Human lactoferrin efficiently targeted into caprine beta-lactoglobulin locus with transcription activator-like effector nucleases

Yu-Guo Yuan,Shao-Zheng Song,Meng-Ming Zhu,Zheng-Yi He,Rui Lu,Ting Zhang,Fei Mi,Jin-Yu Wang,Yong Cheng 아세아·태평양축산학회 2017 Animal Bioscience Vol.30 No.8

Objective: To create genetically modified goat as a biopharming source of recombinant human lacotoferrin (hLF) with transcription activator-like effector nucleases. Methods: TALENs and targeting vector were transferred into cultured fibroblasts to insert hLF cDNA in the goat beta-lactoglobulin (BLG) locus with homology-directed repair. The gene targeted efficiency was checked using sequencing and TE7I assay. The bi-allelic gene targeted colonies were isolated and confirmed with polymerase chain reaction, and used as donor cells for somatic cell nuclear transfer (SCNT). Results: The targeted efficiency for BLG gene was approximately 10%. Among 12 Bi-allelic gene targeted colonies, five were used in first round SCNT and 4 recipients (23%) were confirmed pregnant at 30 d. In second round SCNT, 7 (53%), 4 (31%), and 3 (23%) recipients were confirmed to be pregnant by ultrasound on 30 d, 60 d, and 90 d. Conclusion: This finding signifies the combined use of TALENs and SCNT can generate bi-allelic knock-in fibroblasts that can be cloned in a fetus. Therefore, it might lay the foundation for transgenic hLF goat generation and possible use of their mammary gland as a bioreactor for large-scale production of recombinant hLF.

Modelling of the Hot Flow Behaviors for Ti-13Nb-13Zr Alloy by BP-ANN Model and Its Application

Guo-zheng Quan,Shi-ao Pu,Zong-yang Zhan,Zhen-yu Zou,Ying-ying Liu,Yu-feng Xia 한국정밀공학회 2015 International Journal of Precision Engineering and Vol. No.

The plastic deformation mechanisms and the constitutive model of flow behaviors at different deformation conditions in biomedical titanium alloy are an essential step to optimize the design of any forging process for implant productions. A series of isothermal compressions tests on Ti-13Nb-13Zr alloy in a wide range of true strain, temperature and strain rate were conducted on a thermomechanical simulator. The hot flow behaviors with different softening mechanisms, including dynamic recrystallization and dynamic recovery, were characterized based on true strain-stress curves. A back-propagational artificial neural network (BP-ANN) method was conducted to evaluate and predict this non-linear problem by self-training to be adaptable to the material characteristics. The flow stress of this material a wide deformation condition range can be predicted accurately by the BP-ANN model obtained in this study. The prediction ability of this BP-ANN Model was evaluated by three accuracy indexes, Absolute error, Relative error and Average absolute relative error. Sequently, the developed BP-ANN model was programed and implanted into the finite element (FE) analysis platform, Msc.Marc software. The results have sufficiently articulated that the well-trained ANN model has excellent capability to deal with the complex flow behaviors and has great application potentiality in hot deformation processes.

A Prediction Model Based on the Risk Factors Associated with Pathological Upgrading in Patients with Early-Stage Gastric Neoplasms Diagnosed by Endoscopic Forceps Biopsy

Zhao Yu Han,Zheng Yu,Sha Jie,Hua Hong Jin,Li Ke Dong,Lu Yu,Dang Yi Ni,Zhang Guo Xin 거트앤리버 소화기연관학회협의회 2023 Gut and Liver Vol.17 No.1

Background/Aims: The discrepancies between the diagnosis of preoperative endoscopic forceps biopsy (EFB) and endoscopic submucosal dissection (ESD) in patients with early gastric neoplasm (EGN) exist objectively. Among them, pathological upgrading directly influences the accuracy and appropriateness of clinical decisions. The aims of this study were to investigate the risk factors for the discrepancies, with a particular focus on pathological upgrading and to establish a prediction model for estimating the risk of pathological upgrading after EFB. Methods: We retrospectively collected the records of 978 patients who underwent ESD from December 1, 2017 to July 31, 2021 and who had a final histopathology determination of EGN. A nomogram to predict the risk of pathological upgrading was constructed after analyzing subgroup differences among the 901 lesions enrolled. Results: The ratio of pathological upgrading was 510 of 953 (53.5%). Clinical, laboratorial and endoscopic characteristics were analyzed using univariable and binary multivariable logistic regression analyses. A nomogram was constructed by including age, history of chronic atrophic gastritis, symptoms of digestive system, blood high density lipoprotein concentration, macroscopic type, pathological diagnosis of EFB, uneven surface, remarkable redness, and lesion size. The C-statistics were 0.804 (95% confidence interval, 0.774 to 0.834) and 0.748 (95% confidence interval, 0.664 to 0.832) in the training and validation set, respectively. We also built an online webserver based on the proposed nomogram for convenient clinical use. Conclusions: The clinical value of identifying the preoperative diagnosis of EGN lesions is limited when using EFB separately. We have developed a nomogram that can predict the probability of pathological upgrading with good calibration and discrimination value.

