Polymorphisms in TYMS for Prediction of Capecitabine-Induced Hand-Foot Syndrome in Chinese Patients with Colorectal Cancer

Si-Qi Dong,Tong-Min Wang,Jiang-Bo Zhang,Yong-Qiao He,Wen-Qiong Xue,Zi-Yi Wu,Da-Wei Yang,Lian-Jing Cao,Jing-Wen Huang,Xi-Zhao Li,Pei-Fen Zhang,Xiao-Hui Zheng,Wei-Hua Jia 대한암학회 2021 Cancer Research and Treatment Vol.53 No.3

Purpose Capecitabine is an extensively used oral prodrug of 5-fluorouracil in treatment of colon cancer and is known to cause hand-foot syndrome (HFS). As the target enzyme for capecitabine, thymidylate synthase (TYMS) plays a key role for 5-fluorouracil metabolism and has been associated with some side effects caused by capecitabine. The aim of our study is to identify the possible genetic predictors of capecitabine-induced HFS (CAP-HFS) in Chinese colorectal cancer patients.Materials and Methods Whole exons of TYMS were sequenced for 288 extreme phenotype HFS patients, including 144 severe or early-onset (first 2 cycles) moderate HFS extreme cases and 144 extreme controls with no reported HFS. The associations between polymorphisms and CAP-HFS were analyzed using logistic regression under an additive model.Results We identified a novel risk mutation (c.1A>G, chr18:657743), was associated with severe HFS in an extreme case who was affected during the first cycle of treatment. Moreover, we identified three new variants, rs3786362, rs699517, rs2790, and two previously reported variants, 5’VNTR 2R/3R and 3′-untranslated region 6-bp ins-del, which were significantly associated with CAP-HFS (p < 0.05). In silico analysis revealed that the effect of these polymorphisms in the TYMS region on the development of HFS might not be restricted solely to the regulation of TYMS expression, but also the TYMS catalytic activity through the indirect effect on ENOSF1 expression.Conclusion This study identified new polymorphisms in TYMS gene significantly associated with CAP-HFS, which may serve as useful genetic predictors for CAP-HFS and help to elucidate the underlying mechanism of HFS.

Prevalence and Genetic Characterization of Toxoplasma gondii in House Sparrows (Passer domesticus) in Lanzhou, China

Wei Cong,Si-Yang Huang,Dong-Hui Zhou,Xiao-Xuan Zhang,Nian-Zhang Zhang,Quan Zhao,Xing-Quan Zhu 대한기생충학열대의학회 2013 The Korean Journal of Parasitology Vol.51 No.3

ox-LDL regulates proliferation and apoptosis in VSMCs by controlling the miR-183-5p/FOXO1

Fan Mingqiang,Huang Yinglong,Li Kunsheng,Yang Xiangxiang,Bai Jing,Si Qiaoke,Peng Zhengfei,Jia Chunwen,Zhang Qiangnu,Tao Ding 한국유전학회 2022 Genes & Genomics Vol.44 No.6

Background: microRNA-mRNA axes that are involved in oxidized low-density lipoprotein (ox-LDL)-induced vascular smooth muscle cells (VSMCs) proliferation/apoptosis imbalance need to be further investigated. Objective: To investigate the functional role of miR-183-5p/FOXO1 in VSMCs and its interaction with ox-LDL. Methods: RNA sequencing was used to detect transcriptome changes of VSMCs treated with ox-LDL. miR-183-5p and FOXO1 expression levels in VSMCs after ox-LDL treatment were assessed using qRT-PCR and western blotting. The regulatory effect of miR-183-5p on FOXO1 has been tried to prove using a dual-luciferase reporter assay. The functions of miR-183-5p, and FOXO1 were analyzed by CCK-8 assay and flow cytometry assay. The tissue samples or serum samples of high fat-feeding mice and carotid atherosclerosis patients were collected, and the levels of miR-183-5p/FOXO1 were analyzed. Results: RNA sequencing data showed 81 miRNAs including miR-183-5p was significantly changed after ox-LDL treatment in VSMCs. FOXO1, a miR-183-5p's potential target, was also down-regulated in ox-LDL treated cells. qRT-PCR and western blot found that expression of FOXO1 mRNA and protein significantly reduced in VSMCs treated with ox-LDL, accompanied by overexpression of miR-183-5p. miR-183-5p inhibited FOXO1 mRNA by binding to its 3' UTR. Interference miR-183-5p/FOXO1 could change proliferation/apoptosis imbalance in VSMCs under ox-LDL stimulation. Higher levels of miR-183-5p but reduced FOXO1 can be found in the thoracic aorta tissues of high fat-feeding mice. In serum samples from individuals with carotid atherosclerosis, Higher levels of miR-183-5p were observed. the miR-183-5p level was positively related to the level of serum ox-LDL in patients. Conclusions: Aberrant expression of miR-183-5p/FOXO1 pathway mediated ox-LDL-induced proliferation/apoptosis imbalance in VSMCs. The miR-183-5p/FOXO1 axis can potentially be utilized as the target in the treatment of patients with atherosclerosis.

