MiR-144-3p and Its Target Gene beta-Amyloid Precursor Protein Regulate 1-Methyl-4-Phenyl-1,2-3,6-Tetrahydropyridine-Induced Mitochondrial Dysfunction

Lixuan Wang,Kuo Li,Junling Zhang,Chunxue Ji 한국분자세포생물학회 2016 Molecules and cells Vol.39 No.7

MicroRNAs (miRNAs) have been reported to be involved in many neurodegenerative diseases. The present study focused on the role of hsa-miR-144-3p in one of the neurodegenerative diseases, Parkinson’s disease (PD). Our study showed a remarkable down-regulation of miR-144-3p expression in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-treated SH-SY5Y cells. MiR-144-3p was then overexpressed and silenced in human SH-SY5Y cells by miRNA-mimics and miRNA-inhibitor transfections, respectively. Furthermore, -amyloid precursor protein (APP) was identified as a target gene of miR-144-3p via a luciferase reporter assay. We found that miR-144-3p overexpression significantly inhibited the protein expression of APP. Since mitochondrial dysfunction has been shown to be one of the major pathological events in PD, we also focused on the role of miR-144-3p and APP in regulating mitochondrial functions. Our study demonstrated that up-regulation of miR-144-3p increased expression of the key genes in-volved in maintaining mitochondrial function, including peroxisome proliferator-activated receptor γ coactivator-1 (PGC-1), nuclear respiratory factor 1 (NRF-1) and mitochondrial transcription factor A (TFAM). Moreover, there was also a significant increase in cellular ATP, cell viability and the relative copy number of mtDNA in the presence of miR-144-3p overexpression. In contrast, miR-144-3p silencing showed opposite effects. We also found that APP overexpression significantly decreased ATP level, cell viability, the relative copy number of mtDNA and the expression of these three genes, which reversed the effects of miR-144-3p overexpression. Taken together, these results show that miR-144-3p plays an important role in maintaining mitochondrial function, and its target gene APP is also involved in this process.

Genome-wide association study of gastric adenocarcinoma in Asia: a comparison of associations between cardia and non-cardia tumours

Hu, Nan,Wang, Zhaoming,Song, Xin,Wei, Lixuan,Kim, Byung Sik,Freedman, Neal D,Baek, Jiwon,Burdette, Laurie,Chang, Jiang,Chung, Charles,Dawsey, Sanford M,Ding, Ti,Gao, Yu-Tang,Giffen, Carol,Han, Yaling British Medical Association 2016 Gut Vol.65 No.10

<P>Objective Genome-wide association studies (GWAS) of gastric cancer have reported differences in single-nucleotide polymorphism (SNP) associations for tumour subtypes, particularly when divided by location into the gastric cardia versus the non-cardia. Design Here we present results for a GWAS using 2350 East Asian gastric cancer cases divided as 1189 gastric cardia and 1027 gastric non-cardia cases and 2708 controls. We also included up to 3042 cardia cases, 4359 non-cardia cases and 7548 controls for replication from two Chinese studies and one Korean study. From the GWAS, we selected 12 top SNPs for each gastric cancer subtype, 4 top SNPs for total gastric cancer and 1 SNP in MUC1 for replication testing. Results We observed genome-wide significant associations for rs10074991 in PRKAA1 at 5p13.1 for cardia (p=7.36x10(-12)) and non-cardia cancers (p=2.42x10(-23)) with per allele OR (95% CI) for the combined endpoint of 0.80 (0.77 to 0.83). At 6p21.1, rs2294693 near UNC5CL was significantly associated with gastric non-cardia cancer risk (p=2.50x10(-8)), with OR (95% CI) of 1.18 (1.12 to 1.26), but there was only a nominal association for cardia cancer (p=1.47x10(-2)). We also confirmed a previously reported association for rs4072037 in MUC1 with p=6.59x10(-8) for total gastric cancer and similar estimates for cardia and non-cardia cancers. Three SNPs in PSCA previously reported to be associated with gastric non-cardia cancer showed no apparent association for cardia cancer. Conclusions Our results suggest that associations for SNPs with gastric cancer show some different results by tumour location in the stomach.</P>

Experimental study on the gas jet characteristics of a diesel-piloted direct-injection natural gas engine

Peng Jiang,Xu Liu,Lixuan Cao,Qian Wang,Zhixia He 대한기계학회 2021 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.35 No.3

