Involvement of Cdc25c in Cell Cycle Alteration of a Radioresistant Lung Cancer Cell Line Established with Fractionated Ionizing Radiation

Li, Jie,Yang, Chun-Xu,Mei, Zi-Jie,Chen, Jing,Zhang, Shi-Min,Sun, Shao-Xing,Zhou, Fu-Xiang,Zhou, Yun-Feng,Xie, Cong-Hua Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.10

Cancer patients often suffer from local tumor recurrence after radiation therapy. Cell cycling, an intricate sequence of events which guarantees high genomic fidelity, has been suggested to affect DNA damage responses and eventual radioresistant characteristics of cancer cells. Here, we established a radioresistant lung cancer cell line, A549R, by exposing the parental A549 cells to repeated ${\gamma}$-ray irradiation with a total dose of 60 Gy. The radiosensitivity of A549 and A549R was confirmed using colony formation assays. We then focused on examination of the cell cycle distribution between A549 and A549R and found that the proportion of cells in the radioresistant S phase increased, whereas that in the radiosensitive G1 phase decreased. When A549 and A549R cells were exposed to 4 Gy irradiation the total differences in cell cycle redistribution suggested that G2-M cell cycle arrest plays a predominant role in mediating radioresistance. In order to further explore the possible mechanisms behind the cell cycle related radioresistance, we examined the expression of Cdc25 proteins which orchestrate cell cycle transitions. The results showed that expression of Cdc25c increased accompanied by the decrease of Cdc25a and we proposed that the quantity of Cdc25c, rather than activated Cdc25c or Cdc25a, determines the radioresistance of cells.

Identification of Cisplatin-Resistance Associated Genes through Proteomic Analysis of Human Ovarian Cancer Cells and a Cisplatin-resistant Subline

Zhou, Jing,Wei, Yue-Hua,Liao, Mei-Yan,Xiong, Yan,Li, Jie-Lan,Cai, Hong-Bing Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.12

Chemoresistance to cancer therapy is a major obstacle to the effective treatment of human cancers with cisplatin (DDP), but the mechanisms of cisplatin-resistance are not clear. In this study, we established a cisplatin-resistant human ovarian cancer cell line (COC1/DDP) and identified differentially expressed proteins related to cisplatin resistance. The proteomic expression profiles in COC1 before and after DDP treatment were examined using 2-dimensional electrophoresis technology. Differentially expressed proteins were identified using matrix-assisted laser desorption/ ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and high performance liquid chromatography-electrospray tandem MS (NanoUPLC-ESI-MS/MS). 5 protein spots, for cytokeratin 9, keratin 1, deoxyuridine triphosphatase (dUTPase), aarF domain containing kinase 4 (ADCK 4) and cofilin1, were identified to be significantly changed in COC1/DDP compared with its parental cells. The expression of these five proteins was further validated by quantitative PCR and Western blotting, confirming the results of proteomic analysis. Further research on these proteins may help to identify novel resistant biomarkers or reveal the mechanism of cisplatin-resistance in human ovarian cancers.

Versicolols A and B, two new prenylated isocoumarins from endophytic fungus Aspergillus versicolor and their cytotoxic activity

Min Zhou,Jie Lou,Yin-Ke Li,Yue-De Wang,Kun Zhou,Bing-Kun Ji,Wei Dong,Xue-Mei Gao,Gang Du,Qiu-Fen Hu 대한약학회 2017 Archives of Pharmacal Research Vol.40 No.1

Versicolols A and B (1 and 2), two rareprenylated isocoumarin derivatives, along with five knownisocoumarins (3–7) were isolated from the fermentationproducts of an endophytic fungus Aspergillus versicolor. Their structures were elucidated on the basis of extensivespectroscopic analysis, including 1D- and 2D-NMR techniques. Compounds 1 and 2 were evaluated for their cytotoxicityagainst five human tumor cell lines. The resultsshowed that compounds 1 exhibited weak cytotoxicityagainst A549 and MCF7 cells with IC50 values of 9.4 and8.8 lm, and compound 2 exhibited weak cytotoxicityagainst SHSY5Y and MCF7 cells with IC50 values of 8.2and 6.8 lm, respectively.

