Site-directed Mutagenesis of the Toxin from the Chinese Scorpion Buthus martensii Karsch (BmKAS): Insight into Sites Related to Analgesic Activity

Yong Cui,Yong-Bo Song,Lin Ma,Yan-Feng Liu,Guo-Dong Li,Chun-Fu Wu,Jing-Hai Zhang 대한약학회 2010 Archives of Pharmacal Research Vol.33 No.10

This study utilized the E. coli expression system to investigate the role of amino acid residues in toxin from the Chinese scorpion - Buthus martensii Karsch (BmKAS). To evaluate the extent to which residues of the toxin core contribute to its analgesic activity, ten mutants of BmKAS were obtained by PCR. Using site-directed mutagenesis, all of these residues were substituted with different amino acids. This study represents a thorough mapping and elucidation of the epitopes that form the molecular basis of the toxin’s analgesic activity. Our results showed large mutant-dependent differences that emphasize the important roles of the studied residues.

The AURKA Gene rs2273535 Polymorphism Contributes to Breast Carcinoma Risk - Meta-analysis of Eleven Studies

Guo, Xu-Guang,Zheng, Lei,Feng, Wei-Bo,Xia, Yong Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.16

The rs2273535 polymorphism in the AURKA gene had proven to be associated with breast carcinoma susceptibility. Nevertheless, the results of different studies remain contradictory. A meta-analysis covering 28, 789 subjects from eleven different studies was here carried out in order to investigate the association in detail. The random effects model was used to analyze the pooled odds ratios (ORs) and their corresponding 95% confidence intervals (95% CIs). A significant relationship between the rs2273535 polymorphism and breast tumors was found in an allelic genetic model (OR: 1.076, 95% CI: 1.004-1.153, p=0.040, $P_{heterogeneity}$=0.002). No significant association was detected in a homozygote model (OR: 1.186, 95% CI: 0.990-1.423, P=0.065, $P_{heterogeneity}$=0.002), a heterozygote model (OR: 1.016, 95% CI: 0.959-1.076, p=0.064, $P_{heterogeneity}$=0.000), a dominant genetic model (OR: 1.147, 95% CI: 0.992-1.325, p=0.217, $P_{heterogeneity}$=0.294) and a recessive genetic model (OR: 1.093, 95% CI: 0.878-1.361, p=0.425, $P_{heterogeneity}$=0.707). A significant relationship between the rs2273535 polymorphism in the AURKA gene and breast tumor in Asian group was found in an allelic genetic model (OR: 1.124, 95% CI: 1.003-1.29, p=0.044, $P_{heterogeneity}$=0.034), a homozygote model (OR: 1.229, 95% CI: 1.038-1.455, p=0.016, $P_{heterogeneity}$=0.266) and a recessive genetic model (OR: 1.227, 95% CI: 1.001-1.504, p=0.049, $P_{heterogeneity}$=0.006). A significant association was thus observed between the rs2273535 polymorphism in the AURKA gene and breast cancer risk. Individuals with the rs2273535 polymorphism in the AURKA gene have a higher risk of breast cancer in Asian populations, but not in Caucasians.

Variation of Urinary and Serum Trace Elements (Ca, Zn, Cu, Se) in Bladder Carcinoma in China

Guo, Kun-Feng,Zhang, Zhe,Wang, Jun-Yong,Gao, Sheng-Lin,Liu, Jiao,Zhan, Bo,Chen, Zhi-Peng,Kong, Chui-Ze Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.5

Backgrounds: Deficiency or excess of trace elements can induce body metabolic disorders and cellular growth disturbance, even mutation and cancerization. Since there are few studies of the effect of trace elements in bladder carcinoma in China, the aim of this study was thus to assess variation using a case control approach. Methods: To determine this, 81 patients with bladder carcinoma chosen as a study group and 130 healthy persons chosen as a control group were all assayed for urinary and serum trace elements (calcium [Ca], zinc [Zn], copper [Cu], selenium [Se]) using an atomic absorption spectrophotometer, and the results were analyzed by independent sample t tests. The correlative factors on questionnaires answered by all persons were analyzed by logistic regression. Results: The results showed urinary Ca, Zn and serum Cu levels of the study group to be significantly higher (P<0.05) than those of he control group. Serum Ca and Se levels of study group were significantly lower (P<0.05) than those of control group. Conclusion: There were higher urinary Zn and serum Cu concentrations in bladder carcinoma cases. Bladder carcinoma may be associated with Ca metabolic disorder, leading to higher urinary Ca and lower serum Ca. Low serum Se and smoking appear to be other risk factors for bladder carcinoma in China.

