Upregulation of PITX2 Promotes Letrozole Resistance Via Transcriptional Activation of IFITM1 Signaling in Breast Cancer Cells

Ying-ying Xu,Hai-ru Yu,Jia-yi Sun,Zhao Zhao,Shuang Li,Xin-feng Zhang,Zhi-xuan Liao,Ming-ke Cui,Juan Li,Chan Li,Qiang Zhang 대한암학회 2019 Cancer Research and Treatment Vol.51 No.2

Purpose Although the interferon  (IFN) signaling and the paired-like homeodomain transcription factor 2 (PITX2) have both been implicated in the progression of breast cancer (BCa), it remains obscure whether these two pathways act in a coordinated manner. We therefore aimed to elucidate the expression and function of PITX2 during the pathogenesis of endocrine resistance in BCa. Materials and Methods PITX2 expression was assessed in BCa tissues using quantitative reverse transcription polymerase chain reaction (RT-qPCR) and immunohistochemistry and in experimentally induced letrozole-resistant BCa cells using RT-qPCR and immunoblotting. Effects of PITX2 deregulation on BCa progression was determined by assessing MTT, apoptosis and xenograft model. Finally, using multiple assays, the transcriptional regulation of interferon-inducible transmembrane protein 1 (IFITM1) by PITX2 was studied at both molecular and functional levels. Results PITX2 expression was induced in letrozole-resistant BCa tissues and cells, and PITX2 induction by IFN signaling powerfully protected BCa cells against letrozole insult and potentiated letrozole-resistance. Mechanistically, PITX2 enhanced IFN-induced AKT activation by transactivating the transcription of IFITM1, thus rendering BCa cells unresponsive to letrozoleelicited cell death. Additionally, ablation of IFITM1 expression using siRNA substantially abolished IFN-elicited AKT phosphorylation, even in the presence of PITX2 overexpression, thus sensitizing BCa cells to letrozole treatment. Conclusion These results demonstrate that constitutive upregulation of PITX2/IFITM1 cascade is an intrinsic adaptive mechanism during the pathogenesis of letrozole-resistance, and modulation of PITX2/IFITM1 level using different genetic and pharmacological means would thus have a novel therapeutic potential against letrozole resistance in BCa.

Effectiveness and Safety of Dabrafenib in the Treatment of 20 Chinese Children with BRAFV600E-Mutated Langerhans Cell Histiocytosis

Ying Yang,Dong Wang,Lei Cui,Hong-Hao Ma,Li Zhang,Hong-Yun Lian,Qing Zhang,Xiao-Xi Zhao,Li-Ping Zhang,Yun-Ze Zhao,Na Li,Tian-You Wang,Zhi-Gang Li,Rui Zhang 대한암학회 2021 Cancer Research and Treatment Vol.53 No.1

Purpose We sought to investigate the effectiveness and safety of dabrafenib in children with BRAFV600E-mutated Langerhans cell histiocytosis (LCH). Materials and Methods A retrospective analysis was performed on 20 children with BRAFV600E-mutated LCH who were treated with dabrafenib. Results The median age at which the patients started taking dabrafenib was 2.3 years old (range, 0.6 to 6.5 years). The ratio of boys to girls was 2.3:1. The median follow-up time was 30.8 months (range, 18.9 to 43.6 months). There were 14 patients (70%) in the risk organ (RO)+ group and six patients (30%) in the RO– group. All patients were initially treated with traditional chemotherapy and then shifted to targeted therapy due to poor control of LCH or intolerance to chemotherapy. The overall objective response rate and the overall disease control rate were 65% and 75%, respectively. During treatment, circulating levels of cell-free BRAFV600E (cfBRAFV600E) became negative in 60% of the patients within a median period of 3.0 months (range, 1.0 to 9.0 months). Grade 2 or 3 adverse effects occurred in five patients. Conclusion Some children with BRAFV600E-mutated LCH may benefit from monotherapy with dabrafenib, especially high-risk patients with concomitant hemophagocytic lymphohistiocytosis and intolerance to chemotherapy. The safety of dabrafenib is notable. A prospective study with a larger sample size is required to determine the optimal dosage and treatment duration.