Effects of zearalenone on the localization and expression of the growth hormone receptor gene in the uteri of post-weaning piglets

Min Zhou,Li Jie Yang,Wei Ren Yang,Li Bo Huang,Xue Mei Zhou,Shu Zhen Jiang,Zai Bin Yang 아세아·태평양축산학회 2018 Animal Bioscience Vol.31 No.1

Objective: In this study, we investigated the adverse effects of dietary zearalenone (ZEA) (0.5 to 1.5 mg/kg diet) on the localization and expression of the growth hormone receptor (GHR) in the uteri of post-weaning gilts and explored alternative mechanism of the reproductive toxicity of ZEA on piglets. Methods: A total of forty healthy piglets (Duroc×Landrace×Large White) aged 28 d were selected for study. Piglets were transferred to single cages after 10 days’ adaptation on an obstetric table. The animals were allocated to one of four treatments: a normal basal diet supplemented with 0 (Control), 0.5 (ZEA0.5), 1.0 (ZEA1.0), or 1.5 (ZEA1.5) mg/kg purified ZEA, and fed for 35 d after the 10-d adaptation. Analyzed ZEA concentrations in the diets were 0, 0.52±0.07, 1.04±0.03, and 1.51±0.13 mg/kg, respectively. At the end of the feeding trial, piglets were euthanized after being fasted for 12 h. Two samples of uterine tissue from each pig were rapidly collected, one of which was stored at –80°C for analysis of the relative mRNA and protein expression of GHR, and the second was promptly fixed in Bouin’s solution for immunohistochemical analysis. Results: The relative weight of the uteri and thickness of the myometrium and endometrium increased linearly (p<0.001) and quadratically (p<0.001) with an increasing level of ZEA. The results of immunohistochemical analysis indicated that GHR immunoreactive substance was mainly localizated in the cytoplasm of uterine smooth muscle, glandular epithelial, luminal epithelial, stromal, and vascular endothelial cells. In contrast, nuclear staining was rarely observed. The immunoreactive integrated optic density of GHR in the myometrium, luminal epithelium, glandular epithelium, and whole uteri of weaning gilts increased linearly (p<0.001) and quadratically (p<0.05) with an increasing level of ZEA. The mRNA and protein expression of GHR in the uteri of weaning gilts increased linearly (p<0.001) and quadratically (p<0.05) with an increasing level of ZEA. Conclusion: In conclusion, ZEA at a concentration of 0.5 mg/kg was sufficient to significantly thicken the myometrium and endometrium, and at a concentration of 1.0 mg/kg induced a high level of GHR expression to promote growth and development of the uteri. This revealed an alternative molecular mechanism whereby ZEA induces growth and development of the uteri and provides a theoretical basis for the revision of Chinese feed hygiene standards.

Association of IgE-mediated allergen sensitivity and promoter polymorphisms of chemokine (C–C motif) ligand 5 gene in Han Chinese patients with allergic skin diseases

Ji-Chang Zhou,Yu-Mei Zhu,Zheng Chen,Shan He,Shi-jie Zheng,Jun-luan Mo,Xiao-Li Liu,Chun-mei Gong,Bin Hou,Hui Yang 한국유전학회 2015 Genes & Genomics Vol.37 No.5

