Mitochondria-mediated Apoptosis in Human Lung Cancer A549 Cells by 4-Methylsulfinyl-3-butenyl Isothiocyanate from Radish Seeds

Wang, Nan,Wang, Wei,Huo, Po,Liu, Cai-Qin,Jin, Jian-Chang,Shen, Lian-Qing Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.5

4-Methylsulfinyl-3-butenyl isothiocyanate (MTBITC) found in the radish (Raphanus sativus L.), is a wellknown anticancer agent. In this study, the mechanisms of the MTBITC induction of cell apoptosis in human A549 lung cancer cells were investigated. Our PI staining results showed that MTBITC treatment significantly increased the apoptotic sub-G1 fraction in a dose-dependent manner. The mechanism of apoptosis induced by MTBITC was investigated by testing the change of mitochondrial membrane potential (${\Delta}{\Psi}m$), the expression of mRNAs of apoptosis-related genes by RT-PCR, and the activities of caspase-3 and -9 by caspase colorimetric assay. MTBITC treatment decreased mitochondrial membrane potential by down-regulating the rate of Bcl-2/Bax and Bcl-xL/Bax, and activation of caspase-3 and -9. Therefore, mitochondrial pathway and Bcl-2 gene family could be involved in the mechanisms of A549 cell apoptosis induced by MTBITC.

Order–disorder structural tailoring and its effects on the chemical stability of (Gd, Nd)2(Zr, Ce)2O7 pyrochlore ceramic for nuclear waste forms

Wang Yan,Wang Jin,Zhang Xue,Li Nan,Wang Junxia,Liang Xiaofeng 한국원자력학회 2022 Nuclear Engineering and Technology Vol.54 No.7

Series of unequal quantity Nd/Ce co-doped ceramic nuclear waste forms, (Gd, Nd)2(Zr, Ce)2O7, were prepared to tailor its ordered pyrochlore or disordered fluorite structure. The phase transition, microtopography, and elemental composition of the ceramic samples were systematically investigated, especially the effect of order-disorder structure on the chemical stability. It was confirmed that unequal quantity of Nd/Ce could synchronously replace the Gd/Zr-sites of Gd2Zr2O7. And the phase transition of order-disorder structure could be successfully tailored by regulating the average cationic radius ratio of (Gd, Nd)2(Zr, Ce)2O7 series. The elements of Gd, Nd, Zr, and Ce are uniformly distributed in the ordered or disordered structures. The MCC-1 leaching results showed that (Gd, Nd)2(Zr, Ce)2O7 pyrochlore ceramic nuclear waste forms had excellent chemical stability, whose elements' normalized leaching rates were as low as 104 -107 g‧m2 ‧d1 after 7 days. In particular, the chemical stability of disordered structure was superior to that of ordered structure. It was proposed that the force constant and the closest packing were changed with the structure transformation resulting the chemical stability difference

Relationship Between Mindfulness and Affiliate Stigma in Parents of Children with Autism Spectrum Disorder in China: The Mediating Role of Coping Styles

Ya-Nan Wang,Qi-Heng Lin,Dan Meng,Jing Wang,Hai-Ping Xu,Wan-Hong Wei,Jin-Yan Zhang 한국간호과학회 2024 Asian Nursing Research Vol.18 No.2

