An Ester Extract of Cochinchina Momordica Seeds Induces Differentiation of Melanoma B16 F1 Cells via MAPKs Signaling

Zhao, Lian-Mei,Han, Li-Na,Ren, Feng-Zhi,Chen, Shu-Hong,Liu, Li-Hua,Wang, Ming-Xia,Sang, Mei-Xiang,Shan, Bao-En Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.8

Cochinchina momordica seeds (CMS) have been widely used due to antitumor activity by Mongolian tribes of China. However, the details of the underlying mechanisms remain unknown. In the present study, we found that an EtOAc (ethyl ester) extract of CMS (CMSEE) induced differentiation and caused growth inhibition of melanoma B16 F1 cells. CMSEE at the concentration of $5-200{\mu}g/ml$ exhibited strongest anti-proliferative effects on B16 F1 cells among other CMS fractions (water or petroleum ether). Moreover, CMSEE induced melanoma B16 F1 cell differentiation, characterized by dendrite-like outgrowth, increasing melanogenesis production, as well as enhancing tyrosinase activity. Western blot analysis showed that sustained phosphorylation of p38 MAP accompanied by decrease in ERK1/2 and JNK dephosphorylation were involved in CMSEE-induced B16 F1 cell differentiation. Notably, 6 compounds that were isolated and identified may be responsible for inducing differentiation of CMSEE. These results indicated that CMSEE contributes to the differentiation of B16 F1 cells through modulating MAPKs activity, which may throw some light on the development of potentially therapeutic strategies for melanoma treatment.

Role of P14 and MGMT Gene Methylation in Hepatocellular Carcinomas: a Meta-analysis

Li, Cheng-Cheng,Yu, Zhuang,Cui, Lian-Hua,Piao, Jin-Mei,Liu, Meng Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.16

Background: This meta-analysis was performed to investigate the relationship between methylation of the P14 and O6-methylguanine-DNA methyltransferase (MGMT) genes and the risk of hepatocellular carcinoma (HCC). Materials and Methods: We searched PubMed, EMBASE, the Chinese Biomedical Database (CBM), and the China National Knowledge Infrastructure (CNKI) databases to identify relevant studies that analysed HCC tissues for P14 and MGMT gene methylation status; we then performed a meta-analysis. Odds ratios (ORs) and 95% confidence intervals (95%CIs) were calculated to evaluate the association between gene methylation and the risk of HCC. Results: Ten studies that assessed P14 gene methylation in 630 HCC tumour tissues and nine studies analysing MGMT methylation in 497 HCC tumour tissues met our inclusion criteria. Our meta-analysis revealed that the rate of P14 methylation was significantly higher in HCCs than in adjacent tissues (OR 3.69, 95%CI 1.63-8.35, p=0.002), but there was no significant difference in MGMT methylation between HCC and adjacent tissues (OR 1.76, 95%CI 0.55-5.64, p=0.34). A subgroup analysis according to ethnicity revealed that P14 methylation was closely related to the risk of HCC in Chinese and Western individuals (Chinese, OR 7.74, 95%CI 1.36-44.04, p=0.021; Western, OR 3.60, 95%CI 1.49-8.69, p=0.004). Furthermore, MGMT methylation was not correlated with the risk of HCC in Chinese individuals (OR 2.42, 95%CI 0.76-7.73, p=0.134). The combined rate of P14 methylation was 35% (95%CI 24-48%) in HCC tumour tissues and 11% (95%CI 4-27%) in adjacent tissues, whereas the combined rate of MGMT methylation was 15% (95%CI 6-32%) in HCC and 10% (95%CI 4-22%) in adjacent tissues. Conclusions: These results suggest that the risk of HCC is related to P14 methylation, but not MGMT methylation. Therefore, P14 gene methylation may be a potential biomarker for the diagnosis of HCC.

Prospective comparison of hybrid capture 2 and SPF10-LiPA for carcinogenic human papillomavirus detection and risk prediction of cervical cancer: a population-based cohort study in China

Li Dong,Rui-Mei Feng,Li Zhang,Xiao-qian Xu,Xue-Lian Zhao,Margaret Zhuoer Wang,You-Lin Qiao,Fang-Hui Zhao 대한부인종양학회 2017 Journal of Gynecologic Oncology Vol.28 No.5