Two single nucleotide polymorphisms (SNPs), rs2280788 (-28C[G) and rs2107538 (-403G[A), in the promoter region of chemokine (C–C motif) ligand 5 (CCL5) was reported to be involved in the immunoglobulin E (IgE) expression and IgE-mediated allergic reactions. This study was to investigate the characteristics of total serum IgE level, specific allergen sensitivities and the two SNPs in the allergic skin disease (ASD) patients. ASD patients visiting the dermatological outpatient department of a local hospital were included with certain criteria, and the fasting venous blood was sampled for analysis. Total serum IgE was assayed with an ELISA kit, and 14 kinds of allergen-specific IgE were tested with an allergen screening system. The polymerase chain reaction–restriction fragment length polymorphism method was used to analyze the two SNPs. Among the finally included 437 patients aged from 16 to 85 years, 68.2 % was positive for the total serum IgE, 49.2 % was positive for at least one of the assayed allergen-specific IgE, and 35.0 % was sensitive to house dust mite. In the SNPs analysis, the GG/(GA?AA) ratio and G/A ratio for the -403G[A locus in the male and/or female C45 years subgroup were significantly lower in the total serum IgE positive patients than in the negative patients (P\0.05). Weak linkage disequilibrium was found between -403A and -28C alleles in male subgroups adjusted by age. Conclusively, house dust mite was the most common allergen in ASD patients, and -403A allele of CCL5 promoter was a risk factor for IgE-mediated sensitization.

Continuous DC-CIK Infusions Restore CD8⁺ Cellular Immunity, Physical Activity and Improve Clinical Efficacy in Advanced Cancer Patients Unresponsive to Conventional Treatments

Zhao, Yan-Jie,Jiang, Ni,Song, Qing-Kun,Wu, Jiang-Ping,Song, Yu-Guang,Zhang, Hong-Mei,Chen, Feng,Zhou, Lei,Wang, Xiao-Li,Zhou, Xin-Na,Yang, Hua-Bing,Ren, Jun,Lyerly, Herbert Kim Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.6

Background: There are few choices for treatment of advanced cancer patients who do not respond to or tolerate conventional anti-cancer treatments. Therefore this study aimed to deploy the benefits and clinical efficacy of continuous dendritic cell-cytokine induced killer cell infusions in such patients. Materials and Methods: A total of 381 infusions (from 67 advanced cases recruited) were included in this study. All patients underwent peripheral blood mononuclear cell apheresis for the following cellular therapy and dendritic cells-cytokine induced killer cells were expanded in vitro. Peripheral blood T lymphocyte subsets were quantified through flow cytometry to address the cellular immunity status. Clinical efficacy and physical activities were evaluated by RECIST criteria and Eastern Cooperative Oncology Group scores respectively. Logistic regression model was used to estimate the association between cellular infusions and clinical benefits. Results: An average of $5.7{\pm}2.94{\times}10^9$ induced cells were infused each time and patients were exposed to 6 infusions. Cellular immunity was improved in that cytotoxic $CD8^+CD28^+$ T lymphocytes were increased by 74% and suppressive $CD8^+CD28^-$ T lymphocytes were elevated by 16% (p<0.05). Continuous infusion of dendritic cells-cytokine induced killer cells was associated with improvement of both patient status and cellular immunity. A median of six infusions were capable of reducing risk of progression by 70% (95%CI 0.10-0.91). Every elevation of one ECOG score corresponded to a 3.90-fold higher progression risk (p<0.05) and 1% increase of $CD8^+CD28^-$ T cell proportion reflecting a 5% higher risk of progression (p<0.05). Conclusions: In advanced cancer patients, continuous dendritic cell-cytokine induced killer cell infusions are capable of recovering cellular immunity, improving patient status and quality of life in those who are unresponsive to conventional cancer treatment.

Genetic variations in the bitter taste receptor gene TAS2R38 are related to cigarette smoking behavior in Han Chinese smokers

Qi Fei-Yan,Zhu Zhou-Hai,Li Meng,Guan Ying,Peng Qi-Yuan,Lu She-Ming,Liu Zhi-Hua,Wang Ming-Feng,Miao Ming-Ming,Chen Zhang-Yu,Li Xue-Mei,Bai Jie,Yao Jian-Hua 한국유전학회 2022 Genes & Genomics Vol.44 No.11

