BCR/ABL mRNA Targeting Small Interfering RNA Effects on Proliferation and Apoptosis in Chronic Myeloid Leukemia

Zhu, Xi-Shan,Lin, Zi-Ying,Du, Jing,Cao, Guang-Xin,Liu, Gang Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.12

Background: To investigate the effects of small interference RNA (siRNA) targeting BCR/ABL mRNA on proliferation and apoptosis in the K562 human chronic myeloid leukemia (CML) cell line and to provide a theoretical rationale and experimental evidence for its potential clinical application for anti-CML treatment. Materials and Methods: The gene sequence for BCR/ABL mRNA was found from the GeneBank. The target gene site on the BCR/ABL mRNA were selected according to Max-Planck-Institute (MPI) and rational siRNA design rules, the secondary structure of the candidate targeted mRNA was predicted, the relevant thermodynamic parameters were analyzed, and the targeted gene sequences were compared with BLAST to eliminate any sequences with significant homology. Inhibition of proliferation was evaluated by MTT assay and colony-formation inhibiting test. Apoptosis was determined by flow cytometry (FCM) and the morphology of apoptotic cells was identified by Giemsa-Wright staining. Western blotting was used to analyze the expression of BCR/ABL fusion protein in K562 cells after siRNA treatment. Results: The mRNA local secondary structure calculated by RNA structure software, and the optimal design of specific siRNA were contributed by bioinformatics rules. Five sequences of BCR/ABL siRNAs were designed and synthesized in vitro. Three sequences, siRNA1384, siRNA1276 and siRNA1786, which showed the most effective inhibition of K562 cell growth, were identified among the five candidate siRNAs, with a cell proliferative inhibitory rate nearly 50% after exposure to 12.5nmol/L~50nmol/L siRNA1384 for 24,48 and 72 hours. The 50% inhibitory concentrations ($IC_{50}$) of siRNA1384, siRNA1276 and siRNA1786 for 24hours were 46.6 nmol/L, 59.3 nmol/L and 62.6 nmol/L, respectively, and 65.668 nmol/L, 76.6 nmol/L, 74.4 nmol/L for 72 hours. The colony-formation inhibiting test also indicated that, compared with control, cell growth of siRNA treated group was inhibited. FCM results showed that the rate of cell apoptosis increased 24 hours after transfecting siRNA. The results of annexinV/PI staining indicated that the rate of apoptosis imcreased (1.53%, 15.3%, 64.5%, 57.5% and 21.5%) following treamtne with siRNAs (siRNA34, siRNA372, siRNA1384, siRNA1276 and siRNA1786). Morphological analysis showed td typical morphologic changes of apoptosis such as shrunken, fragmentation nucleus as well as "apoptotic bodies" after K562 cell exposure to siRNA. Western blot analysis showed that BCR/ABL protein was reduced sharply after a single dose of 50nmol/L siRNA transfection. Conclusions: Proliferation of K562 cells was remarkbly inhibited by siRNAs (siRNA1384, siRNA1276 and siRNA1786) in a concentration-dependent manner in vitro, with effective induction of apoptosis at a concentration of 50 nmol/L. One anti-leukemia mechanism in K562 cells appeared that BCR/ABL targeted protein was highly down-regulated. The siRNAs (siRNA1384, siRNA1276 and siRNA1786) may prove valuable in the treatment of CML.

No Association between Traffic Density and Risk of Childhood Leukemia: a Meta-analysis

Sun, Xiao-Xi,Zhang, Shan-Shan,Ma, Xiao-Ling Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.13

Background: While many studies have concluded that local traffic density is positively associated with childhood leukemia, the results are inconsistent. We therefore performed a meta-analysis to assess the relationship between traffic density and the risk of childhood leukemia. Methods: A systematic literature review was carried out using PubMed, EMBASE, and the Cochrane Library from January 1979 to December 2013. We selected and assessed journal articles evaluating the relationship between local traffic density and the risk of leukemia in children. The analysis was carried out using STATA version 12.0. Results: A total of 11 articles, including 12 estimates of effect, were included in our meta-analysis. The summary effect size from the random-effects model, expressed as an odds ratio, was 1.03 (95% CI: 0.98-1.09, p=0.002). No significant association between traffic density and the risk of childhood leukemia was found. Similar conclusions were found on subgroup analysis. Conclusions: The results of our meta-analysis suggested no association between traffic density and the risk of childhood leukemia. This implies that living in close proximity to roads with heavy traffic may not increase the risk of childhood leukemia. However, further high-quality prospective trials are needed to support these results.

