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Melatonin inhibits the Migration of Colon Cancer RKO cells by Down-regulating Myosin Light Chain Kinase Expression through Cross-talk with p38 MAPK

  • Zou, Duo-Bing;Wei, Xiao;Hu, Ruo-Lei;Yang, Xiao-Ping;Zuo, Li;Zhang, Su-Mei;Zhu, Hua-Qing;Zhou, Qing;Gui, Shu-Yu;Wang, Yuan
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.14
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    • pp.5835-5842
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    • 2015
  • Background: Melatonin, which is mainly produced by the pineal gland, has a good inhibitory effect on cell growth of multiple cancer types. However, the underlying molecular mechanisms of anti-tumor activity for colon cancer have not been fully elucidated. In this study, we investigated the effects of melatonin on migration in human colon cancer RKO cells and the potential molecular mechanisms. Materials and Methods: The viability of RKO cells was investigated by MTT assay after treatment with melatonin, SB203580 (p38 inhibitor) and phorbol 12-myristate 13-acetate (PMA, MAPK activator) alone or in combination for 48h. The effects of melatonin, and ML-7, a selective inhibitor of myosin light chain kinase (MLCK), and SB203580, and PMA on the migration of RKO cells were analyzed by in vitro scratch-wound assay. The relative mRNA levels of MLCK was assessed by real-time quantitative RT-PCR. Western blotting analysis was performed to examine the expression of MLCK, phosphorylation of myosin light chain (pMLC) and p38 (pp38). Results: The proliferation and migration of human colon cancer RKO cells were inhibited significantly after treatment with melatonin. The expression levels of MLCK and phosphorylation of MLC of RKO cells were reduced, and real-time quantitative RT-PCR showed that melatonin had significant effects on suppressing the expression of MLCK. Furthermore, the phosphorylation level of p38, which showed the same trend, was also reduced when cells were treated by melatonin. In addition, ML-7 (25umol/l) could down-regulate the phosphorylation of p38. Conclusions: Melatonin could inhibit the proliferation and migration of RKO cells, and further experiments confirmed that p38 MAPK plays an important role in regulating melatonin-induced migration inhibition through down-regulating the expression and activity of MLCK.

Systematic Review of Single Large and/or Multinodular Hepatocellular Carcinoma: Surgical Resection Improves Survival

  • Yang, Xiang-Di;Pan, Ling-Hui;Wang, Lin;Ke, Yang;Cao, Ji;Yang, Chun;Zhong, Jian-Hong;Luo, Wang;Guo, Jiao;Li, Le-Qun
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.13
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    • pp.5541-5547
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    • 2015
  • Background: The role of surgical resection for patients with single large (${\geq}5cm$) and/or multinodular (${\geq}2$) hepatocellular carcinoma (HCC) is still controversial. This systematic review was performed to evaluate the safety and efficacy of resection for patients with single large and/or multinodular HCC. Materials and Methods: Databases (the PubMed, Web of Science, Embase, and Cochrane databases) were systematically searched to identify relevant studies exploring the safety and efficacy of resection for single large and/or multinodular HCC, published between January 2000 and December 2014. Perioperative morbidity and mortality, overall survival, and disease-free survival of the resection group were calculated. In addition, these outcome variables were also calculated for the control group in the included studies. Results: One randomized controlled trial and 42 nonrandomized studies involving 9,580 patients were eligible for analysis. Eight (1,594 patients) of the 43 studies also reported the outcomes of transarterial chemoembolization (TACE). Although 51.4% of patients featured cirrhosis, 90.7% of them demonstrated Child-Pugh A liver function in the resection group. The median rates of morbidity (24.5%) and mortality (2.5%) after resection were significantly higher than that of TACE (11.0%, P<0.001; 1.9%, P<0.001). However, patients who underwent resection had significantly higher median one-, three-, and five-year overall survival (76.1%, 51.7%, and 37.4%) than those who underwent TACE (68.3%, 31.5%, and 17.5%, all P<0.001). The median 1-, 3-, and 5-year DFS rates after resection were 58.3%, 34.6%, and 24.0%, respectively. Conclusions: Although tumor recurrence after resection for patients with single large and/ or multinodular HCC continues to be a major problem, resection should be considered as a strategy to achieve long-term survival.