Illumina-based analysis of bacterial diversity related to halophytes Salicornia europaea and Sueada aralocaspica

Ying-wu Shi,Kai Lou,Chun Li,Lei Wang,Zhen-yong Zhao,Shuai Zhao,Chang-yan Tian 한국미생물학회 2015 The journal of microbiology Vol.53 No.10

We used Illumina-based 16S rRNA V3 amplicon pyrosequencing to investigate the community structure of soil bacteria from the rhizosphere surrounding Salicornia europaea, and endophytic bacteria living in Salicornia europaea plants and Sueada aralocaspica seeds growing at the Fukang Desert Ecosystem Observation and Experimental Station (FDEOES) in Xinjiang Province, China, using an Illumina genome analyzer. A total of 89.23 M effective sequences of the 16S rRNA gene V3 region were obtained from the two halophyte species. These sequences revealed a number of operational taxonomic units (OTUs) in the halophytes. There were between 22–2,206 OTUs in the halophyte plant sample, at the 3% cutoff level, and a sequencing depth of 30,000 sequences. We identified 25 different phyla, 39 classes and 141 genera from the resulting 134,435 sequences. The most dominant phylum in all the samples was Proteobacteria (41.61%–99.26%; average, 43.30%). The other large phyla were Firmicutes (0%– 7.19%; average, 1.15%), Bacteroidetes (0%–1.64%; average, 0.44%) and Actinobacteria (0%–0.46%; average, 0.24%). This result suggested that the diversity of bacteria is abundant in the rhizosphere soil, while the diversity of bacteria was poor within Salicornia europaea plant samples. To the extent of our knowledge, this study is the first to characterize and compare the endophytic bacteria found within different halophytic plant species roots using PCR-based Illumina pyrosequencing method.

Static behavior of bolt connected steel-concrete composite beam without post-cast zone

Ying Xing,Yun Zhao,Qi Guo,Jin-feng Jiao,Qing-wei Chen,Ben-zhao Fu 국제구조공학회 2021 Steel and Composite Structures, An International J Vol.38 No.4

Although traditional steel-concrete composite beams have excellent structural characteristics, it cannot meet the requirement of quick assembly and repair in the engineering. This paper presents a study on static behavior of bolt connected steel-concrete composite beam without post-cast zone. A three-dimensional finite element model was developed with its accuracy and reliability validated by available experimental results. The analysis results show that in the normal service stage, the bolt is basically in the state of unidirectional stress with the loss of pretightening can be ignored. Parametric studies are presented to quantify the effects of the post-cast zone, size and position of splicing gap on the behavior of the beam. Based on the studies, suggested size of gap and installation order were proposed. It is also confirmed that optimized concrete slab in mid-span can reduce the requirement of construction accuracy.

Chinese patent herbal medicine (Shufeng Jiedu capsule) for acute upper respiratory tract infections: A systematic review and meta-analysis

Ying-ying Zhang,Ru-yu Xia,Shi-bing Liang,Xiao-yang Hu,Meng-yuan Dai,Yi-lin Li,Le-yi Zhao,Michael Moore,Yu-tong Fei,Jian-ping Liu 한국한의학연구원 2021 Integrative Medicine Research Vol.10 No.3

Background: Shufeng Jiedu capsule has been widely used in China for acute upper respiratory tract infections (AURTIs). The aim of this study was to evaluate its effectiveness and safety for AURTIs. Methods: Randomized controlled trials comparing SFJD with conventional drug for patients with AURTIs were included. Eight databases were searched from their inceptions to February 2021. Data was synthesized using risk ration (RR) or mean difference (MD) with their 95% confidence interval (CI). The primary outcome was resolution time of typical symptoms. Results: Twenty-five RCTs involving 3410 patients were included. SFJD in combination with conventional drug was associated with; in common cold shortening the duration of fever (MD −1.54 days, 95% CI [−2.15,−0.92], I2 = 80%, n = 385, 3 trials) and cough (MD −1.22 days, 95% CI [−1.52, −0.93]); in herpangina, shortening the duration of fever (MD -0.68 days, 95% CI [−1.15, −0.21], I2 = 68%, n = 140, 2 trials) and blistering (MD −0.99 days, 95% CI [−1.23, −0.76], n = 386, 3 trials); in acute tonsillitis and acute pharyngitis shortening the duration of fever (MD −1.13 days, 95% CI [−1.36, −0.90], I2 = 33%, n = 688, 7 trials) and sore throat (MD −1.13 days, 95% CI [−1.40, −0.86], I2 = 84.1%, n = 1194, 10 trials). SFJD also improving their cure rate with a range (1–5 days). No serious adverse events were reported. Conclusion: Low certainty evidence suggests that SFJD appears to shorten the duration of symptoms in AURTIs, improve cure rate and seems safe for application. However, high quality placebo controlled trials are warranted to confirm its benefit.