The impacts of day trading activity on market quality: evidence from the policy change on the Taiwan stock market

( Tun-ya Yang ),( Si-yuan Huang ),( Wei-che Tsai ),( Pei-shih Weng ) 한국파생상품학회(구 한국선물학회) 2020 선물연구 Vol.28 No.4

This paper aims to investigate the impact of day trading on market quality on the Taiwan stock market with the implementation of a unique policy change. This paper examines 396 listed stocks from June 2015 to October 2016, a period when the stock market in Taiwan officially approved selected stocks for day trading for all investors. Within the sample period, the empirical findings show that day trading increases the bid-ask spread, price depth and stock volatility, indicating that day trading activities not only cause higher transaction costs and trading risk but also raise the market’s ability to absorb price impact. This paper considers two-stage regression and tests the exogenous shock because of further relaxation for day trading to deal with the possible endogenous problem and the main findings remain consistent. Since early 2014, the Taiwan stock market has been experiencing a distinct growth in trading volume after unwinding the day trading; however, the results show that the impacts of stock day trading on market quality are not all positive.

Synthesis and Biological Evaluation of 3,6-diaryl-7H-thiazolo[3,2-b] [1,2,4]triazin-7-one Derivatives as Acetylcholinesterase Inhibitors

Zhe Jin,Liu Yang,Si-Jie Liu,Jian Wang,Shuo Li,Huang-Quan Lin,David Chi Cheong Wan,Chun Hu 대한약학회 2010 Archives of Pharmacal Research Vol.33 No.10

Acetylcholinesterase (AChE) inhibitors played an important role in developing a cure for Alzheimer’ s disease. In order to study on the influence of modifications at different groups and side chains on the AChE inhibitory ability and the active sites of 7H-thiazolo[3,2-b][1,2,4]triazin-7-one derivatives, fourteen 3,6-diaryl-7H-thiazolo[3,2-b][1,2,4]triazin-7-one derivatives were designed and synthesized. The study of AChE inhibitory activity was carried out using the Ellman colorimetric assay with huperzine-A as the positive control drug. Most of the target compounds exhibited more than 50% inhibition at 10 μM. Some target compounds showed strong inhibition against AChE. The molecular fields analysis and preliminary structureactivity relationships are discussed.

Design and Positioning Control of a Flexure-Based Nano-positioning Stage Driven by Halbach Array Voice Coil Actuator

Chi Zhang,Xiaolu Huang,Miao Yang,Si-Lu Chen,Jinhua Chen,Guilin Yang 한국정밀공학회 2022 International Journal of Precision Engineering and Vol.23 No.3

A long-stroke nano-positioning stage driven by voice coil actuator (VCA) and supported by flexure guide is designed in this paper. The Halbach permanent magnet array is implemented in the VCA to improve the air-gap flux density with the magnetic concentration effect. The air-gap magnetic fi eld is modeled with an equivalent magnetic structure and verified by finite element analysis. The proposed equivalent magnetic structure reduces the number of boundary condition equations and hence simplifies the analysis procedure. Besides, a novel spring-damping tuning method is proposed based on the equivalent dynamic model of the closed-loop system. This tuning method regards P control and D control as a virtual spring and a virtual damper. The controller parameters are tuned in an intuitive way. Experimental results show that the positioning stage is capable of achieving a resolution of 40 nm within a stroke of 0.8 mm with high repeatability. The spring-damping tuning method ensures better control performance compared to Ziegler Nichols (Z–N) tuning method where overshoot and settling time are decreased.

