Post-transcriptionla Control in Human Diseases : Chemical genetic dissection of the SMN complex and snRNP biogenesis

( Li Li Wan ),( Mumtaz Kasim ),( Sung Chan Cho ),( Elizebah Ottinger ),( Chi Kong Lau ),( Daniel Battle ),( Jennifer Bachorik ),( Tina Glisovic ),( Cong Li Wang ),( Yoon Cho ),( Gideon Dreyfuss ) 생화학분자생물학회 2008 생화학분자생물학회 춘계학술발표논문집 Vol.2008 No.-

Curdione Inhibits Proliferation of MCF-7 Cells by Inducing Apoptosis

Li, Juan,Bian, Wei-He,Wan, Juan,Zhou, Jing,Lin, Yan,Wang, Ji-Rong,Wang, Zhao-Xia,Shen, Qun,Wang, Ke-Ming Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.22

Background: Curdione, one of the major components of Curcuma zedoaria, has been reported to possess various biological activities. It thus might be a candidate anti-flammatory and cancer chemopreventive agent. However, the precise molecular mechanisms of action of curdione on cancer cells are still unclear. In this study, we investigated the effect of curdione on breast cancer. Materials and Methods: Xenograft nude mice were used to detect the effect of curdione on breast cancer in vivo; we also tested the effect of curdione on breast cancer in vitro by MTT, Flow cytometry, JC-I assay, and western blot. Results: Firstly, we found that curdione significantly suppressed tumor growth in a xenograft nude mouse breast tumor model in a dose-dependent manner. In addition, curdione treatment inhibited cell proliferation and induced cell apoptosis. Moreover, after curdione treatment, increase of impaired mitochondrial membrane potential occurred in a concentration dependent manner. Furthermore, the expression of apoptosis-related proteins including cleaved caspase-3, caspase-9 and Bax was increased in curdione treatment groups, while the expression of the anti-apoptotic Bcl-2 was decreased. Inhibitors of caspase-3 were used to confirm that curdione induced apoptosis. Conclusions: Overall, our observations first suggested that curdione inhibited the proliferation of breast cancer cells by inducing apoptosis. These results might provide some molecular basis for the anti-cancer activity of curdione.

Gene Silencing of β-catenin by RNAi Inhibits Proliferation of Human Esophageal Cancer Cells by Inducing G0/G1 Cell Cycle Arrest

Wang, Jin-Sheng,Ji, Ai-Fang,Wan, Hong-Jun,Lu, Ya-Li,Yang, Jian-Zhou,Ma, Li-Li,Wang, Yong-Jin,Wei, Wu Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.6

Objectives: The aim of the present study was to explore mechanisms underlying the effects of down-regulating ${\beta}$-catenin expression on esophageal carcinoma (EC) cells. Methods: Cell cycle distribution and apoptosis were determined using flow cytometry and annexin V apoptosis assay, respectively. Transmission electron microscopy (TEM) was used to examine changes in ultrastructure, while expression of cyclin D1 protein and mRNA was detected by western blot and real-time PCR. Proliferating cell nuclear antigen (PCNA) and extracellular signal-regulated kinase (ERK) 1-2 were evaluated by Western blot analysis. PCNA labeling index (LI) was determined by immunocytochemistry. Results: Compared with pGen-3-con transfected and Eca-109 cells, the percentage of G0/G1-phase pGen-3-CTNNB1 transfected cells was obviously increased (P<0.05), with no significant difference among the three groups with regard to apoptosis (P>0.05). pGen-3-CTNNB1 transfected cells exhibited obvious decrease in cyclin D1 mRNA and protein expression (P<0.05) and the ultrastructure of Eca-109 cells underwent a significant change after being transfected with pGen-3-CTNNB1, suggesting that down-regulating ${\beta}$-catenin expression can promote the differentiation and maturation. The expression of PCNA and the ERKI/2 phosphorylation state were also down-regulated in pGen-3-CTNNB1 transfected cells (P<0.05). At the same time, the PCNA labeling index was decreased accordingly (P<0.05). Conclusion: Inhibition of EC Eca-109 cellproliferation by down-regulating ${\beta}$-catenin expression could improve cell ultrastructure by mediating blockade in G0/G1 through inhibiting cyclin D1, PCNA and the MAPK pathway (p-ERK1/2).