Background: Smoking behavior is influenced by multiple genes, including the bitter taste gene TAS2R38. It has been reported that the correlation between TAS2R38 and smoking behavior has ethnicity-based differences. However, the TAS2R38 status in Chinese smokers is still unclear. Objective: This study aims to investigate the possible relationship between genetic variations in TAS2R38 (A49P, V262A and I296V) and smoking behaviors in the Han Chinese population. Methods: The haplotype analyses were performed and smoking behavior questionnaire was completed by 1271 individuals. Genetic association analyses for smoking behavior were analyzed using chi-square test. Further, for investigating the molecular mechanism of TAS2R38 variants effect on smoking behavior, we conducted TAS2R38-PAV and TAS2R38-AVI expression plasmids and tested the cellular calcium assay by cigarette smoke compounds stimulus in HEK293. Results: Significant associations of genetic variants within TAS2R38 were identified with smoking behavior. We found a higher PAV/PAV frequency than AVI/AVI in moderate and high nicotine dependence (FTND ≥ 4; X2 = 4.611, 1 df, p = 0.032) and strong cigarette smoke flavor intensity preference (X2 = 4.5383, 1 df, p = 0.033) in participants. Furthermore, in the in vitro cellular calcium assay, total particle matter (TPM), N-formylnornicotine and cotinine, existing in cigarette smoke, activated TAS2R38-PAV but not TAS2R38-AVI-transfected cells. Conclusion: Our data highlights that genetic variations in TAS2R38 are related to smoking behavior, especially nicotine dependence and cigarette smoke flavor intensity preference. Our findings may encourage further consideration of the taste process to identify individuals susceptible to nicotine dependence, particularly Han Chinese smokers.

Isoindolin-1-ones from the stems of Nicotiana tabacum and their antiviral activities

Guang-Yu Yang,Jia-Meng Dai,Zhen-Jie Li,Jin Wang,Feng-Xian Yang,Xin Liu,Jing Li,Qian Gao,Xue-Mei Li,Yin-Ke Li,Wei-Guang Wang,Min Zhou,Qiu-Fen Hu 대한약학회 2022 Archives of Pharmacal Research Vol.45 No.8

In previous studies, several isoindolin-1-oneanalogs that exhibited signifi cant anti-tobacco mosaic virus(anti-TMV) activities were isolated from Nicotiana tabacum . Since gene-editing mutants provide a new sample for thediscovery of active metabolites, we focused on the stems ofYN-18–23 (a mutant N. tabacum for gene editing with thealkaloid metabolic pathway cultivated by Yunnan TobaccoCompany), which led to the isolation of four new ( 1–4 )and four known ( 5–8 ) isoindolin-1-ones. To the best of ourknowledge, nicindole C ( 3 ) is the fi rst subclass of isoindolin-1-one bearing a pentacyclic ketone, while nicindole D ( 4 )is the fi rst example of isoindolin-1-one bearing a methylpyridin-2-(1 H )-one moiety. Compounds 1–4 were testedfor their anti-TMV activities, and the results revealed thatcompounds 1 , 3 , and 4 exhibited high anti-TMV activities atconcentrations of 20 μM with inhibition rates of 48.6, 42.8,and 71.5%, respectively. These rates are higher than the inhibitionrate of the positive control (33.2%). The mechanisticstudy of compound 4 , which had the highest anti-TMV activityrevealed that increased potentiation of defense-related enzyme activities and downregulation of expression of theNtHsp70 protein may induce resistance in tobacco againstthe viral pathogen TMV. Molecular docking studies alsorevealed that the isoindolin-1-one substructure is fundamentalfor anti-TMV activity. The methyl-pyridin-2-(1 H )-onemoiety in compound 4 and the 2-oxopropyl groups in compounds1 and 3 at the N -2 position may increase inhibitoryactivities. This study of the structure–activity relationshipis helpful for fi nding new anti-TMV activity inhibitors. Tostudy whether the isoindolin-1-ones have broader antiviralactivities, compounds 1–4 were also tested for their antirotavirusactivities. Compound 4 exhibited high anti-rotavirusactivity with a therapeutic index (TI) value of 20.7. This TI value is close to that of the positive control (20.2).