Meta-analysis of Seven Randomized Control Trials to Assess the Efficacy and Toxicity of Combining EGFR-TKI with Chemotherapy for Patients with Advanced NSCLC who Failed First-Line Treatment

Xiao, Bing-Kun,Yang, Jian-Yun,Dong, Jun-Xing,Ji, Zhao-Shuai,Si, Hai-Yan,Wang, Wei-Lan,Huang, Rong-Qing Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.7

Background: Some recent clinical trials have been conducted to evaluate a combination of EGFR- TKI with chemotherapy for advanced NSCLC patients as second-line therapy, but the results on the efficacy of such trials are inconsistent. The aim of this meta-analysis was to evaluate the efficacy and safety of combination of EGFR-TKI and chemotherapy for patients with advanced NSCLC who failed first-line treatment. Materials and Methods: We searched relative trials from PubMed, EMBASE, ASCO Abstracts, ESMO Abstracts, Cochrane Library and Clinical Trials.gov. Outcomes analyzed were overall response rate (ORR), progression- free survival (PFS), overall survival (OS) and major toxicity. Results: Seven trails eventually were included in this meta-analysis, covering 1,168 patients. The results showed that the combined regimen arm had a significant higher ORR (RR 1.76 [1.16, 2.66], p=0.007) and longer PFS (HR 0.75 [0.66-0.85], p<0.00001), but failed to show effects on OS (HR 0.88 [0.68-1.15], p=0.36). In terms of subgroup results, continuation of EGFR-TKI in addition to chemotherapy after first-line EGFR-TKI resistance confered no improvement in ORR (RR 0.95 [0.68, 1.33], p=0.75) and PFS (HR 0.89[0.69, 1.15], p=0.38), and OS was even shorter (HR1.52 [1.05-2.21], p=0.03). However, combination therapy with EGFR-TKI and chemotherapy after failure of first-line chemotherapy significantly improved the ORR (RR 2.06 [1.42, 2.99], p=0.0002), PFS (HR 0.71 [0.61, 0.82], p<0.00001) and OS (HR 0.74 [0.62-0.88], p=0.0008), clinical benefit being restricted to combining EGFR-TKI with pemetrexed, but not docetaxel. Grade 3-4 toxicity was found at significantly higher incidence in the combined regimen arm. Conclusions: Continuation of EGFR-TKI in addition to chemotherapy after first-line EGFR-TKI resistance should be avoided. Combination therapy of EGFR-TKI and pemetrexed for advanced NSCLC should be further investigated for prognostic and predictive factors to find the group with the highest benefit of the combination strategy.

Genetic Diversity of Toxoplasma gondii Strains from Different Hosts and Geographical Regions by Sequence Analysis of GRA20 Gene

Hong-Rui Ning,Si-Yang Huang,Jin-Lei Wang,Qian-Ming Xu,Xing-Quan Zhu 대한기생충학열대의학회 2015 The Korean Journal of Parasitology Vol.53 No.3

Toxoplasma gondii is a eukaryotic parasite of the phylum Apicomplexa, which infects all warm-blood animals, including humans. In the present study, we examined sequence variation in dense granule 20 (GRA20) genes among T. gondii isolates collected from different hosts and geographical regions worldwide. The complete GRA20 genes were amplified from 16 T. gondii isolates using PCR, sequence were analyzed, and phylogenetic reconstruction was analyzed by maximum parsimony (MP) and maximum likelihood (ML) methods. The results showed that the complete GRA20 gene sequence was 1,586 bp in length among all the isolates used in this study, and the sequence variations in nucleotides were 0-7.9% among all strains. However, removing the type III strains (CTG, VEG), the sequence variations became very low, only 0-0.7%. These results indicated that the GRA20 sequence in type III was more divergence. Phylogenetic analysis of GRA20 sequences using MP and ML methods can differentiate 2 major clonal lineage types (type I and type III) into their respective clusters, indicating the GRA20 gene may represent a novel genetic marker for intraspecific phylogenetic analyses of T. gondii.