Differential expression and functional analysis of circRNA in the ovaries of Yili geese at different egg-laying stages

Zhao Xiao-yu,Wu Ying-ping,Li Hai-ying,Cao Yan,Mei Zhi-yong,Li Jia-hui 한국유전학회 2022 Genes & Genomics Vol.44 No.10

Background: Ovarian development is regulated by genes that are expressed dynamically and stage-specifically. Circular RNA (circRNA) has been proven to play a significant role in the regulation of animal reproduction. Objective: Studying the expression characteristics of circRNAs in goose ovaries at various egg-laying stages can provide a reference for the molecular regulation mechanism of ovary development in geese that is mediated by circRNAs. Methods: In this study, the expression profiles of circRNAs were compared in ovary tissues from Yili geese in three different breeding periods, namely the prelaying period (KL), laying period (CL), and ceased period (XL), and differentially expressed circRNAs related to ovarian development in Yili geese were screened. The potential biological functions of differential circRNAs were predicted by bioinformatics, and the differential circRNA-miRNA regulatory network was constructed. Results: The results showed that a total of 4483 circRNAs were identified in 12 ovarian tissue samples from Yili geese at different laying stages. In the KL vs. CL, XL vs. CL, and XL vs. KL groups, 159, 455, and 383 differentially expressed circRNAs were identified, respectively. The host genes of the differential circRNAs were mostly enriched in the signal transduction, metabolism, and other related pathways, such as those for phototransduction, glycerophospholipid metabolism, aminoacyl-tRNA biosynthesis, and retinol metabolism. Finally, we constructed circRNA-miRNA regulation networks. Nine differential circRNAs were randomly selected for qRT-PCR verification, and the expression trends were consistent with the sequencing results. Conclusions: Our results indicated that significant differences in the expression profiles of circRNAs in the ovaries of Yili geese at different egg-laying stages. Meanwhile, through analyzing the differential circRNA-miRNA interaction network, core regulators such as circRNA NW_013186107.1:36835|52,574 and gga-miR-34b-5p were screened. This study provides a reference for the further analysis of the molecular regulatory mechanism of the circRNAs regulating goose ovary development and enriches the theory of genetic regulation during goose ovary development.

Anti-proliferation Effects of Interferon-gamma on Gastric Cancer Cells

Zhao, Ying-Hui,Wang, Tao,Yu, Guang-Fu,Zhuang, Dong-Ming,Zhang, Zhong,Zhang, Hong-Xin,Zhao, Da-Peng,Yu, Ai-Lian Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.9

IFN-${\gamma}$ plays an indirect anti-cancer role through the immune system but may have direct negative effects on cancer cells. It regulates the viability of gastric cancer cells, so we examined whether it affects their proliferation and how that might be brought about. We exposed AGS, HGC-27 and GES-1 gastric cancer cell lines to IFN-${\gamma}$ and found significantly reduced colony formation ability. Flow cytometry revealed no effect of IFN-${\gamma}$ on apoptosis of cell lines and no effect on cell aging as assessed by ${\beta}$-gal staining. Microarray assay revealed that IFN-${\gamma}$ changed the mRNA expression of genes related to the cell cycle and cell proliferation and migration, as well as chemokines and chemokine receptors, and immunity-related genes. Finally, flow cytometry revealed that IFN-${\gamma}$ arrested the cells in the G1/S phase. IFN-${\gamma}$ may slow proliferation of some gastric cancer cells by affecting the cell cycle to play a negative role in the development of gastric cancer.

8q24 rs4242382 Polymorphism is a Risk Factor for Prostate Cancer among Multi-Ethnic Populations: Evidence from Clinical Detection in China and a Meta-analysis

Zhao, Cheng-Xiao,Liu, Ming,Xu, Yong,Yang, Kuo,Wei, Dong,Shi, Xiao-Hong,Yang, Fan,Zhang, Yao-Guang,Wang, Xin,Liang, Si-Ying,Zhao, Fan,Zhang, Yu-Rong,Wang, Na-Na,Chen, Xin,Sun, Liang,Zhu, Xiao-Quan,Yuan Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.19

