Modulation of Drug Resistance in Ovarian Cancer Cells by Inhibition of Protein Kinase C-alpha (PKC-α) with Small Interference RNA (siRNA) Agents

Zhao, Li-Jun,Xu, Heng,Qu, Jun-Wei,Zhao, Wan-Zhou,Zhao, Yi-Bing,Wang, Jin-Hua Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.8

Objective: To determine whether silence of $PKC-{\alpha}$ expression by small interference RNA (siRNA) might regulate MDR1 expression and reverse chemoresistance of ovarian cancer. Methods: We measured gene and protein expression of MDR1 and $PKC-{\alpha}$ in ovarian cancer cells and assessed their correlation with cell drug resistance. We also examined whether blocking $PKC-{\alpha}$ by RNA interference (RNAi) affected MDR1 expression and reversed drug resistance in drug sensitivity tests. Results: The drug resistance cell lines, OV1228/DDP and OV1228/Taxol, had higher gene and protein expression of MDR1 and $PKC-{\alpha}$ than their counterpart sensitive cell line, OV1228. SiRNA depressed $PKC-{\alpha}$ gene protein expression, as well as MDR1 and protein expression and improved the drug sensitivity in OV1228/DDP and OV1228/Taxol cells. Conclusion: These results indicated that decreasing $PKC-{\alpha}$ expression with siRNA might be an effective method to improve drug sensitivity in drug resistant cells with elevated levels of $PKC-{\alpha}$ and MDR1. A new siRNA-based therapeutic strategy targeting $PKC-{\alpha}$ gene could be designed to overcome the chemoresistance of ovarian cancer.

AT1 Receptor Modulator Attenuates the Hypercholesterolemia-Induced Impairment of the Myocardial Ischemic Post-Conditioning Benefits

Yun-Wei Li,Yan-Ming Li,Yan Hon,Qi-Lin Wan,Rui-Li He,Zhi-Zhong Wang,Cui-Hua Zhao 대한심장학회 2017 Korean Circulation Journal Vol.47 No.2

Background and Objectives: Ischemic post-conditioning (PostC) has been demonstrated as a novel strategy to harness nature’s protection against myocardial ischemia-reperfusion (I/R). Hypercholesterolemia (HC) has been reported to block the effect of PostC on the heart. Angiotensin II type-1 (AT1) modulators have shown benefits in myocardial ischemia. The present study investigates the effect of a novel inhibitor of AT1, azilsartan in PostC of the heart of normocholesterolemic (NC) and HC rats. Materials and Methods: HC was induced by the administration of high-fat diet to the animals for eight weeks. Isolated Langendorff’s perfused NC and HC rat hearts were exposed to global ischemia for 30 min and reperfusion for 120 min. I/R-injury had been assessed by cardiac hemodynamic parameters, myocardial infarct size, release of tumor necrosis factor-alpha troponin I, lactate dehydrogenase, creatine kinase, nitrite in coronary effluent, thiobarbituric acid reactive species, a reduced form of glutathione, superoxide anion, and left ventricle collagen content in normal and HC rat hearts. Results: Azilsartan post-treatment and six episodes of PostC (10 sec each) afforded cardioprotection against I/R-injury in normal rat hearts. PostC protection against I/R-injury was abolished in HC rat hearts. Azilsartan prevented the HC-mediated impairment of the beneficial effects of PostC in I/R-induced myocardial injury, which was inhibited by L-N5-(1-Iminoethyl)ornithinehydrochloride, a potent inhibitor of endothelial nitric oxide synthase (eNOS). Conclusion: Azilsartan treatment has attenuated the HC-induced impairment of beneficial effects of PostC in I/R-injury of rat hearts, by specifically modulating eNOS. Azilsartan may be explored further in I/R-myocardial injury, both in NC and HC conditions, with or without PostC.

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.

The Gender-Sensitive Social Risk Factors for Internet Addiction in College Undergraduate Students

Xia Lin,Jing-yan Gu,Wan-jun Guo,Ya-jing Meng,Hui-yao Wang,Xiao-jing Li,Wei Deng,Lian-sheng Zhao,Xiao-hong Ma,Ming-li Li,Ting Chen,S,K,Cheng,Tao Li 대한신경정신의학회 2021 PSYCHIATRY INVESTIGATION Vol.18 No.7

Objective The current study aims to explore precipitating and social risk factors for internet addiction (IA) in university undergraduate students, and to provide evidence for interventions and the early prevention of IA in different genders. Methods Four thousand eight hundred and fifty-eight college sophomores completed an online survey on their internet use-related behaviours and social risk factors. Results We found that more male (8.3%) than female students (5.4%) had moderate and severe IA. The main online activity in the moderate and severe IA groups was online gaming in males and online streaming in females. Roommates engaging in similar internetbased entertainment was a risk factor of IA only for males, while not being in a romantic relationship was a risk factor of IA for females only. Infatuation with the internet before college and adjustment problems for college life were shared risk factors for both genders in the mild and moderate IA groups. Conclusion IA was a common phenomenon in college students with shared and unique precipitating and social risk factors in males and females. The gender-sensitive risk factors for IA warranted earlier and individualized intervention and prevention strategies for IA in this population.