Mechanistic Analysis of Taxol-induced Multidrug Resistance in an Ovarian Cancer Cell Line

Wang, Ning-Ning,Zhao, Li-Jun,Wu, Li-Nan,He, Ming-Feng,Qu, Jun-Wei,Zhao, Yi-Bing,Zhao, Wan-Zhou,Li, Jie-Shou,Wang, Jin-Hua Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.9

Objectives: To establish a taxol-resistant cell line of human ovarian carcinoma (A2780/Taxol) and investigate its biological features. Methods: The drug-resistant cell line (A2780/Taxol) was established by continuous stepwise selection with increasing concentrations of Taxol. Cell morphology was assessed by microscopy and growth curves were generated with in vitro and in vivo tumor xenograft models. With rhodamine123 (Rh123) assays, cell cycle distribution and the apoptotic rate were analyzed by flow cytometry (FCM). Drug resistance-related and signal associated proteins, including P-gp, MRPs, caveolin-1, PKC-${\alpha}$, Akt, ERK1/2, were detected by Western blotting. Results: A2780/Taxol cells were established with stable resistance to taxol. The drug resistance index (RI) was 430.7. Cross-resistance to other drugs was also shown, but there was no significant change to radioresistance. Compared with parental cells, A2780/Taxol cells were significantly heteromorphous, with a significant delay in population doubling time and reduced uptake of Rh123 (p<0.01). In vivo, tumor take by A2780 cells was 80%, and tumor volume increased gradually. In contrast, with A2780/Taxol cells in xenograft models there was no tumor development. FCM analysis revealed that A2780/Taxol cells had a higher percentage of G0/G1 and lower S phase, but no changes of G2 phase and the apoptosis rate. Expression of P-gp, MRP1, MRP2, BCRP, LRP, caveolin-1, PKC-${\alpha}$, Phospho-ERK1/2 and Phospho-JNK protein was significantly up-regulated, while Akt and p38 MARK protein expression was not changed in A2780/Taxol cells. Conclusion: The A2780/Taxol cell line is an ideal model to investigate the mechanism of muti-drug resistance related to overexpression of drug-resistance associated proteins and activation of the PKC-${\alpha}/ERK$ (JNK) signaling pathway.

Genome-wide association studies approach and post-GWAS study in rice

Gang Li,Min-Young Yoon,Won-Hee Ra,Jae-Wan Park,Qiang He,Aye Aye Khaing,Xiao-Qiang Wang,Win Htet Oo,Feng-Peng Li,Byoung Kook Yun,Chang-Yong Lee,Yong-Jin Park 한국육종학회 2013 한국육종학회 심포지엄 Vol.2013 No.07

AGenome-wide association studies (GWAS) have proven a useful technique for identifying genetic loci responsible for natural variation in rice. With the fast developed next-generation sequencing technology, it is possible for people to carry out GWAS by phenotyping different traits. However, how to make full use of huge data, abandon unnecessary data, and solve the problem of data application effectively seems still an obstacle for many researchers. Taking the case of whole-genome resequencing of Korean authentic rice core set, here we present a general technological path of GWAS including: 1) a schematic view of sequencing-based GWAS in rice; 2) a user-friendly and interactive web application for GWAS in rice by the aid of experience from Arabidopsis; 3) Haplotype and association analysis of candidate genes in a certain mechanism pathway, giving 10 starch synthesis genes as example; and 4) functional validation by Trans- and Mata-Omics analysis.

Green-revertible Chlorina 1 (grc1) is Required for the Biosynthesis of Chlorophyll and the Early Development of Chloroplasts in Rice

Jieqin Li,Yihua Wang,Juntao Chai,Lihua Wang,Chunming Wang,Wuhua Long,Di Wang,Yunlong Wang,Ming Zheng,Cheng Peng,Mei Niu,Jianmin Wan 한국식물학회 2013 Journal of Plant Biology Vol.56 No.5