Background: Evidence supporting an association between the 8q24 rs4242382-A polymorphism and prostate cancer (PCa) risk has been reported in North American and Europe populations, though data from Asian populations remain limited. We therefore investigated this association by clinical detection in China, and meta-analysis in Asian, Caucasian and African-American populations. Materials and Methods: Blood samples and clinical information were collected from ethnically Chinese men from Northern China with histologically-confirmed PCa (n=335) and from age-matched normal controls (n=347). The 8q24 (rs4242382) gene polymorphism was genotyped by polymerase chain reaction-high-resolution melting analysis. We initially analyzed the associations between the risk allele and PCa and clinical covariates. A meta-analysis was then performed using genotyping data from a total of 1,793 PCa cases and 1,864 controls from our study and previously published studies in American and European populations, to determine the association between PCa and risk genotype. Results: The incidence of the risk allele was higher in PCa cases than controls (0.222 vs 0.140, $P=7.3{\times}10^{-5}$), suggesting that the 8q24 rs4242382-A polymorphism was associated with PCa risk in Chinese men. The genotypes in subjects were in accordance with a dominant genetic model (ORadj=2.03, 95%CI: 1.42-2.91, $Padj=1.1{\times}10^{-4}$). Presence of the risk allele rs4242382-A at 8q24 was also associated with clinical covariates including age at diagnosis ${\geq}65$ years, prostate specific antigen >10 ng/ml, Gleason score <8, tumor stage and aggressive PCa, compared with the non-risk genotype ($P=4.6{\times}10^{-5}-3.0{\times}10^{-2}$). Meta-analysis confirmed the association between 8q24 rs4242382-A polymorphism and PCa risk (OR=1.62, 95%CI: 1.39-1.88, $P=1.0{\times}10^{-5}$) across Asian, Caucasian and African American populations. Conclusions: The replicated data suggest that the 8q24 rs4242382-A variation might be associated with increased PCa susceptibility in Asian, Caucasian and African American populations. These results imply that this polymorphism may be a useful risk biomarker for PCa in multi-ethnic populations.

A Multi-center Survey of HPV Knowledge and Attitudes Toward HPV Vaccination among Women, Government Officials, and Medical Personnel in China

Zhao, Fang-Hui,Tiggelaar, Sarah M.,Hu, Shang-Ying,Zhao, Na,Hong, Ying,Niyazi, Mayinuer,Gao, Xiao-Hong,Ju, Li-Rong,Zhang, Li-Qin,Feng, Xiang-Xian,Duan, Xian-Zhi,Song, Xiu-Ling,Wang, Jing,Yang, Yun,Li, Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.5

Objectives: To assess knowledge of HPV and attitudes towards HPV vaccination among the general female population, government officials, and healthcare providers in China to assist the development of an effective national HPV vaccination program. Methods: A cross-sectional epidemiologic survey was conducted across 21 urban and rural sites in China using a short questionnaire. 763 government officials, 760 healthcare providers, and 11,681 women aged 15-59 years were included in the final analysis. Data were analyzed using standard descriptive statistics and logistic regression. Results: Knowledge of HPV among the general female population was low; only 24% had heard of HPV. Less than 20% of healthcare providers recognized sexually na$\ddot{i}$ve women as the most appropriate population for HPV vaccination. There was high acceptance of the HPV vaccine for all categories of respondents. Only 6% of women were willing to pay more than US $300 for the vaccine. Conclusions: Aggressive education is necessary to increase knowledge of HPV and its vaccine. Further proof of vaccine safety and efficacy and government subsidies combined with increased awareness could facilitate development and implementation of HPV vaccination in China.

Transport of a Novel Angiotensin-I-Converting Enzyme Inhibitory Peptide Ala-His-Leu-Leu Across Human Intestinal Epithelial Caco-2 Cells

Ying Li,Jiangtao Zhao,Xiaoli Liu,Xiudong Xia,Ying Wang,Jianzhong Zhou 한국식품영양과학회 2017 Journal of medicinal food Vol.20 No.3

The transport behavior and absorption mechanism of Ala-His-Leu-Leu (AHLL) intestinal absorption in Caco-2 cell monolayers were clarified systemically. The safe absorptive concentration of AHLL was 200 μg/mL, which was determined by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay. The permeation of AHLL was concentration dependent in a bidirectional transfer and reached a plateau at 90 min. The efflux ratio was above 0.5, suggesting that AHLL was absorbed by both active transport and passive diffusion. The apparent permeability coefficients (Papp) of AHLL both from the apical (AP) to basolateral (BL) side (PappAB) and from the BL to AP side (PappBA) decreased when the temperature was lowered from 37°C to 4°C.The uptake of AHLL was more at pH 7.4 than at other pHs. Both verapamil and (E)-3-[[[3-[2-(7-chloro-2- quinolinyl) ethenyl] phenyl]-[[(3-dimethyl amino)-3-oxopropyl]thio] methyl] thio]-propanoic acid (MK571) inhibited the absorption of AHLL, indicating that P-glycoprotein and multi-drug resistant proteins (MRPs) were all involved in AHLL secretion, especially multi-drug resistant protein 2 (MRP2). AHLL was transported through both trans- and paracellular pathways across the Caco-2 cell monolayer. This work first elucidates the AHLL absorption mechanism in Caco-2 cells and provides the basis for future studies on the improvement of bioavailability.