C-type natriuretic peptide attenuates renal osteodystrophy through inhibition of FGF-23/MAPK signaling

Dong Dong Zhang,Yang Fang Wu,Wei Xia Chen,Yao Xu,Si Yan Liu,Huang Huang Luo,Guang Mei Jiang,Yue Wu,Peng Hu 생화학분자생물학회 2019 Experimental and molecular medicine Vol.51 No.-

Renal osteodystrophy (ROD) occurs as early as chronic kidney disease (CKD) stage 2 and seems ubiquitous in almost all pediatric patients with CKD stage 5. Fibroblast growth factor (FGF)-23, a bone-derived endocrine regulator of phosphate homeostasis, is overexpressed in CKD and disturbs osteoblast differentiation and matrix mineralization. In contrast, C-type natriuretic peptide (CNP) acts as a potent positive regulator of bone growth. In the present study, we infused CNP into uremic rats and observed whether CNP could attenuate ROD through the inhibition of FGF-23 cascades. In uremic rats, CNP administration significantly alleviated renal dysfunction, calcium phosphate metabolic disorders, hypovitaminosis D, secondary hyperparathyroidism, the decrease in bone turnover markers and retarded bone pathological progression. More importantly, within FGF-23/mitogen-activated protein kinase (MAPK) signaling, the fibroblast growth factor receptor-1, Klotho and alternative (STAT-1/phospho-STAT-1) elements were upregulated by CNP, whereas FGF-23, RAF-1/phospho-RAF-1, and downstream (ERK/phospho-ERK and P38/phospho-P38) elements were paradoxically underexpressed in bone tissue. Therefore, CNP exerts a therapeutic effect on ROD through inhibition of FGF-23/MAPK signaling at the RAF-1 level.

Effects of dietary Enteromorpha powder on reproduction-related hormones and genes during the late laying period of Zi geese

Ma Wei Qing,Zhao Dan Hua,Cheng Huang Zuo,Wang Si Bo,Yang Ji,Hong Xia Cui,Lu Ming Yuan,Wu Hong Zhi,Xu Li,Liu Guo Jun 아세아·태평양축산학회 2021 Animal Bioscience Vol.34 No.3

Objective: The aim of this study was to investigate the effects of Enteromorpha powder supplementation on reproduction-related hormones and genes in the late laying period of Zi geese. Methods: A total of 312 (1-year-old) Zi geese with similar laying rate were randomly divided into 2 groups with 6 replicates each, each with 21 female geese and 5 male geese. The control group was fed with a basal diet and the test group was fed with a diet containing 3% Enteromorpha powder. The trial period lasted for 7 weeks. Results: Our results showed that the laying rate was improved in the test group at each week of trial (p<0.01), and the levels of estradiol in serum and prolactin in ovary were increased compared with the control group (p<0.05). Conclusion: Based on above results, Enteromorpha powder supplementation at 3% could promote reproductive performance during the late laying period of Zi geese. Objective: The aim of this study was to investigate the effects of Enteromorpha powder supplementation on reproduction-related hormones and genes in the late laying period of Zi geese.Methods: A total of 312 (1-year-old) Zi geese with similar laying rate were randomly divided into 2 groups with 6 replicates each, each with 21 female geese and 5 male geese. The control group was fed with a basal diet and the test group was fed with a diet containing 3% <i>Enteromorpha</i> powder. The trial period lasted for 7 weeks.Results: Our results showed that the laying rate was improved in the test group at each week of trial (p<0.01), and the levels of estradiol in serum and prolactin in ovary were increased compared with the control group (p<0.05).Conclusion: Based on above results, <i>Enteromorpha</i> powder supplementation at 3% could promote reproductive performance during the late laying period of Zi geese.