PurposeThis study aims to investigate the current status of affiliate stigma among parents of autistic children, analyze the influencing factors, explore the relationship among mindfulness, coping styles, and affiliate stigma, and verify the mediating role of coping styles between mindfulness and affiliate stigma in parents of children with autism in China. MethodBetween February and April 2023, the Child Development Behaviour Centre of a public hospital in China recruited 345 parents of children with autism. These parents completed the general information questionnaire, the Mindful Attention Awareness Scale, the Affiliate Stigma Scale, and the Simple Coping Style Questionnaire. We then adapted the Hayes Process Macro and Bootstrap methods to examine the mediating effects of coping styles between mindfulness and affiliate stigma. Results(1) The total affiliate stigma score of parents of children with autism was 48.53 (standard deviation:: 10.74). Parents' age, monthly family income, duration of care, mindfulness, and coping styles were the influencing factors of parental affiliate stigma. (2) Mindfulness was positively correlated with positive coping style (r = 0.33, p < .01) and negatively correlated with negative coping style, affiliate stigma (r = −0.38, −0.39, p < .01), whereas affiliate stigma was negatively correlated with positive coping style (r = −0.34, p < .01) and positively correlated with negative coping style (r = 0.41, p < .01). (3) Positive coping style and negative coping style play a parallel mediating role between mindfulness and affiliate stigma of parents of autistic children. ConclusionsParents of children with autism experience significant levels of affiliate stigma. Mindfulness has a direct impact on associated stigma in parents of children with autism and also indirectly predicts associated stigma through the intermediary influence of positive and negative coping styles. Healthcare professionals could perform mindfulness interventions from an optimistic psychology viewpoint to boost parents' mindfulness and coping abilities, thereby accomplishing the objective of mitigating affiliate stigma.

The Characteristics and Survival Outcomes in Patients Aged 70 Years and Older with Nasopharyngeal Carcinoma in the Intensity-Modulated Radiotherapy Era

Ya-Nan Jin,Wang-Jian Zhang,Xiu-Yu Cai,Mei-Su Li,Wayne R. Lawrence,Si-Yang Wang,Dong-Mei Mai,Yu-Yun Du,Dong-Hua Luo,Hao-Yuan Mo 대한암학회 2019 Cancer Research and Treatment Vol.51 No.1

Purpose We aim to examine nasopharyngeal carcinoma (NPC) characteristics and survival outcomes in patients aged 70 years and older in the intensity-modulated radiotherapy (IMRT) era. Materials and Methods From 2006 to 2013, 126 non-metastatic NPC patients aged  70 years who were treated with IMRT +/ chemotherapy were included. Adult Comorbidity Evaluation 27 (ACE-27) was used to measure patient comorbidities. The overall survival (OS) and cancer-specific survival (CSS) were calculated with the Kaplan-Meier method, and differences were compared using the log-rank test. The Cox proportional hazards model was used to carry out multivariate analyses. Results For the entire group, only two patients (1.6%) presented stage I disease, and up to 84.1% patients had stage III-IVB disease. All patients had a comorbidity score of 0 in 24 (19.0%), 1 in 45 (35.7%), 2 in 42 (33.3%), and 3 in 15 (11.9%) patients. The main acute grade during radiotherapy was 3-4 adverse events consisting of mucositis (25.4%), bone marrow suppression (16.7%), and dermatitis (8.7%). After treatment, four patients (3.2%) developed temporal lobe injury. Five-year CSS and OS rates were 67.3% (95% confidence interval [CI], 58.6% to 77.4%) and 54.0% (95% CI, 45.6% to 63.9%), respectively. Five-year OS was significantly higher for ACE-27 score 0-1 than ACE-27 score 2-3 (72.9% and 39.9%, respectively; p < 0.001). Multivariate analyses showed ACE-27 score 0-1 was significantly associated with superior OS (hazard ratio [HR], 3.02; 95% CI, 1.64 to 5.55; p < 0.001). In addition, the rate of OS was higher for stage I-III than that of stage IV, with borderline significance (HR, 1.67; 95% CI, 0.99 to 2.82; p=0.053). But no significant advantage was observed in OS when chemotherapy was used (p > 0.05). Conclusion Our findings suggest IMRT +/– chemotherapy has a manageable toxicity and provides an acceptable survival in patients aged  70 years with NPC. ACE-27 score was significantly associated with survival outcomes in this group population.