Objective: To investigate the extent of the cross-reactivity of hybrid capture 2 (HC2) assay andevaluate the potential effect of cross-reactivity on the long-term risk for cervical cancer andprecancers. Methods: Based on the Shanxi Province Cervical Cancer Screening Study-I (SPOCCS-I)cohort from 2005 to 2014 in Shanxi, China, SPF10-line probe assay (LiPA) was performedin all 598 HC2 positive and 300 random-selected HC2 negative cervical specimens. Tenyearcumulative incidence rate (CIR) of cervical intraepithelial neoplasia grade 2 or worse(CIN2+) of these two tests was evaluated using Kaplan-Meier methods. Possible humanpapillomavirus (HPV) types to be cross-reacted by HC2 were also analyzed. Results: The overall agreement between HC2 and SPF10-LiPA for detecting carcinogenic HPVwas 73.27%. The highest 10-year cumulative risk of CIN2+ was observed in both HC2 positiveand LiPA-carcinogenic HPV positive women (25.70%; 95% confidence interval [CI]=23.55%–27.91%), followed by HC2 positive but LiPA-non-carcinogenic HPV positive women (9.97%;95% CI=8.57%–11.50%), HC2 negative but LiPA-carcinogenic HPV positive (2.56%; 95%CI=2.44%–2.70%) and HC2 positive but LiPA-HPV negative (1.85%; 95% CI=1.78%–1.92%)women. The proportion of cross-reactivity of HC2 with untargeted carcinogenic types was8.9%, most of which were attributable to HPV26, 73, 82, 69, 71, 53, 11, 43, and 54. Conclusion: The noticeable high risk of CIN2+ in women infected with cross-reacted noncarcinogenicHPV and low risk in those with miss-to-detective carcinogenic HPV supportedan overall good clinical performance of HC2 for a general cervical cancer screening.

MiRNA-15a Mediates Cell Cycle Arrest and Potentiates Apoptosis in Breast Cancer Cells by Targeting Synuclein-γ

Li, Ping,Xie, Xiao-Bing,Chen, Qian,Pang, Guo-Lian,Luo, Wan,Tu, Jian-Cheng,Zheng, Fang,Liu, Song-Mei,Han, Lu,Zhang, Jian-Kun,Luo, Xian-Yong,Zhou, Xin Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.16

Background: Recent studies have indicated that microRNA-15a (miR-15a) is dysregulated in breast cancer (BC). We aimed to evaluate the expression of miR-15a in BC tissues and corresponding para-carcinoma tissues. We also focused on effects of miR-15a on cellular behavior of MDA-MB-231 and expression of its target gene synuclein-${\gamma}$ (SNCG). Materials and Methods: The expression levels of miR-15a were analysed in BC formalin fixed paraffin embedded (FFPE) tissues by microarray and quantitative real-time PCR. CCK-8 assays, cell cycle and apoptosis assays were used to explore the potential functions of miR-15a in MDA-MB-231 human BC cells. A luciferase reporter assay confirmed direct targets. Results: Downregulation of miR-15a was detected in most primary BCs. Ectopic expression of miR-15a promoted proliferation and suppressed apoptosis in vivo. Further studies indicated that miR-15a may directly interact with the 3'-untranslated region (3'-UTR) of SNCG mRNA, downregulating its mRNA and protein expression levels. SNCG expression was negatively correlated with miR-15a expression. Conclusions: MiR-15a has a critical role in mediating cell cycle arrest and promoting cell apoptosis of BC, probably by directly targeting SNCG. Thus, it may be involved in development and progression of BC.

Biochemical Characterization of a GDSL-Motif Esterase from Bacillus sp. K91 with a New Putative Catalytic Mechanism

( Jun Mei Ding ),( Ting Ting Yu ),( Lian Ming Liang ),( Zhen Rong Xie ),( Yun Juan Yang ),( Jun Pei Zhou ),( Bo Xu ),( Jun Jun Li ),( Zun Xi Huang ) 한국미생물 · 생명공학회 2014 Journal of microbiology and biotechnology Vol.24 No.11

The esterase gene Est8 from the thermophilic bacterium Bacillus sp. K91 was cloned and expressed in Escherichia coli. The monomeric enzyme exhibited a theoretical molecular mass of 24.5 kDa and an optimal activity around 50°C at pH 9.0. A model of Est8 was constructed using a hypothetical YxiM precursor structure (2O14_A) from Bacillus subtilis as template. The structure showed an α/β-hydrolase fold and indicated the presence of a typical catalytic triad consisting of Ser-11, Asp-182, and His-185, which were investigated by site directed replacements coupled with kinetic characterization. Asp-182 and His-185 residues were more critical than the Ser-11 residue in the catalytic activity of Est8. A comparison of the amino acid sequence showed that Est8 could be grouped into the GDSL family and further classified as an SGNH hydrolase. Est8 is a new member of the SGNH hydrolase subfamily and may employ a different catalytic mechanism.