The SH2 domain is crucial for function of Fyn in neuronal migration and cortical lamination

( Xi Lu ),( Xin De Hu ),( Ling Zhen Song ),( Lei An ),( Ming Hui Duan ),( Shu Lin Chen ),( Shan Ting Zhao ) 생화학분자생물학회(구 한국생화학분자생물학회) 2015 BMB Reports Vol.48 No.2

Neurons in the developing brain form the cortical plate (CP) in an inside-out manner, in which the late-born neurons are located more superficially than the early-born neurons. Fyn, a member of the Src family kinases, plays an important role in neuronal migration by binding to many substrates. However, the role of the Src-homology 2 (SH2) domain in function of Fyn in neuronal migration remains poorly understood. Here, we demonstrate that the SH2 domain is essential for the action of Fyn in neuronal migration and cortical lamination. A point mutation in the Fyn SH2 domain (FynR176A) impaired neuronal migration and their final location in the cerebral cortex, by inducing neuronal aggregation and branching. Thus, we provide the first evidence of the Fyn SH2 domain contributing to neuronal migration and neuronal morphogenesis. [BMB Reports 2015; 48(2): 97-102]

Sensitivity of Plasmodium falciparum to Antimalarial Drugs in Hainan Island, China

Shan-Qing Wang,Guang-Ze Wang,Yu-Chun Li,Feng Meng,Shi-Gan Lin,Zhen-Hu Zhu,Ding-Wei Sun,Chang-Hua He,Xi-Min Hu,Jian-Wei Du 대한기생충학열대의학회 2015 The Korean Journal of Parasitology Vol.53 No.1

Effect of Germination and Heating on Phytase Activity in Cereal Seeds

Ma, Xi,Shan, Anshan Asian Australasian Association of Animal Productio 2002 Animal Bioscience Vol.15 No.7

The effect of germination on phytase activity in wheat NEAU123, triticale5305 and rye2 was studied in the present study. Germination significantly increased phytase activity by 2.04 times for wheat NEAU123 (3 d), 1.82 times for triticale 5305 (1 d) and 2.45 times for rye2 (1 d), respectively. It was safe for phytase in fresh malts kilned for 2 h at $40^{\circ}C$. Phytase in cereal seeds had strong heat stability. There was no loss of phytase activity in cereal seeds heated at $70^{\circ}C$ for 1 h, a little loss (${\leq}$5.46%) at $80^{\circ}C$ or $90^{\circ}C$. Even heated at $100^{\circ}C$, the phytase activity in wheat NEAU123, triticale5305 and rye2 remained 89.47%, 86.44% and 104.64%, respectively.

Synthesis and Anticonvulsant Activity of 1-Formamide-triazolo[4,3- a]quinoline Derivatives

Cheng-Xi Wei,Xian-Qing Deng,채규윤,Zhi-Gang Sun,Zhe-Shan Quan 대한약학회 2010 Archives of Pharmacal Research Vol.33 No.5

Using 6-hydroxy-3,4-dihydro-2(1H)-quinolone as the starting material, a series of 1-formamide-triazolo[4, 3-a]quinoline derivatives (6a-6n) was synthesized, the anticonvulsant effect and neurotoxicity of the compounds was calculated with maximal electroshock test and rotarod tests with intraperitoneally injected in KunMing mice. The results demonstrated that compound 7-(hexyloxy)-4,5-dihydro-[1,2,4] triazolo[4,3-a]quinoline-1-carboxamide (6d) was the most active one and also had the lowest toxicity. In the anti-maximal electroshock potency test, it showed median effective dose (ED50) of 30.1 mg/kg, median toxicity dose (TD50) of 286 mg/kg, and the protective index of 9.5 which is greater than the reference drug carbamazepine with the protective index value of 6.0.