The MDM2 SNP309T>G Polymorphism Increases Bladder Cancer Risk among Caucasians: a Meta-analysis

Wang, Huai-Gao,Wu, Qing-Yun,Zhou, Hui,Peng, Xin-Sheng,Shi, Meng-Jie,Li, Jie-Mei,Zhou, Yan-Fang Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.13

Published studies have evaluated associations between the MDM2 SNP309T>G polymorphism and bladder cancer susceptibility. However, these generated inconsistent results. The aim of the present investigation was to quantify the strength of association between MDM2 SNP309T>G polymorphism and bladder cancer risk by conducting a meta-analysis. We searched PubMed and Embase for related studies that had been published in English before April 1, 2014 and associations were assessed by summarizing the odds ratios (ORs) with the corresponding 95% confidence intervals (CIs). Five case-control studies with a total of 972 cases and 1,012 controls were finally identified to be eligible for the meta-analysis. Overall, the results indicated that there was no significant association between the MDM2 SNP309T>G polymorphism and bladder cancer risk (for the allele model G vs. T: OR=1.08, 95% CI 0.85-1.36, p=0.54; for the co-dominant model GG vs. TT: OR=1.20, 95% CI 0.74-1.93, p=0.46; for the dominant model GG+GT vs. TT: OR=0.98, 95% CI 0.80-1.20, p=0.83; for the recessive model GG vs. GT+TT: OR=1.20, 95% CI 0.83-1.74, p=0.33). However, on subgroup analysis by ethnicity, significant associations were found in Caucasians in three models (for the allele model G vs. T: OR=1.41, 95% CI 1.10-1.81, p=0.006; for the co-dominant model GG vs. TT: OR=2.16, 95% CI 1.28-3.63, p=0.004; for the recessive model GG vs. GT+TT: OR=2.06, 95% CI 1.31-3.22, p=0.002). In summary, the present meta-analysis provides evidence that the genotype for the MDM2 SNP309T>G polymorphism may be associated with genetic susceptibility to bladder cancer among Caucasians.

Dissecting the meteorological and genetic factors affecting rice grain quality in Northeast China

Chen Mojun,Li Zhao,Huang Jie,Yan Yongfeng,Wu Tao,Bian Mingdi,Zhou Jinsong,Wang Yongjun,Lyv Yanjie,Hu Guanghui,Jin Yong-Mei,Huang Kai,Guo Liping,Jiang Wenzhu,Du Xinglin 한국유전학회 2021 Genes & Genomics Vol.43 No.8

Background The Northeast Plain of China, which is an important region for the production of high grain quality rice in China. However, the grain quality of the rice produced varies across this region, even for the same cultivar. Objective In order to explore the meteorological factors that have the greatest infuence on quality and the transcriptional level diferences between diferent cultivars and diferent locations at grain flling stage. Methods We grew eight rice cultivars in three locations in Northeast China during two growing seasons (2017 and 2018). We recorded meteorological conditions, including air temperature, air temperature range, and photosynthetically active radiation (PAR) during the grain-flling stage of each cultivar, and analyzed the grain quality of those eight cultivars. Results Across all eight cultivars, meteorological factors had a stronger efect on eating quality than genotype, while genotype had a stronger efect on milling quality. Of the three environmental factors assessed, PAR was signifcantly correlated with the most grain quality traits. Using RNA-sequencing analysis, we identifed 573 environment-specifc DEGs (Diferentially Expressed Genes), and 119 genotype-specifc DEGs; 11 DEGs were responsive to genotype×environment interactions. These DEGs were involved in many key metabolic processes. Conclusion Our results indicated that interactions among environmental factors, especially PAR, afected rice quality in Northeast China. Further analyses of the DEGs identifed herein may provide useful information for future breeding programs aiming to develop high grain quality rice varieties suitable for cultivation across Northeast China.