Identification of Specific Gene Modules in Mouse Lung Tissue Exposed to Cigarette Smoke

Xing, Yong-Hua,Zhang, Jun-Ling,Lu, Lu,Li, De-Guan,Wang, Yue-Ying,Huang, Song,Li, Cheng-Cheng,Zhang, Zhu-Bo,Li, Jian-Guo,Xu, Guo-Shun,Meng, Ai-Min Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.10

Background: Exposure to cigarette may affect human health and increase risk of a wide range of diseases including pulmonary diseases, such as chronic obstructive pulmonary disease (COPD), asthma, lung fibrosis and lung cancer. However, the molecular mechanisms of pathogenesis induced by cigarettes still remain obscure even with extensive studies. With systemic view, we attempted to identify the specific gene modules that might relate to injury caused by cigarette smoke and identify hub genes for potential therapeutic targets or biomarkers from specific gene modules. Materials and Methods: The dataset GSE18344 was downloaded from the Gene Expression Omnibus (GEO) and divided into mouse cigarette smoke exposure and control groups. Subsequently, weighted gene co-expression network analysis (WGCNA) was used to construct a gene co-expression network for each group and detected specific gene modules of cigarette smoke exposure by comparison. Results: A total of ten specific gene modules were identified only in the cigarette smoke exposure group but not in the control group. Seven hub genes were identified as well, including Fip1l1, Anp32a, Acsl4, Evl, Sdc1, Arap3 and Cd52. Conclusions: Specific gene modules may provide better understanding of molecular mechanisms, and hub genes are potential candidates of therapeutic targets that may possible improve development of novel treatment approaches.

Selective Radiotherapy after Distant Metastasis of Nasopharyngeal Carcinoma Treated with Dose-Dense Cisplatin plus Fluorouracil

Liang, Yong,Bu, Jun-Guo,Cheng, Jin-ling,Gao, Wei-Wei,Xu, Yao-Can,Feng, Jian,Chen, Bo-Yu,Liang, Wei-Chao,Chen, Ke-Quan Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.14

Purpose: To investigate the efficacy and safety of selective radiotherapy after distant metastasis of nasopharyngeal carcinoma (NPC) treated with dose-dense cisplatin plus fluorouracil. Materials and Methods: Eligible patients were randomly assigned to a study group treated with dose-dense cisplatin plus fluorouracil following selective radiotherapy and a control group receiving traditional cisplatin plus fluorouracil following selective radiotherapy according to a 1:1 distribution using a digital random table method. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS), objective response rate, relapse or progression rate in the radiation field and treatment toxicity. Results: Of 52 patients in the study group, 20 cases underwent radiotherapy., while in the control group of 51 patients, 16 underwent radiotherapy. The median PFS, median OS, survival rates in 1, 2 and 3 years in study and control group were 20.9 vs 12.7months, 28.3 vs 18.8months, 85.2%vs 65.9%, 62.2% vs 18.3%, and 36.6%vs 5.2% (p values of 0.00, 0.00, 0.04, 0.00 and 0.00, respectively). Subgroup analysis showed that the median OS and survival rates of 1, 2, 3 years for patients undergoing radiotherapy in the study group better than that in control group( 43.2vs24.1 months, 94.1% vs 86.7%, 82.4% vs 43.3%, 64.7% vs 17.3%, (p=0.00, 0.57, 0.04 and 0.01, respectively). The complete response rate, objective response rate after chemotherapy and three months after radiotherapy, relapse or progression rate in radiation field in study group and in control group were 19.2% vs 3.9%, 86.5% vs 56.9%, 85% vs 50%, 95% vs 81.3% and 41.3% vs 66.7% (p =0.03, 0.00, 0.03,0.30, 0.01 respectively). The grade 3-4 acute adverse reactions in the study group were significantly higher than in the control group (53.8% vs 9.8%, p=0.00). Conclusions: The survival of patients benefits from selective radiotherapy after distant metastasis of NPC treated with dose-dense cisplatin plus fluorouracil.