The nuclear genes involved in chloroplast developmentand chlorophyll biosynthesis must be investigated tounderstand their functions in plant growth and development. In this study, we isolated and identified a unique leaf-colormutant of rice with a green-yellow phenotype before thefour-leaf stage and named the mutation green-revertiblechlorina 1 (grc1). The mutants had significantly lower plantheight, number of tillers, and panicle length and headedsignificantly earlier than the wild type. The levels ofchlorophylls, carotenoids, and chlorophyll precursors werealso lower. The mutation in grc1 affected chloroplastultrastructure, particularly thylakoid development. Geneticanalysis indicated that the green-yellow phenotype wascontrolled by a single recessive gene. We mapped the grc1gene to a 32.4-kb region on the long arm of chromosome 6. Through map-based cloning, we identified a 45-bp insertionin the genomic region of LOC_Os06g40080, which encodeda heme oxygenase. Expression of LOC_Os06g40080 wassignificantly down-regulated in the grc1 mutant. Subcellularlocalization showed that this heme oxygenase was localizedin the chloroplast. In summary, we isolated and identified thegene for grc1, which plays an important role in chlorophyllbiosynthesis and chloroplast development in rice.

SNPs of Excision Repair Cross Complementing Group 5 and Gastric Cancer Risk in Chinese Populations

Yang, Wan-Guang,Zhang, Shan-Feng,Chen, Ju-Wu,Li, Li,Wang, Wan-Peng,Zhang, Xie-Fu Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.12

We conducted a case-control study to determine the association between several potential SNPs of excision repair cross complementing group 5 (XPG) and gastric cancer susceptibility, and roles of XPG polymorphisms in combination with H.pylori infection in determining risk of gastric cancer. In our study, we collected 337 newly diagnosed gastric cancer cases and 347 health controls. Three SNPs of XPG, rs2296147T>C, rs2094258C>T and rs873601G>A, were genotyped using the Taqman real-time PCR method with a 7900 HT sequence detector system. H. pylori infection was diagnosed by ELISA. By multivariate logistic regression analysis, the rs2296147 CC genotype was associated with a decreased risk of gastric cancer (OR=0.52, 95% CI=0.27-0.97), and rs2094258 TT was associated with elevated risk (OR=2.13, 95% CI=1.22-3.35). Positive H.pylori individuals with rs2094258 TT genotypes demonstrated increased risk of gastric cancer (OR=2.13, 95% CI=1.22-3.35), while rs2296147 CC was associated with lower risk among patients with negative H.pylori (OR=0.45, 95%CI=0.22-0.89). Our findings suggested that XPG polymorphisms might contribute to risk of gastric cancer among Chinese populations, but the effect needs to be further validated by larger sample size studies.

New dammarane-type triterpenoid saponins from Panax notoginseng saponins

Qian Li,Mingrui Yuan,Xiaohui Li,Jinyu Li,Ming Xu,Di Wei,Desong Wu,Jinfu Wan,Shuangxi Mei,Tao Cui,Jingkun Wang,Zhaoyun Zhu 고려인삼학회 2020 Journal of Ginseng Research Vol.44 No.5

Background: Panax notoginseng saponin (PNS) is the extraction from the roots and rhizomes of Panax notoginseng (Burk.) F. H. Chen. PNS is the main bioactive component of Xuesaitong, Xueshuantong, and other Chinese patent medicines, which are all bestselling prescriptions in China to treat cardiocerebrovascular diseases. Notoginsenoside R₁ and ginsenoside Rg₁, Rd, Re, and Rb₁ are the principal effective constituents of PNS, but a systematic research on the rare saponin compositions has not been conducted. Objective: The objective of this study was to conduct a systematic chemical study on PNS and establish the HPLC fingerprint of PNS to provide scientific evidence in quality control. In addition, the cytotoxicity of the new compounds was tested. Methods: Pure saponins from PNS were isolated by means of many chromatographic methods, and their structures were determined by extensive analyses of NMR and HR-ESI-MS studies. The fingerprint was established by HPLC-UV method. The cytotoxicity of the compounds was tested by 3-(4,5-dimethylthiazol-2-yl)-2,5 -diphenyltetrazolium bromide assay. Results and Conclusion: Three new triterpenoid saponins (1e3) together with 25 known rare saponins (4 e28) were isolated from PNS, except for the five main compounds (notoginsenoside R₁ and ginsenoside Rg₁, Rd, Re, and Rb₁). In addition, the HPLC fingerprint of PNS was established, and the peaks of the isolated compounds were marked. The study of chemical constituents and fingerprint was useful for the quality control of PNS. The study on antitumor activities showed that new Compound 2 exhibited significant inhibitory activity against the tested cell lines.

