool that can predict the regulatory function of genetic variants. We applied RegulomeDB in selecting putative functional variants and evaluated the relationship between these variants and survival outcomes of surgically resected non‐small‐cell lung cancer. Among the 244 variants studied, 14 were associated with overall survival (<I>P </I><<I> </I>0.05) in the discovery cohort and one variant (rs2257609 C>T) was replicated in the validation cohort. In the combined analysis, rs2257609 C>T was significantly associated with worse overall and disease‐free survival under a dominant model (<I>P </I>=<I> </I>2 × 10<SUP>−5</SUP> and <I>P </I>=<I> </I>0.001, respectively). rs2257609 is located in the <I>SLC5A10</I> intron, but RegulomeDB predicted that this variant affected <I>DRG2</I>, not <I>SLC5A10</I> expression. The expression level of <I>SLC5A10</I> was not different with the rs2257609 genotype. However, <I>DRG2</I> expression was different according to the rs2257609 genotype (<I>P</I><SUB>trend</SUB><SUP> </SUP>= 0.03) and was significantly higher in tumor than in non‐malignant lung tissues (<I>P </I>=<I> </I>1 × 10<SUP>−5</SUP>). Luciferase assay also showed higher promoter activity of <I>DRG2</I> in samples with the rs2257609 T allele (<I>P </I><<I> </I>0.0001). rs2257609 C>T affected <I>DRG2</I> expression and, thus, influenced the prognosis of early‐stage non‐small‐cell lung cancer. This study was approved by the Institutional Review Broad of Kyungpook National University of Hospital (Approval No. KNUMC 2014‐04‐210‐003).</P>