Sleep Duration and Cancer Risk: a Systematic Review and Meta-analysis of Prospective Studies

Zhao, Hao,Yin, Jie-Yun,Yang, Wan-Shui,Qin, Qin,Li, Ting-Ting,Shi, Yun,Deng, Qin,Wei, Sheng,Liu, Li,Wang, Xin,Nie, Shao-Fa Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.12

To assess the risk of cancers associated with sleep duration using meta-analysis of published cohort studies, we performed a comprehensive search using PubMed, Embase and Web of Science through October 2013. We combined hazard ratios (HRs) from individual studies using meta-analysis approaches. A random effect dose-response analysis was used to evaluate the relationship between sleep duration and cancer risk. Subgroup analyses and sensitivity analyses were also performed. Publication bias was evaluated using Funnel plots and Begg's test. A total of 13 cohorts from 12 studies were included in this meta-analysis, which included 723, 337 participants with 15, 156 reported cancer outcomes during a follow-up period ranging from 7.5 to 22 years. The pooled adjusted HRs were 1.06 (95% CI: 0.92, 1.23; P for heterogeneity =0.003) for short sleep duration, 0.91 (95% CI: 0.78, 1.07; P for heterogeneity <0.0001) for long sleep duration. In subgroup analyses stratified by cancer type, long duration of sleep showed an inverse relation with hormone-related cancer (HR=0.79; 95% CI: 0.65, 0.97; P for heterogeneity =0.009) and a greater risk of colorectal cancer (HR=1.29; 95% CI: 1.09, 1.52; P for heterogeneity =0.346). Further meta-analysis on dose-response relationships showed that the relative risks of cancer were 1.00 (95% CI: 0.99, 1.01; P for linear trend=0.9151) for one hour of sleep increment per day, and 1.00 (95% CI: 0.98, 1.01; P for linear trend=0.7749) for one hour of sleep increment per night. No significant dose-response relationship between sleep duration and cancer was found on non-linearity testing (P=0.5053). Our meta-analysis suggests a positive association between long sleep duration and colorectal cancer, and an inverse association with incidence of hormone related cancers like those in the breast. Studies with larger sample size, longer follow-up times, more cancer types and detailed measure of sleep duration are warranted to confirm these results.

Hypoxia-induced circRNF13 promotes the progression and glycolysis of pancreatic cancer

Zhao Qiuyan,Zhu Zhonglin,Xiao Wenqin,Zong Guanzhao,Wang Chuanyang,Jiang Weiliang,Li Kai,Shen Jie,Guo Xingya,Cui Jianhua,Guo Lihong,Wan Rong 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-

Pancreatic cancer (PC) is one of the most malignant tumors. Rapid progression and distant metastasis are the main causes of patient death. Hypoxia is a hallmark of multiple cancers and is involved in tumor biology. However, little is known about the roles of circRNAs in glycolysis and hypoxia-mediated progression of PC. Here, the expression pattern of hypoxia-related circRNAs was analyzed using RNA sequencing. A unique circRNA termed circRNF13 was found to be upregulated in PC tissues and may be a potential prognostic indicator. HIF-1α and EIF4A3 are involved in regulating the biogenesis of circRNF13. Furthermore, circRNF13 was validated to exert a stimulative effect on cell proliferation, angiogenesis, invasion and glycolysis. Importantly, we found that circRNF13 promoted PDK3 levels by acting as a miR-654-3p sponge, thus promoting the PC malignant process. Collectively, our results reveal that hypoxia-induced circRNF13 mediated by HIF-1α and EIF4A3 promotes tumor progression and glycolysis in PC, indicating the potential of circRNF13 as a prognostic biomarker and therapeutic target for PC.

Transplantation of Wnt5a-modified NSCs promotes tissue repair and locomotor functional recovery after spinal cord injury

Li Xiang,Peng Zhiming,Long Lingli,Lu Xiaofang,Zhu Kai,Tuo Ying,Chen Ningning,Zhao Xiaoyang,Wang Le,Wan Yong 생화학분자생물학회 2020 Experimental and molecular medicine Vol.52 No.-

Traditional therapeutic strategies for spinal cord injury (SCI) are insufficient to repair locomotor function because of the failure of axonal reconnection and neuronal regeneration in the injured central nervous system (CNS). Neural stem cell (NSC) transplantation has been considered a potential strategy and is generally feasible for repairing the neural circuit after SCI; however, the most formidable problem is that the neuronal differentiation rate of NSCs is quite limited. Therefore, it is essential to induce the neuronal differentiation of NSCs and improve the differentiation rate of NSCs in spinal cord repair. Our results demonstrate that both Wnt5a and miRNA200b-3p could promote NSC differentiation into neurons and that Wnt5a upregulated miRNA200b-3p expression through MAPK/JNK signaling to promote NSC differentiation into neurons. Wnt5a could reduce RhoA expression by upregulating miRNA200b-3p expression to inhibit activation of the RhoA/Rock signaling pathway, which has been reported to suppress neuronal differentiation. Overexpression of RhoA abolished the neurogenic capacity of Wnt5a and miRNA200b-3p. In vivo, miRNA200b-3p was critical for Wnt5a-induced NSC differentiation into neurons to promote motor functional and histological recovery after SCI by suppressing RhoA/Rock signaling. These findings provide more insight into SCI and help with the identification of novel treatment strategies.