The Beneficial Effects of Electroacupuncture at PC6 Acupoints (Neiguan) on Myocardial Ischemia in ASIC3 / mice

Ying-Wang,Yi-guo Chen,Wan-shuang Zhao,Di Li,Ya-han Xu,Meng-di Li,Jin Chen,Zhi-jun Kou,Qi-ge Wang,Nsoa dimitri Joseph 사단법인약침학회 2018 Journal of Acupuncture & Meridian Studies Vol.11 No.3

This study aims to investigate the possible mechanisms of electroacupuncture (EA) at PC6to improve myocardial ischemia (MI) by regulating the cardiac transient outward potassiumcurrent channel (Ito). According to the random number table, the mice were dividedinto six groups of six mice each: control group, MI group, PC6, LU7 (Lieque-point), ST36(Zusanli-point), and nonacupoint group. Mice in the control group were injected with saline(20 mg/kg, 24 hours interval), and the other ASIC3 / mice were injected subcutaneouslytwice with isoproterenol (ISO) (20 mg/kg, 24 hours interval). In thepreexperiment, 5 mg/kg, 10 mg/kg, 20 mg/kg, and 30 mg/kg of ISO were used, andthe results showed that 5 mg/kg and 10 mg/kg of ISO both could induce acute MI, butshorter duration of sustained MI. On the other hand, an injection of 30 mg/kg can makethe mice experience arrhythmia or die immediately, and EA was operated at PC6, LU7,ST36 acupoints, and nonacupoint in the mice of PC6, LU7, ST36, and nonacupoint groups,respectively, after injecting twice. Then Western blotting techniques (Western Blot) wereused to analyze the protein expressions of Kv1.4, Kv4.2, Kv4.3, and KchIP2. The results ofthis experiment showed that the protein expressions of Kv1.4, Kv4.2, Kv4.3, and KChIP2 inMI group were significantly lower than those in the control group (p < 0.01). Comparedwith MI group, the results of PC6, LU7, and ST36 groups obviously increased (p < 0.05). Furthermore, the expressions of PC6 group were higher than LU7 group and ST36 group(p < 0.05). And electrocardiogram’s T-waves showed obvious pathological changes inthe MI group compared to the control group (p < 0.01). After EA, the abnormal T-waves voltage of ECG in PC6, LU7, and ST36 groups was improved (p < 0.05). In addition, therate change of PC6 group was larger than that of both LU7 and ST36 groups (p < 0.05). But the T-waves voltage of the nonacupoint group was not significantly different than thatof the MI group (p > 0.05).

Stable Isotopes Reveal Water Vapor Sources of Precipitation over the Jiaolai Plain, Shandong Peninsula, China

Ying Wang,Bu-li Cui,Dong-sheng Li,Ya-xuan Wang,Wan-xin Yu,He-hua Zong 한국기상학회 2022 Asia-Pacific Journal of Atmospheric Sciences Vol.58 No.2

A prerequisite for using isotopic techniques to study the regional water cycle of a mountainous area is to examine the stable isotopic composition of precipitation. These findings are of great significance for an in-depth understanding of water cycle processes. In this study, each precipitation event was sampled and used to investigate the characteristics of stable hydrogen and oxygen isotopes in precipitation over the Jiaolai Plain and its surrounding areas. NCEP/NCAR data was used for the wind speed and direction, relative humidity, and precipitable amount in the study area during the sampling period. The water vapor sources of the precipitation over the plain were revealed through a comparative analysis of seasonal variations in precipitation isotopes between Global Network of Isotopes in Precipitation stations located along different vapor transport paths. The results showed that the local meteoric water line was δ2H = 6.38 δ18O + 0.72, with a gradient of less than 8. This indicates that the precipitation process was affected by non-equilibrium evaporation occurring when the drops fell below the cloud base. Temperature and amount effects were observed in the δ18O of the precipitation, although the altitude effect was not significant. The water vapor source of the precipitation was predominantly controlled by the East Asian Monsoon from June to September, with the primary source being evaporation from the adjacent Pacific Ocean. The plain was controlled by the Westerlies from October through May, with the predominant vapor source being local evaporation. Water vapor from the polar region had a minimal impact. These findings can serve as the basis for studying surface water–groundwater–seawater transformations.