rs10505474 and rs7837328 at 8q24 Cumulatively Confer Risk of Prostate Cancer in Northern Han Chinese

  • Zhang, Lin-Lin;Sun, Liang;Zhu, Xiao-Quan;Xu, Yong;Yang, Kuo;Yang, Fan;Yang, Yi-Ge;Chen, Guo-Qiang;Fu, Ji-Cheng;Zheng, Chen-Guang;Li, Ying;Mu, Xiao-Qiu;Shi, Xiao-Hong;Zhao, Fan;Wang, Fei;Yang, Ze;Wang, Bin-You
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.7
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    • pp.3129-3132
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    • 2014
  • Aims: Genome-wide association studies (GWAS) have identified several risk variants for prostate cancer (pCa) mainly in Europeans, which need to be further verified in other racial groups. We selected six previously identified variants as candidates and to define the association with PCa in Northern Han Chinese. Methods: 749 subjects from Beijing and Tianjin in Northern China were included. Six variants (rs10505474, rs7837328, rs4242384, rs7813, rs486907 and rs1058205) were genotyped by high resolution melting (HRM) assays. The individual and cumulative contribution for of the risk of PCa and clinical covariates were analyzed. Results: Among the six candidate variants, onlyrs10505474, and rs7837328, both locating at 8q24 region, were associated with PCa in our population.rs10505474 (A) was associated with PCa ($OR_{recessive}=1.56$, p=0.006); and rs7837328 (A) was associated with PCa ($OR_{dominant}=1.38$, p=0.042/$OR_{recessive}=1.99$, p=0.003). Moreover, we observed a cumulative effects between them ($p_{trend}=2.58{\times}10^{-5}$). The joint population attributable risk showed the two variants might account for 71.85% of PCa risk. In addition, we found the homozygotes of rs10505474 (A) and rs7837328 (A) were associated with PCa clinical covariants (age at onset, tumor stage, respectively) ($p_{age}=0.046$, $P_{tumorstage}=0.048$). Conclusion: rs10505474 (A) and rs7387328 (A) at 8q24 are associated with PCa and cumulatively confer risk, suggesting the two variations could determine susceptibility to PCa in the Northern Chinese Han population.

Effects of Ribosomal Protein L39-L on the Drug Resistance Mechanisms of Lung Cancer A549 Cells

  • Liu, Hong-Sheng;Tan, Wen-Bin;Yang, Ning;Yang, Yuan-Yuan;Cheng, Peng;Liu, Li-Juan;Wang, Wei-Jie;Zhu, Chang-Liang
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.7
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    • pp.3093-3097
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    • 2014
  • Background: Cancer is a major threat to the public health whether in developed or in developing countries. As the most common primary malignant tumor, the morbidity and mortality rate of lung cancer continues to rise in recent ten years worldwide. Chemotherapy is one of the main methods in the treatment of lung cancer, but this is hampered by chemotherapy drug resistance, especially MDR. As a component of the 60S large ribosomal subunit, ribosomal protein L39-L gene was reported to be expressed specifically in the human testis and human cancer samples of various tissue origins. Materials and Methods: Total RNA of cultured drug-resistant and susceptible A549 cells was isolated, and real time quantitative RT-PCR were used to indicate the transcribe difference between amycin resistant and susceptible strain of A549 cells. Viability assay were used to show the amycin resistance difference in RPL39-L transfected A549 cell line than control vector and null-transfected A549 cell line. Results: The ribosomal protein L39-L transcription level was 8.2 times higher in drug-resistant human lung cancer A549 cell line than in susceptible A549 cell line by quantitative RT-PCR analysis. The ribosomal protein L39-L transfected cells showed enhanced drug resistance compared to plasmid vector-transfected or null-transfected cells as determined by methyl tritiated thymidine (3H-TdR) incorporation. Conclusions and Implications for Practice: The ribosomal protein L39-L gene may have effects on the drug resistance mechanism of lung cancer A549 cells.