RNA sequencing reveals that Prx II gene knockout can down-regulate the allograft rejection of dermal mesenchymal stem cells

Han Ying-Hao,Mao Ying-Ying,Yu Nan-Nan,Jin Mei-Hua,Jin Ying-Hua,Wang Ai-Guo,Zhang Yong-Qing,Shen Gui-Nan,Cui Yu-Dong,Yu Li-Yun,Lee Dong-Seok,Jo Yu-Jin,Sun Hu-Nan,Kwon Jeongwoo,권태호 한국응용생명화학회 2020 Applied Biological Chemistry (Appl Biol Chem) Vol.63 No.3

In this study, we used RNA sequencing (RNA-seq) to analyze and compare bulk cell samples from wild-type (WT) dermal mesenchymal stem cells (DMSCs) (n = 3) and Prx II knockout DMSCs (n = 3). The purpose of the study was to elucidate the role of Prx II on allogeneic immune rejection of transplanted DMSCs. The results revealed differential expression of 472 genes (176 up-regulated and 296 down-regulated; p ≤ 0.05) between the PrxII+/+ (WT) and PrxII−/− sample groups. When highly regulated genes were categorized according to the Gene Ontology (GO) molecular function classification and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, the PrxII−/− samples showed a robust downward trend in allograft rejection. The study identified 43 all immunologically rejected differentially expressed genes, of which 41 showed lower expression in the PrxII−/− vs. PrxII+/+ (WT) samples. These findings suggest that Prx II gene knockout may down-regulate the allograft rejection that occurs during DMSCs transplantation and improve the survival rate of DMSCs in the host. This study provides a new perspective on the clinical treatment of stem cell transplantation.

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.

Combination Doxorubicin and Interferon-α Therapy Stimulates Immunogenicity of Murine Pancreatic Cancer Panc02 Cells via Up-regulation of NKG2D ligands and MHC Class I

Wang, Wen-Jia,Qin, Si-Hao,Zhang, Ji-Wei,Jiang, Yue-Yao,Zhang, Jin-Nan,Zhao, Lei Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.22

Background: Pancreatic adenocarcinoma is a malignant gastrointestinal cancer with significant morbidity and mortality. Despite severe side effects of chemotherapy, the use of immunotherapy combined with chemotherapy has emerged as a common clinical treatment. In this study, we investigated the efficacy of the combined doxorubicin and interferon-${\alpha}$ (IFN-${\alpha}$) therapy on murine pancreatic cancer Panc02 cells in vitro and in vivo and underlying mechanisms. Materials and Methods: A Panc02-bearing mouse model was established to determine whether doxorubicin and interferon-${\alpha}$ (IFN-${\alpha}$) could effectively inhibit tumor growth in vivo. Cytotoxicity of natural killer (NK) cells and cytotoxic T lymphocytes (CTLs) was evaluated using a standard LDH release assay. To evaluate the relevance of NK cells and CD8 T cells to the combination therapy-mediated anti-tumor effects, they were depleted in tumor-bearing mice by injecting anti-asialo-GM-1 antibodies or anti-CD8 antibodies, respectively. Finally, the influence of doxorubicin+interferon-${\alpha}$ (IFN-${\alpha}$) on the ligands of NK and T cells was assessed by flow cytometry. Results: The combination therapy group demonstrated a significant inhibition of growth of Panc02 in vivo, resulting from activated cytotoxicity of NK cells and CTLs. Depleting CD8 T cells or NK cells reduced the anticancer effects mediated by immunochemotherapy. Furthermore, the doxorubicin+IFN-a treatment increased the expression of major histocompatibility complex class I (MHC I) and NKG2D ligands on Panc02 cells, suggesting that the combined therapy may be a potential strategy for enhancing immunogenicity of tumors. All these data indicate that the combination therapy using doxorubicin and interferon-${\alpha}$ (IFN-${\alpha}$) may be a potential strategy for treating pancreatic adenocarcinoma.

Growth and Optical Properties of Nanocrystalline/Microcrystalline DiamondMultilayer Films

Jin-Long Luo,Xuan-Tong Ying,Liang-Yao Chen,Pei-Nan Wang 한국물리학회 2005 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.46 No.2

Nanocrystalline/microcrystalline diamond (NCD/MCD) multilayer film with high sp3 bonded carbon concentration and smooth surface has been successfully deposited on silicon substrate. Optimized deposition parameters based on substrate temperature modulation were adopted to grow the NCD/MCD film. The nanocrystallinity, purity and the multilayer structure were characterized by Raman spectroscopy, X-ray diffraction (XRD) and scanning electron microscopy (SEM). The smoothness of the film surface was shown by surface profile measurements and further verified by its high optical transmittance from visible to infrared band. Therefore, this newly proposed NCD/MCD multilayer film would have a variety of optical applications.