Design and Characteristic Measurement of 8000 mm Large Aperture Integrating Sphere

Zhao Zhang,Zhi Wan,Xiansheng Li,Hongxing Liu,Jingxu Sun,Zexun Liu,Yamin Wang,Jianwei Ren,Jianyue Ren 한국광학회 2016 Current Optics and Photonics Vol.20 No.4

Integrating spheres play a central role in the radiometric calibration of remote sensors. With thedevelopment of the wide field of view (FOV) remote sensors, aperture diameters of remote sensors arebecoming larger and larger. To satisfy the radiometric calibration requirements of full FOV and fullaperture, an 8000mm diameter large aperture integrating sphere uniform source with a variable exit portwas designed and manufactured. This integrating sphere will be used for pre-launch test and radiometriccalibration of remote satellites. In this paper, optical theories were used to design the output spectralradiance. The LightTools software based on ray-tracing simulation method was used to determine the bestcombination and distribution of inner light sources. A spectral experiment was made to verify the spectralradiance design. To reduce the influence of longtime power-on, a new characteristic measurement methodwas developed to obtain the radiation characteristic of the integrating sphere, which could greatly improvethe measuring efficiency. This method could also be applied to measure other large aperture uniformsources. The obtained results indicate that the spatial uniformity is 98.35%, and the angular uniformityat center position is 98.78%.

Curdione Inhibits Proliferation of MCF-7 Cells by Inducing Apoptosis

Li, Juan,Bian, Wei-He,Wan, Juan,Zhou, Jing,Lin, Yan,Wang, Ji-Rong,Wang, Zhao-Xia,Shen, Qun,Wang, Ke-Ming Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.22

Background: Curdione, one of the major components of Curcuma zedoaria, has been reported to possess various biological activities. It thus might be a candidate anti-flammatory and cancer chemopreventive agent. However, the precise molecular mechanisms of action of curdione on cancer cells are still unclear. In this study, we investigated the effect of curdione on breast cancer. Materials and Methods: Xenograft nude mice were used to detect the effect of curdione on breast cancer in vivo; we also tested the effect of curdione on breast cancer in vitro by MTT, Flow cytometry, JC-I assay, and western blot. Results: Firstly, we found that curdione significantly suppressed tumor growth in a xenograft nude mouse breast tumor model in a dose-dependent manner. In addition, curdione treatment inhibited cell proliferation and induced cell apoptosis. Moreover, after curdione treatment, increase of impaired mitochondrial membrane potential occurred in a concentration dependent manner. Furthermore, the expression of apoptosis-related proteins including cleaved caspase-3, caspase-9 and Bax was increased in curdione treatment groups, while the expression of the anti-apoptotic Bcl-2 was decreased. Inhibitors of caspase-3 were used to confirm that curdione induced apoptosis. Conclusions: Overall, our observations first suggested that curdione inhibited the proliferation of breast cancer cells by inducing apoptosis. These results might provide some molecular basis for the anti-cancer activity of curdione.

Rhizosphere Microbial Community and Metabolites of Susceptible and Resistant Tobacco Cultivars to Bacterial Wilt

Zhao Wan,Li Yanyan,Yang Chunlei,Yang Yong,Hu Yun 한국미생물학회 2023 The journal of microbiology Vol.61 No.4

Soil-borne diseases are closely related to rhizosphere microecosystem. While, plant species and genotypes are important factors affected rhizosphere microecosystem. In this study, the rhizosphere soil microbial community and metabolites of susceptible and resistant tobacco cultivars were investigated. The results showed that there were significant differences in the rhizosphere microbial community and metabolites between susceptible cultivar Yunyan87 and resistant cultivar Fandi3. Furthermore, the rhizosphere soil of Fandi3 showed a higher microbial diversity than that of Yunyan87. The abundance of R. solanacearum was much higher in the rhizosphere soil of Yunyan87 than in the rhizosphere soil of Fandi3, resulting in a higher disease incidence and index. While the abundance of beneficial bacteria in the rhizosphere soil of Fandi3 were higher than that of Yunyan87. Additionally, there were significant differences in metabolites between Yunyan87 and Fandi3 cultivars, and 4-hydroxybenzaldehyde, 3-hydroxy-4-methoxybenzoic acid, vamillic aldehyde, benzoic acid, 4-hydroxybenzyl alcohol, p-hydroxybenzoic acid and phthalic acid were notably high in Yunyan87. Redundancy analysis (RDA) indicated that the rhizosphere microbial community of Fandi3 and Yunyan87 were highly correlated with various environmental factors and metabolites. Overall, susceptible and resistant tobacco cultivars had different impact on rhizosphere microbial community and metabolites. The results expand our understanding of the roles of tobacco cultivars in plant-micro-ecosystem interactions, and provide a basis for the control of tobacco bacterial wilt.