LncRNA A2M-AS1 lessens the injury of cardiomyocytes caused by hypoxia and reoxygenation via regulating IL1R2

Xue‑Lian Song,Fei‑Fei Zhang,Wen‑Jing Wang,Xin‑Ning Li,Yi Dang,Ying‑Xiao Li,Qian Yang,Mei‑Jing Shi,Xiao‑Yong Qi 한국유전학회 2020 Genes & Genomics Vol.42 No.12

Background: Myocardial ischemia and reperfusion injury (MI/RI) is a complex pathophysiological process, which can lead to severe myocardial injury. The long noncoding RNA alpha-2-macroglobulin antisense RNA 1 (A2M-AS1) has been revealed to be abnormally expressed in MI, However, its function in MI and the potential mechanism are still unclear. Objective: To evaluate the functional role of A2M-AS1 in hypoxia/reoxygenation (H/R)-induced neonatal cardiomyocytes and its potential molecular mechanism. Methods: Dataset GSE66360 was obtained from GEO database for analyzing the RNA expression of A2M-AS1 and interleukin 1 receptor type 2 (IL1R2). KEGG pathway enrichment analysis of the genes that co-expressed with A2M-AS1 was performed. Human neonatal cardiomyocytes were subjected to H/R to construct in vitro models. QRT-PCR and Western blot were adopted to test the levels of mRNA and protein. The viability and apoptosis of cardiomyocytes were tested by CCK-8 and flow cytometry assays, respectively. Results: The expression of A2M-AS1 was notably downregulated in H/R-treated cardiomyocytes. Overexpression of A2M-AS1 can notably enhance the cell viability of H/R-damaged cardiomyocytes, whereas knockdown of A2M-AS1 showed the opposite outcomes. Besides, a negative correlation was showed between A2M-AS1 and IL1R2 expression. In H/R-treated cardiomyocytes, overexpression of IL1R2 weakened the promoting proliferation and anti-apoptosis effects caused by overexpressing A2M-AS1, however, IL1R2-knockdown abolished the anti-proliferation and pro-apoptosis effects caused by silencing A2M-AS1. Conclusion: This study demonstrates the potential regulatory role of A2M-AS1/ IL1R2 axis in cardiomyocytes suffered from H/R, and provides insight into the protection of MI/RI.

High­risk human papillomavirus genotype distribution and attribution to cervical cancer and precancerous lesions in a rural Chinese population

Xue-Lian Zhao,Shang-Ying Hu,Qian Zhang,Li Dong,Rui-Mei Feng,Ross Han,Fang-Hui Zhao 대한부인종양학회 2017 Journal of Gynecologic Oncology Vol.28 No.4

Objective: To explore the genotype distribution of high-risk human papillomavirus (HR-HPV) and its attribution to different grades of cervical lesions in rural China, which will contribute to type-specific HPV screening tests and the development of new polyvalent HPV vaccines among the Chinese population. Methods: One thousand two hundred ninety-two subjects were followed based on the Shanxi Province Cervical Cancer Screening Study I (SPOCCS-I), and screened by HPV DNA testing (hybrid capture® 2 [HC2]), liquid-based cytology (LBC), and if necessary, directed or random colposcopy-guided quadrant biopsies. HPV genotyping with linear inverse probe hybridization (SPF10-PCR-LiPA) was performed in HC2 positive specimens. Attribution of specific HR-HPV type to different grades of cervical lesions was estimated using a fractional contribution approach. Results: After excluding incomplete data, 1,274 women were included in the final statistical analysis. Fifteen point two percent (194/1,274) of women were HR-HPV positive for any of 13 HR-HPV types (HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68) and the most common HR-HPV types were HPV16 (19.1%) and HPV52 (16.5%). The genotypes most frequently detected in HR-HPV-positive cervical intraepithelial neoplasia grade 1 (CIN1) were HPV52 (24.1%), HPV31 (20.7%), HPV16 (13.8%), HPV33 (13.8%), HPV39 (10.3%), and HPV56 (10.3%); in HR-HPV-positive cervical intraepithelial neoplasia grade 2 or worse (CIN2+): HPV16 (53.1%), HPV58 (15.6%), HPV33 (12.5%), HPV51 (9.4%), and HPV52 (6.3%). HPV52, 31, 16, 33, 39, and 56 together contributed to 89.7% of HR-HPV-positive CIN1, and HPV16, 33, 58, 51, and 52 together contributed to 87.5% of CIN2+. Conclusion: In summary, we found substantial differences in prevalence and attribution of CINs between different oncogenic HPV types in a rural Chinese population, especially for HPV16, 31, 33, 52, and 58. These differences may be relevant for both clinical management and the design of preventive strategies.