Human Papillomavirus Vaccine Awareness, Acceptability, and Decision-Making Factors among Chinese College Students

  • Wang, Shao-Ming;Zhang, Shao-Kai;Pan, Xiong-Fei;Ren, Ze-Fang;Yang, Chun-Xia;Wang, Zeng-Zhen;Gao, Xiao-Hong;Li, Man;Zheng, Quan-Qing;Ma, Wei;Zhao, Fang-Hui;Qiao, You-Lin;Sivasubramaniam, Priya
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.7
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    • pp.3239-3245
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    • 2014
  • Background: College students are recommended as the target groups for catch-up human papillomavirus (HPV) vaccination. Systematical exploration of awareness, acceptability, and decision-making factors of HPV vaccination among Chinese college students has been limited. Materials and Methods: A multi-center survey was conducted in mainland China between November 2011 and May 2012. College students aged 18-22 years were stratified by their grade, gender, and major for sampling. Socio-demographic and HPV-related information such as knowledge, perceptions, acceptability, and attitudes were collected through a questionnaire. Results: A total of 3,497 undergraduates completed the questionnaire, among which 1,686 were males. The acceptability of the HPV vaccine was high (70.8%). Undergraduates from high-level universities, at lower grade, or with greater prior knowledge of HPV vaccines showed higher acceptability of HPV vaccination ($p_{trend}$ <0.001). Additionally, undergraduates with vaccination experience outside the National Expanded Program on Immunization (OR=1.29; 95%CI: 1.10-1.51) or fear of HPV-related diseases (OR=2.79; 95%CI: 2.28-3.41) were more willing to accept HPV vaccination. General knowledge of HPV vaccine was low among undergraduates, and safety was a major concern (71.05%). The majority of students wished to pay less than 300RMB for HPV vaccine and chose the Chinese Center for Disease Control and Prevention as the most appropriate venue for vaccination. Conclusions: Although most undergraduates demonstrate positive attitudes towards HPV vaccination, challenges pertaining to introduction exist in China. Corresponding proactive education and governmental subsidy to do so are urgently needed by this age-group population. Suggestions and potential strategies indicated may help shape the future HPV vaccination program in China.

Genetic Status of ESR Locus and Other Unidentified Genes As sociated with Litter Size in Chinese Indigenous Tongcheng Pig Breed after a Long Time Selection

  • Zhu, M.J.;Yu, M.;Liu, B.;Zhu, Z.Z.;Xiong, T.A.;Fan, B.;Xu, S.P.;Du, Y.Q.;Peng, Z.Z.;Li, K.
    • Asian-Australasian Journal of Animal Sciences
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    • v.17 no.5
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    • pp.598-602
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    • 2004
  • The Tongcheng pig breed is a famous Chinese indigenous breed. The Ministry of Agriculture of China has filed it as 1 of 19 national key conservation breeds selected from more than 100 Chinese indigenous pig breeds in 2000. In order to improve the reproductive performance, it has been intensively selected to increase the litter size for about 10 years. The population randomly sampled from conservation nucleus of eight families in the Tongcheng pigs was genotyped for identification of their estrogen receptor locus polymorphisms with the PCR-RFLPs method. Only AB heterozygotes and BB homozygotes were detected, and $X^2$ test demonstrated that the locus was in disequilibrium at a significant level (p<0.05). In the present paper, the litter sizes in different parities were regarded as different traits. Holistic status of other unspecific and unidentified genes was estimated by using the statistical methods. Coefficients of kurtosis and skewness showed that the litter size still presented segregating characteristic in the 2nd, 5th, 7th, 8th and 9th parities. Analysis of homogeneity of variance between families confirmed the results for the 5th, 7th and 8th parities. The heritability of litter size for the 1st to 10th parities was estimated with paternal half-sib model and individual estimated breeding values (EBVs) were evaluated by a single trait animal model as well. We found that the averages of EBVs for litter size in each parity did not differ significantly between genotypes, despite the significant difference for original phenotype records in the 3rd, 4th and 5th parities (p<0.05 or p<0.01). The results may be explained by the deduction that the polymorphisms of ESR locus are no longer the important genetic base of litter size variation when the frequency of allele B accumulated in the experience of selection procedure, and further conferring that there exist special genes associated with litter size in the recent Tongcheng pigs population can be made.