The natural gas (NG) jet characteristics of NG/diesel dual-fuel injection under different NG injection pressures and dual-fuel injection intervals were studied in a constant volume chamber. The schlieren images showed that the development of NG jet was restricted in both axial and radial directions by diesel spray under dual-fuel injection conditions. Consistently, dual-fuel injection reduced NG jet tip penetration, NG jet cone angle and NG jet volume, yet increased average fuel-air equivalent ratio, compared to NG single-fuel injection. The increase of NG injection pressure from 3 MPa to 5 MPa enhanced NG jet tip penetration and NG jet volume, yet decreased jet cone angle under both single-fuel and dual-fuel injection conditions. The negative effects of diesel spray on NG jet became gradually reduced with the increase of injection interval. When the injection interval was longer than 1.5 ms, NG jet characteristics were close to those under single-fuel conditions.

Numerical investigation of dual-fuel direct injection on RCCI combustion performance at low load condition

Peng Jiang,Xu Liu,Lixuan Cao,Qian Wang,Zhixia He 대한기계학회 2021 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.35 No.9

A numerical study was performed to investigate the combustion characteristics of hydrogenated catalytic biodiesel (HCB)/gasoline reactivity controlled compression ignition (RCCI) with dual-fuel direct injection at low load condition. The results indicated that compared with the conventional port injection RCCI, the dual-fuel direct injection can effectively control the distribution of in-cylinder gasoline mixture and improve the incomplete combustion phenomenon. The delay of start of injection (SOI) of gasoline can weaken stratified combustion, shorten combustion duration, reduce combustion efficiency, decrease NOx emission and increase soot emission. In contrast, the delay of SOI of HCB can intensify stratified combustion, prolong combustion duration, increase combustion efficiency, increase NOx emission and reduce soot emission. Compared with gasoline injection timing, HCB injection timing has a more profound effect on combustion efficiency and indicated thermal efficiency. When HCB injection timing was in the range of -25° ATDC (after top dead center) to -20° ATDC and gasoline injection timing of -50° ATDC to -45°ATDC, the engine has a better performance, with the combustion efficiency about 94 %, the indicated thermal efficiency around 45 %, and the NOx and soot emissions in the original exhaust less than the limit value of Euro VI standard.

MiR-144-3p and Its Target Gene β-Amyloid Precursor Protein Regulate 1-Methyl-4-Phenyl-1,2-3,6-Tetrahydropyridine-Induced Mitochondrial Dysfunction

Li, Kuo,Zhang, Junling,Ji, Chunxue,Wang, Lixuan Korean Society for Molecular and Cellular Biology 2016 Molecules and cells Vol.39 No.7

MicroRNAs (miRNAs) have been reported to be involved in many neurodegenerative diseases. The present study focused on the role of hsa-miR-144-3p in one of the neuro-degenerative diseases, Parkinson's disease (PD). Our study showed a remarkable down-regulation of miR-144-3p expression in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-treated SH-SY5Y cells. MiR-144-3p was then overexpressed and silenced in human SH-SY5Y cells by miRNA-mimics and miRNA-inhibitor transfections, respectively. Furthermore, ${\beta}$-amyloid precursor protein (APP) was identified as a target gene of miR-144-3p via a luciferase reporter assay. We found that miR-144-3p overexpression significantly inhibited the protein expression of APP. Since mitochondrial dysfunction has been shown to be one of the major pathological events in PD, we also focused on the role of miR-144-3p and APP in regulating mitochondrial functions. Our study demonstrated that up-regulation of miR-144-3p increased expression of the key genes involved in maintaining mitochondrial function, including peroxisome proliferator-activated receptor ${\gamma}$ coactivator-$1{\alpha}$(PGC-$1{\alpha}$), nuclear respiratory factor 1 (NRF-1) and mitochondrial transcription factor A (TFAM). Moreover, there was also a significant increase in cellular ATP, cell viability and the relative copy number of mtDNA in the presence of miR-144-3p overexpression. In contrast, miR-144-3p silencing showed opposite effects. We also found that APP overexpression significantly decreased ATP level, cell viability, the relative copy number of mtDNA and the expression of these three genes, which reversed the effects of miR-144-3p overexpression. Taken together, these results show that miR-144-3p plays an important role in maintaining mitochondrial function, and its target gene APP is also involved in this process.