Hydraulic fracture initiation pressure of anisotropic shale gas reservoirs

Zhu, Haiyan,Guo, Jianchun,Zhao, Xing,Lu, Qianli,Luo, Bo,Feng, Yong-Cun Techno-Press 2014 Geomechanics & engineering Vol.7 No.4

Shale gas formations exhibit strong mechanical and strength anisotropies. Thus, it is necessary to study the effect of anisotropy on the hydraulic fracture initiation pressure. The calculation model for the in-situ stress of the bedding formation is improved according to the effective stress theory. An analytical model of the stresses around wellbore in shale gas reservoirs, in consideration of stratum dip direction, dip angle, and in-situ stress azimuth, has been built. Besides, this work established a calculation model for the stress around the perforation holes. In combination with the tensile failure criterion, a prediction model for the hydraulic fracture initiation pressure in the shale gas reservoirs is put forward. The error between the prediction result and the measured value for the shale gas reservoir in the southern Sichuan Province is only 3.5%. Specifically, effects of factors including elasticity modulus, Poisson's ratio, in-situ stress ratio, tensile strength, perforation angle (the angle between perforation direction and the maximum principal stress) of anisotropic formations on hydraulic fracture initiation pressure have been investigated. The perforation angle has the largest effect on the fracture initiation pressure, followed by the in-situ stress ratio, ratio of tensile strength to pore pressure, and the anisotropy ratio of elasticity moduli as the last. The effect of the anisotropy ratio of the Poisson's ratio on the fracture initiation pressure can be ignored. This study provides a reference for the hydraulic fracturing design in shale gas wells.

Field monitoring of splitting failure for surrounding rock masses and applications of energy dissipation model

Wang, Zhi-shen,Li, Yong,Zhu, Wei-shen,Xue, Yi-guo,Jiang, Bei,Sun, Yan-bo Techno-Press 2017 Geomechanics & engineering Vol.12 No.4

Due to high in-situ stress and brittleness of rock mass, the surrounding rock masses of underground caverns are prone to appear splitting failure. In this paper, a kind of loading-unloading variable elastic modulus model has been initially proposed and developed based on energy dissipation principle, and the stress state of elements has been determined by a splitting failure criterion. Then the underground caverns of Dagangshan hydropower station is analyzed using the above model. For comparing with the monitoring results, the entire process of rock splitting failure has been achieved through monitoring the splitting failure on side walls of large-scale caverns in Dagangshan via borehole TV, micro-meter and deformation resistivity instrument. It shows that the maximum depth of splitting area in the downstream sidewall of the main power house is approximately 14 m, which is close to the numerical results, about 12.5 m based on the energy dissipation model. As monitoring result, the calculation indicates that the key point displacement of caverns decreases firstly with the distance from main powerhouse downstream side wall rising, and then increases, because this area gets close to the side wall of main transformer house and another smaller splitting zone formed here. Therefore it is concluded that the energy dissipation model can preferably present deformation and fracture zones in engineering, and be very useful for similar projects.

Intensity-Modulated Radiotherapy versus Three-Dimensional Conformal Radiotherapy in Definitive Chemoradiotherapy for Cervical Esophageal Squamous Cell Carcinoma: Comparison of Survival Outcomes and Toxicities

Nai-Bin Chen,Bo Qiu,Jun Zhang,Meng-Yun Qiang,Yu-Jia Zhu,Bin Wang,Jin-Yu Guo,Ling-Zhi Cai,Shao-Min Huang,Meng-Zhong Liu,Qun Li,Yong-Hong Hu,Qi-Wen Li,Hui Liu 대한암학회 2020 Cancer Research and Treatment Vol.52 No.1