MINERAL NUTRITION OF GRAZING SHEEP IN NORTHERN CHINA II. SELENIUM, COPPER, MOLYBDENUM, IRON AND ZINC IN PASTURE, FEED SUPPLEMENTS AND SHEEP

  • Masters, D.G.;Purser, D.B.;Yu, S.X.;Wang, Z.S.;Yang, R.Z.;Liu, N.;Lu, D.X.;Wu, L.H.;Ren, J.K.;Li, G.H.
    • Asian-Australasian Journal of Animal Sciences
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    • v.6 no.1
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    • pp.107-113
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    • 1993
  • This study determined the concentrations of micro-minerals in pastures, in feed supplements and in grazing, reproducing ewes, at different times during the year, at three farms in Northern China. Samples were collected 5 to 8 times during the year and analysed for selenium, copper, iron, molybdenum and zinc. On two farms selenium concentrations in both pastures and animal tissues were low for part of the year. The lowest concentrations in pasture (< $30{\mu}g/kg$ DM) and liver (< $100{\mu}g/kg$ wet weight) indicated that productivity of the sheep may be reduced by a deficiency of this element. On one farm copper concentrations in the lever were in the liver were in the deficient range (< $5{\mu}g/kg$ wet weight) for part of the year. It is likely that this is a result of high intakes of iron from pasture (up to 4.5 g Fe/kg DM) and soil, as indicated by high concentrations of iron in faeces (up to 7 g Fe/kg DM). Molybdenum intake is unlikely to have had much influence on copper absorption because pasture concentrations of this element were not unusually high (1 to 5 mg/kg DM). Zinc in pastures on two farms was below 10 mg/kg DM for part of the year. On one of these farms, the concentration of zinc in faeces was below 30 mg/kg DM throughout the year and this is consistent with zinc intakes of 7 to 15 mg/kg. Despite these low intakes, the concentratons of zinc in plasma were consistently above deficient levels. No clinical signs of deficiencies of any of the elements studied were observed.

Effects of Inclusion Levels of Wheat Bran and Body Weight on Ileal and Fecal Digestibility in Growing Pigs

  • Huang, Q.;Su, Y.B.;Li, D.F.;Liu, L.;Huang, C.F.;Zhu, Z.P.;Lai, C.H.
    • Asian-Australasian Journal of Animal Sciences
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    • v.28 no.6
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    • pp.847-854
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    • 2015
  • The objective of this study was to determine the effects of graded inclusions of wheat bran (0%, 9.65%, 48.25% wheat bran) and two growth stages (from 32.5 to 47.2 kg and 59.4 to 78.7 kg, respectively) on the apparent ileal digestibility (AID), apparent total tract digestibility (ATTD) and hindgut fermentation of nutrients and energy in growing pigs. Six light pigs (initial body weight [BW] $32.5{\pm}2.1kg$) and six heavy pigs (initial BW $59.4{\pm}3.2kg$) were surgically prepared with a T-cannula in the distal ileum. A difference method was used to calculate the nutrient and energy digestibility of wheat bran by means of comparison with a basal diet consisting of corn-soybean meal (0% wheat bran). Two additional diets were formulated by replacing 9.65% and 48.25% wheat bran by the basal diet, respectively. Each group of pigs was allotted to a $6{\times}3$ Youden square design, and pigs were fed to three experimental diets during three 11-d periods. Hindgut fermentation values were calculated as the differences between ATTD and AID values. For the wheat bran diets, the AID and ATTD of dry matter (DM), ash, organic matter (OM), carbohydrates (CHO), gross energy (GE), and digestible energy (DE) decreased with increasing inclusion levels of wheat bran (p<0.05). While only AID of CHO and ATTD of DM, ash, OM, CHO, GE, and DE content differed (p<0.05) when considering the BW effect. For the wheat bran ingredient, there was a wider variation effect (p<0.01) on the nutrient and energy digestibility of wheat bran in 9.65% inclusion level due to the coefficient of variation (CV) of the nutrient and energy digestibility being higher at 9.65% compared to 48.25% inclusion level of wheat bran. Digestible energy content of wheat bran at 48.25% inclusion level (4.8 and 6.7 MJ/kg of DM, respectively) fermented by hindgut was significantly higher (p<0.05) than that in 9.65% wheat bran inclusion level (2.56 and 2.12 MJ/kg of DM, respectively), which was also affected (p<0.05) by two growth stages. This increase in hindgut fermentation caused the difference in ileal DE (p<0.05) to disappear at total tract level. All in all, increasing wheat bran levels in diets negatively influences the digestibility of some nutrients in pigs, while it positively affects the DE fermentation in the hindgut.