Synthesis of 2-Substituted-6-(4H-1,2,4-triazol-4-yl)benzo[d]oxazoles as Potential Anticonvulsant Agents

Cheng-Xi Wei,Li-Ping Guan,Jing-Hao Jia,채규윤,Zhe-Shan Quan 대한약학회 2009 Archives of Pharmacal Research Vol.32 No.1

A series of 2-substituted-6-(4H-1,2,4-triazol-4-yl)benzo[d]oxazoles were synthesized. The anticonvulsant effect and neurotoxicity of the compounds (intraperitoneally) were evaluated with the maximal electroshock (MES) test, subcutaneous pentylenetetrazole (sc-PTZ), and rotarod tests in mice. 2-Phenyl- 6- (4H-1,2,4-triazol-4-yl)benzo[d]oxazole (3g) was the most active and also had the lowest toxicity. In the anti-MES potency test, it showed median effective dose (ED50) of 29.5 mg/kg, a median toxicity dose (TD50) of 285 mg/kg, and a protective index (PI) of 9.7, which is greater than the reference drug, carbamazepine, which has a PI of 6.4.

Deep Leaky Single-peaked Triangle Neural Networks

Chuan-Hui Shan,Xi-Rong Guo,Jun Ou 제어·로봇·시스템학회 2019 International Journal of Control, Automation, and Vol.17 No.10

Recently, Deep learning has made a great deal of success in processing images, audios, and natural languages and so on. The activation function is one of the key factors in Deep learning. In this paper, according to characteristics of biological neurons, an improved Leaky Single-Peaked Triangle Linear Unit (LSPTLU) activation function is presented for the right-hand response unbounded of Rectified Linear Unit (ReLU) and Leaky ReLU(LReLU). LSPTLU is more in line with the biological neuron essence and achieves the excellent performance of equivalent or beyond ReLU and LReLU on different datsets, e.g., MNIST, Fashion-MNIST, SVHN, IMAGENET, CALTECH101 and CIFAR10 datasets.

Performance of the R-way Colposcopic Evaluation System in Cervical Cancer Screening

Zhao, Jian,Zhang, Xi,Chen, Rui,Zhao, Yu-Qian,Wang, Ting-Ting,He, Shan,Qiao, You-Lin Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.10

Objective: To investigate the diagnostic value of the R-way colposcopic evaluation system (R-way system) in cervical cancer screening. Materials and Methods: Between August 2013 and August 2014, a total of 1,059 cases referred to colposcopy in Peking University First Hospital were studied using both the R-way system and conventional colposcopy. Our study evaluated and compared the diagnostic ability of the two methods in detecting high-grade lesions and cervical cancer (hereinafter called CIN2+). Evaluation indicators including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), Youden index and the area under the curve (AUC) of the receiver operating characteristic (ROC) were calculated. Results: The R-way system had a slightly lower specificity (94.5%) than conventional colposcopy (96.0%) for CIN2+ detection (P=0.181). However, the sensitivity (77.8%) was significantly higher than with the conventional colposcopic method (46.6%) (${\chi}^2=64.351$, P<0.001). In addition, the AUC of the ROC for CIN2+ detection using the R-way system (0.839) was larger than that with conventional colposcopy (0.731) (Z=4.348, P<0.001). If preliminary result had been drawn from cervical exfoliated cytology before colposcopy referral, combination of the R-way system with cytology could increase the sensitivity to 93.9% for CIN2+ detection (excluding ASCUS\LSIL), confirmed by multipoint biopsy or ECC. Conclusions: The diagnostic value of the R-way evaluation system is higher than that of conventional colposcopic evaluation in cervical cancer screening. Moreover, taking the ease of use and standardized quality control management into account, the R-way system is highly preferable.

Cytotoxic Isoflavanones from Uraria clarkei

Xiang-Zhong Huang,Xi-Shan Bai,Hui Liang,Chao Wang,Wen-Juan Li,Junming Guo,Zhi-Yong Jiang 대한화학회 2013 Bulletin of the Korean Chemical Society Vol.34 No.5

Two new isoflavanones, (3R) 5,7,3',4'-tetrahydroxy-2'-methoxyisoflavanone (1) and (3R) 5',8-di-(γ,γ- dimethylallyl)-2',5-dihydroxyl-4',7-dimethoxyl-isoflavanone (2), were isolated from Uraria clarkei, together with two known compounds dalbergioidin (3), 5,7-dihydroxy-2',4'-dimethoxyisoflavanone (4). The structures involving the absolute configuration of the new compounds were well elucidated by MS, IR, UV, CD, 1D and 2D NMR analyses. Cytotoxicity of the four compounds were assessed, results suggested that compound 2 possessed well cytotoxic activity, against the Hela, K562, and HL60 cell lines with IC50 values of 28.0, 40.6 and 35.1 μM, respectively.