Purpose The purpose of this study was to compare the survival and toxicities in cervical esophageal squamous cell carcinoma (CESCC) treated by concurrent chemoradiothrapy with either three-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT) techniques. Materials and Methods A total of 112 consecutive CESCC patients were retrospectively reviewed. 3D-CRT and IMRT groups had been analyzed by propensity score matching method, with sex, age, Karnofsky performance status, induction chemotherapy, and tumor stage well matched. The Kaplan- Meier method and Cox proportional hazards model were used for overall survival (OS) and progression-free survival (PFS). Toxicities were compared between two groups by Fisher exact test. Results With a median follow-up time of 34.9 months, the 3-year OS (p=0.927) and PFS (p=0.859) rate was 49.6% and 45.8% in 3D-CRT group, compared with 54.4% and 42.8% in IMRT group. The rates of grade ! 3 esophagitis, grade ! 2 pneumonitis, esophageal stricture, and hemorrhage were comparable between two groups, while the rate of tracheostomy dependence was much higher in IMRT group than 3D-CRT group (14.3% vs.1.8%, p=0.032). Radiotherapy technique (hazard ratio [HR], 0.09; 95% confidence interval [CI], 0.01 to 0.79) and pretreatment hoarseness (HR, 0.12; 95% CI 0.02 to 0.70) were independently prognostic of tracheostomy dependence. Conclusion No survival benefits had been observed while comparing IMRT versus 3D-CRT in CESCC patients. IMRT with fraction dose escalation and pretreatment hoarseness were considered to be associated with a higher risk for tracheostomy dependence. Radiation dose escalation beyond 60 Gy should be taken into account carefully when using IMRT with hypofractionated regimen.

Two new benzylisoquinoline alkaloids from Thalictrum foliolosum and their antioxidant and in vitro antiproliferative properties

Da-Hong Li,Jia Guo,Wen Bin,Nan Zhao,Kai-bo Wang,Jian-yong Li,Zhan-Lin Li,Hui-Ming Hua 대한약학회 2016 Archives of Pharmacal Research Vol.39 No.7

Two novel rare chloro-containing benzylisoquinolinealkaloids, thalfoliolosumines A (1) and B (2),along with eight known isoquinoline alkaloids (3–10) wereisolated from the whole plant of Thalictrum foliolosum. The structures of these compounds were elucidated byspectral analyses, including 1D and 2D NMR (COSY,HSQC, HMBC and NOESY) experiments. The antiproliferativeeffects of all the isolated compounds were evaluatedby MTT method against MCF-7, PC-3, and U937cells, and trypan blue method against HL-60 cells. Newcompounds 1 and 2 exhibited moderate in vitro antiproliferativeactivity against MCF-7, PC-3, and HL-60 cells,and good inhibitory effects against U937 cells with IC50values of 7.50 and 6.97 μM, respectively. Compounds 7and 10 showed the strongest in vitro antiproliferative withIC50 values of 0.93 and 1.69 lM against HL-60 cell line. The antioxidant properties were also measured, bisbenzyltetrahydroisoquinolinealkaloids 3–6 showed the strongestantioxidant activities in ABTS assay.

Preparation and investigation of hydrolyzed polyacrylonitrile as a preliminary biomedical hydrogel

Ji Hoon Park,Guo Zhe Tai,Bo Keun Lee,Seung Hun Park,Ja Yong Jang,Jung Soo Lee,Jae Ho Kim,Kwideok Park,장주웅,김문석 한국생체재료학회 2015 생체재료학회지 Vol.19 No.4

Background: Hydrolyzed polyacrylonitrile (HPAN) has attracted much attention as a hydrogel for a broad range of biomedical applications. Therefore, in this study, we prepared HPAN derivatives with controllable compositions by the radical polymerization of acrylonitrile (AN), methacrylic acid (MAA) and N-isopropylacrylamide (NIPAM) monomers. Results: The prepared poly(AN-co-MAA-co-NIPAM) copolymers had different ratios of AN, MAA, and NIPAM and molecular weights ranging from 2000 to 50,000. The copolymers were prepared as films to examine their properties. The prepared copolymer films showed different solubilities, contact angles, and swelling ratios. The properties of the copolymer films were affected by the hydrophobic PAN segments and the hydrophilic PMAA or PNIPAM segments. Conclusion: Thus, we conclude that introducing PMAA and PNIPAM segments with different ratios and lengths into PAN segments could represent a method of controlling the hydrogel properties of copolymers.