Effect of Priming and Seed Pellet Technique for Improved Germination and Growth in Fraxinus rhynchophylla and Alnus sibirica (프라이밍 및 종자펠렛 제조를 통한 물푸레나무와 물오리나무의 발아율 향상 및 생장증대 효과)

  • Park, Hae Il;Shim, Hoon Seob;Choi, Li Na;Jo, Hyeon Gil;Han, Seung Ho;Lee, Jae Geun;Yu, Chang Yeon;Lim, Jung Dae
    • Korean Journal of Medicinal Crop Science
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    • v.21 no.1
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    • pp.7-19
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    • 2013
  • This study was carried out to select new pelleting binder and material for seeds from Fraxinus rhynchophylla Hance and Alnus sibirica Fisch. ex Turcz. The optimum treatments of the various concentrations and species of priming agents to improve seed germination of both woody medicinal plants were also estimated. Germinability was increased when the seeds of Fraxinus rhynchophylla Hance was soaked in -1.0 MPa of PEG6000 solution at $15^{\circ}C$ for 4 days significantly, the optimum treatment for improving germination of Alnus sibirica Fisch. ex Turcz was observed when the tested seeds was soaked in 100 mM of KCl at $15^{\circ}C$ for 4 days. The influence of physical and chemical properties of pelleting solid materials, the mixture of gypsum, diatomaceous earth, dalma ceramic and vermicuolite (6:1:1:1 ratio) were found as the best pelleting materials for Fraxinus rhynchophylla Hance and Alnus sibirica Fisch. ex Turcz. seeds. To satisfy the requirements of absorption and compatibility for multi-layer seed pelleting, SGPA (Starch-grafted cross-linked polyacrylates) hydrogel was prepared using starch, acrylonitrile, ceric ammonium nitrate, nitric acid, methyl alcohol and potassium hydroxide. The resulting SGPA hydrogel showed high water absorption but not plant compatibility. It suggested that seed pelleting using pelleting materials and SGPA hydrogel (multi-layer coating) after priming agent treatment is to increase germinability and seedling growth and it can reduced irrigation labours and can also save seed.

Production and Characterization of Ethanol- and Protease-Tolerant and Xylooligosaccharides-Producing Endoxylanase from Humicola sp. Ly01

  • Zhou, Junpei;Wu, Qian;Zhang, Rui;Yang, Yuying;Tang, Xianghua;Li, Junjun;Ding, Junmei;Dong, Yanyan;Huang, Zunxi
    • Journal of Microbiology and Biotechnology
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    • v.23 no.6
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    • pp.794-801
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    • 2013
  • This paper reports the production and characterization of crude xylanase from the newly isolated Humicola sp. Ly01. The highest (41.8 U/ml) production of the crude xylanase was obtained under the optimized conditions (w/v): 0.5% wheat bran, 0.2% $KH_2PO_4$, and 0.5% peptone; initial pH 7.0; incubation time 72 h; $30^{\circ}C$; and 150 rpm. A considerable amount of the crude xylanase was induced using hulless barley bran or soybean meal as the carbon source, but a small amount of the enzyme was produced when supplementary urea was used as the nitrogen source to wheat bran. The crude xylanase showed apparent optimal cellulase-free xylanase activity at $60^{\circ}C$ and pH 6.0, more than 71.8% of the maximum xylanase activity in 3.0-30.0% (v/v) ethanol and more than 82.3% of the initial xylanase activity after incubation in 3.0-30.0% (v/v) ethanol at $30^{\circ}C$ for 2 h. The crude xylanase was moderately resistant to both acid and neutral protease digestion, and released 7.9 and 10.9 ${\mu}mol/ml$ reducing sugar from xylan in the simulated gastric and intestinal fluids, respectively. The xylooligosaccharides were the main products of the hydrolysis of xylan by the crude xylanase. These properties suggested the potential of the crude enzyme for being applied in the animal feed industry, xylooligosaccharides production, and high-alcohol conditions such as ethanol production and brewing.