Effects of Age, Breast Density and Volume on Breast Cancer Diagnosis: A Retrospective Comparison of Sensitivity of Mammography and Ultrasonography in China's Rural Areas

Wang, Feng-Liang,Chen, Fei,Yin, Hong,Xu, Nan,Wu, Xiao-Xiang,Ma, Jing-Jing,Gao, Shen,Tang, Jin-Hai,Lu, Cheng Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.4

Purpose: Mammography has been confirmed as the only effective mode to improve the prognosis of patients with breast cancer in Western developed countries, but might not be a good choice in other areas of the world. One of the major challenges in China is to determine an optimal imaging modality for breast cancer screening. This study was designed to clarify the sensitivity of ultrasonography compared with that of mammography in rural China. Methods: We retrospectively studied the sensitivity of mammography and ultrasonography based on 306 breast cancer patients detected by the program of "screening for cervical cancer and breast cancer" performed in Chinese rural areas between January 2009 and December 2011, and analyzed the effects of age, breast density and volume on the sensitivity. Results: Stratified analysis showed that the sensitivity of breast ultrasonography was significantly higher than that of mammography in premenopausal patients (81.4% vs. 61.1%, p=0.02), in women ${\leq}$ 55 years of age (82.2% vs. 63.4%, p<0.01), in the high breast density group (American College of Radiology [ACR] levels 3-4) (85.9% vs. 60.6%, p<0.01) and in the small breast volume group (${\leq}$ 400 ml) (87.1% vs. 66.7%, p<0.01). Age had a significant effect on sensitivity of mammography (breast density and volume-adjusted odds ratio, 6.39; 95% confidence interval, 2.8-14.4 in age group > 55 compared to age group ${\leq}$ 45), but not that of ultrasonography. Neither breast density nor volume had significant effect on sensitivity of mammography or ultrasonography. Conclusions: Ultrasonography is more sensitive than mammography in detecting breast cancer in women under 55 year-old Chinese, especially in those with high-density and relatively small breasts.

Human epididymis protein 4 (HE4) protects against cystic pulmonary fibrosis associated‑inflammation through inhibition of NF‑κB and MAPK singnaling

Jinli Wang,Hongyang Zhao,Fenfen Xu,Piaopiao Zhang,Yuan Zheng,Nan Jia 한국유전학회 2019 Genes & Genomics Vol.41 No.9

Background Cystic pulmonary fibrosis (CF) affects mostly the lung of the newborns. Chronic infection and inflammation become the major causes of morbidity and mortality in CF. However, the underlying molecular mechanisms causing CF still remain unclear. Methods ELISA assay was used to examine the expression of HE4 and pro-inflammatory cytokines in W126VA4 cells supernatant fluid. qRT-PCR was applicable to determine the mRNA level of HE4, α-SMA, collagen 1, MMP2, MMP9 and various interleukins. Immunofluorescent assay was used to test the expression of HE4 in WI-26 VA4 cells. Major elements of MAPK and NF-κB signals pathways were examined by western blot. Results We found higher expression of HE4 in CF patients serum and lung biopsy. Interestingly, HE4 expression was positively correlated with fibrosis markers expression. In addition,HE4 overexpression increased inflammatory cytokines secretion and fibrosis markers expression in WI-26 VA4 cells. And NF-κB pathways were responsible for elevated inflammation. In addition, HE4/MAPK/MMPs signaling cascades destroyed the normal extracellular matrix (ECM) and promoted fibrosis. Conclusions Overall, we first identified that HE4 promoted CF-associated inflammation. Additionally, NF-κB and MAPK signalings were further validated to be responsible for CF-associated inflammation and ECM destruction. Characterization of lumacaftor/ivacaftor in CF-associated inflammation may provide a novel insight into clinical CF treatment.