청소년 온/오프라인 비행에 영향을 미치는 요인에 대한 메타분석: 비행 이론을 중심으로

김부경,Lian mei li,박지수,송태민 한국교육학회 2023 敎育學硏究 Vol.61 No.8

General strain theory, routine activity theory, self-control theory, social learning theory, and social bond theory are representative theories to explain the causes of juvenile delinquency. However, as online delinquency emerges, it is necessary to verify whether the aforementioned theories can be adopted for both online and offline delinquency. To examine these theories, this study identified 76 empirical articles on South Korea adolescents that utilized one of these theories. Using meta-analysis, this study found that there was a statistically significant difference in the effect size among theories. The effect of social learning theory (ES: 0.29, p < .001) on delinquency was highest, followed by self-control theory (ES: -0.20 p < .001), routine activity theory (ES: -0.19, p < .001), general strain theory (ES: -0.17, p < .001), and social bond theory (ES: -0.16, p < .001). Furthermore, the moderation effect of online and offline delinquency on the theories was only statistically significant according to general strain theory. The effect size of offline delinquency was larger than the effect size of online delinquency. Findings of this study will be used to utilize more effective factors for future studies and interventions.

Regulatory effect of peroxiredoxin 1 (PRDX1) on doxorubicin-induced apoptosis in triple negative breast cancer cells

Han Ying-Hao,Lian Xu-Dong,Lee Seung-Jae,Li Wei-Long,Sun Hu-Nan,Jin Mei-Hua,Kwon Taeho 한국응용생명화학회 2022 Applied Biological Chemistry (Appl Biol Chem) Vol.65 No.5

Patients with triple negative breast cancer (TNBC) lack the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2; thus, conventional hormone and targeted therapies have minimal effect on them. Therefore, clinical treatment of TNBC is still based on chemotherapy and supplemented by other methods. Doxorubicin (DOX), a common drug used in TNBC chemotherapy, has high affinity for cardiolipin, and the nematosomes are rich in cardiolipin; therefore, DOX has high mitochondria-targeting ability. DOX accumulates and plunders the electrons of nicotinamide adenine dinucleotide phosphate (NADPH) and cytochrome C in mitochondria to produce semiquinone DOX. Under the action of oxygen molecules, semiquinone DOX is reduced to DOX and reactive oxygen species (ROS) are generated. The accumulation of ROS can cause mitochondrial dysfunction and lead to mitochondrial dependent apoptosis. Bioinformatic analysis of samples from TNBC patients revealed that peroxiredoxin 1 (PRDX1) was highly expressed in TNBC tissues, and the poor prognosis of patients with high PRDX1 expression was considerably increased. Previous studies determined that DOX can upregulate the expression of the PRDX1 protein in the human TNBC cell line (MDA-MB-231). Thus, we speculate that PRDX1 plays an important role in the process of DOX-induced TNBC cell apoptosis. In this study, we aimed to explore the role of PRDX1 in the process of DOX-induced TNBC cell apoptosis. We found that PRDX1 deletion increased the sensitivity of MDA-MB-231 cells to DOX, which was mainly due to mitochondrial oxidative stress caused by intracellular ROS accumulation, leading to mitochondriadependent apoptosis. Deletion of PRDX1 promotes the PI3K/Akt signaling pathway to mediate the expression of GSK3β. Gsk3β is an upstream signal of mitochondria-dependent apoptosis, and is also an important target of ROS. PRDX1 participates in adriamycin-induced apoptosis of TNBC cells by regulating the expression level of GSK3β. Our findings present new insights to treat breast cancer and TNBC, outlines the clinical use of DOX, and provides a basic theory to develop PRDX1 gene function.

Molecular and Functional Characterization of ZmNF-YC14 in Transgenic Arabidopsis

Yilin Cai,Xiupeng Mei;Ping Li;Lu Wang;Chaoxian Liu;Lian Zhou 한국식물학회 2018 Journal of Plant Biology Vol.61 No.6

The optimum transition stage from vegetative toreproductive development is important for flowering plantsto obtain the desired plant architecture to maximize yield. Inthis study, we overexpressed the maize NUCLEAR FACTORY, SUBUNIT C 14 (ZmNF-YC14) gene in Arabidopsis toinvestigate its potential functions in the regulation of planttransition. Overexpression of ZmNF-YC14 in Arabidopsisinhibited plant flowering and retarded the duration of thebranch-producing inflorescence phase 1 (I1). These plantsexhibited increased length of I1 and higher ratio of inflorescencephase 1 to inflorescence phase (I) (I1:I) under long-dayconditions. As a consequence, these transgenic plants exhibiteddramatic changes in their overall inflorescence morphology. In addition, the phenotypes of inflorescence morphologycaused by ZmNF-YC14 overexpression were enhanced byexogenous gibberellin (GA) treatment, which obtained asignificant increase in I1:I, inflorescence phase 1 to inflorescencephase 2 (I2) (I1:I2), and remarkable decrease in I2 and I2:I intransgenic plants compared to those under normal conditions. Taken together, the results of this study suggest that ZmNFYC14negatively regulates flowering and controls flowerformation under long-day conditions in Arabidopsis and maybe involved in a GA regulation pathway.