Comparison of Liver Transplantation and Liver Resection for Hepatocellular Carcinoma Patients with Portal Vein Tumor Thrombus Type I and Type II

Jia-Yu Lv,Ning-Ning Zhang,Ya-Wei Du,Ying Wu,Tian-Qiang Song,Ya-Min Zhang,Yan Qu,Yu-Xin Liu,Jie Gu,Ze-Yu Wang,Yi-Bo Qiu,Bing Yang,Da-Zhi Tian,Qing-Jun Guo,Li Zhang,Ji-San Sun,Yan Xie,Zheng-Lu Wang,Xin 연세대학교의과대학 2021 Yonsei medical journal Vol.62 No.1

Purpose: The aim of this study was to compare the efficacy of liver transplantation (LT) and liver resection (LR) for hepatocellularcarcinoma (HCC) patients with portal vein tumor thrombus (PVTT) and to investigate risk factors affecting prognosis. Materials and Methods: A total of 94 HCC patients with PVTT type I (segmental PVTT) and PVTT type II (lobar PVTT) were involvedand divided into LR (n=47) and LT groups (n=47). Recurrence-free survival (RFS) and overall survival (OS) were comparedbefore and after inverse probability of treatment weighting (IPTW). Prognostic factors for RFS and OS were explored. Results: Two treatment groups were well-balanced using IPTW. In the entire cohort, LT provided a better prognosis than LR. Among patients with PVTT type I, RFS was better with LT (p=0.039); OS was not different significantly between LT and LR(p=0.093). In subgroup analysis of PVTT type I patients with α-fetoprotein (AFP) levels >200 ng/mL, LT elicited significantly longermedian RFS (18.0 months vs. 2.1 months, p=0.022) and relatively longer median OS time (23.6 months vs. 9.8 months, p=0.065). Among patients with PVTT type II, no significant differences in RFS and OS were found between LT and LR (p=0.115 and 0.335,respectively). Multivariate analyses showed treatment allocation (LR), tumor size (>5 cm), AFP and aspartate aminotransferase(AST) levels to be risk factors of RFS and treatment allocation (LR), AFP and AST as risk factors for OS. Conclusion: LT appeared to afford a better prognosis for HCC with PVTT type I than LR, especially in patients with AFP levels>200 ng/mL.

BRCA1 Gene Exon 11 Mutations in Uighur and Han Women with Early-onset Sporadic Breast Cancer in the Northwest Region of China

Cao, Yu-Wen,Fu, Xin-Ge,Wan, Guo-Xing,Yu, Shi-Ying,Cui, Xiao-Bin,Li, Li,Jiang, Jin-Fang,Zheng, Yu-Qin,Zhang, Wen-Jie,Li, Feng Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.11

The prevalence of BRCA1 gene mutations in breast cancer differs between diverse ethnic groups. Relatively little information is known about patterns of BRCA1 mutations in early-onset breast cancer in women of Uighur or Han descent, the major ethnic populations of the Xinjiang region in China. The aim of this study was to identify BRCA1 mutations in Uighur and Han patients with early-onset (age <35 years), and sporadic breast cancer for genetic predisposition to breast cancer. For detection of BRCA1 mutations, we used a polymerase chain reaction single-stranded conformation polymorphism approach, followed by direct DNA sequencing in 22 Uighur and 13 Han women with early-onset sporadic breast cancer, and 32 women with benign breast diseases. The prevalence of BRCA1 mutations in this population was 22.9% (8/35) among early-onset sporadic breast cancer cases. Of these, 31.8% (7/22) of Uighur patients and 7.69% (1/13) of Han patients were found to have BRCA1 mutations. In 7 Uighur patients with BRCA1 mutations, there were 11 unique sequence alterations in the BRCA1 gene, including 4 clearly disease-associated mutations on exon 11 and 3 variants of uncertain clinical significance on exon 11, meanwhile 4 neutral variants on intron 20 or 2. None of the 11 BRCA1 mutations identified have been previously reported in the Breast Cancer Information Core database. These findings reflect the prevalence of BRCA1 mutations in Uighur women with early-onset and sporadic breast cancer, which will allow for provision of appropriate genetic counseling and treatment for Uighur patients in the Xinjiang region.

Carnosic acid protects against acetaminophen-induced hepatotoxicity by potentiating Nrf2-mediated antioxidant capacity in mice

Guo, Qi,Shen, Zhiyang,Yu, Hongxia,Lu, Gaofeng,Yu, Yong,Liu, Xia,Zheng, Pengyuan The Korean Society of Pharmacology 2016 The Korean Journal of Physiology & Pharmacology Vol.20 No.1

Acetaminophen (APAP) overdose is one of the most common causes of acute liver failure. The study aimed to investigate the protective effect of carnosic acid (CA) on APAP-induced acute hepatotoxicity and its underlying mechanism in mice. To induce hepatotoxicity, APAP solution (400 mg/kg) was administered into mice by intraperitoneal injection. Histological analysis revealed that CA treatment significantly ameliorated APAP-induced hepatic necrosis. The levels of both alanine aminotransferase (ALT) and aspartate transaminase (AST) in serum were reduced by CA treatment. Moreover, CA treatment significantly inhibited APAP-induced hepatocytes necrosis and lactate dehydrogenase (LDH) releasing. Western blot analysis showed that CA abrogated APAP-induced cleaved caspase-3, Bax and phosphorylated JNK protein expression. Further results showed that CA treatment markedly inhibited APAP-induced pro-inflammatory cytokines TNF-${\alpha}$, IL-$1{\beta}$, IL-6 and MCP-1 mRNA expression and the levels of phosphorylated $I{\kappa}B{\alpha}$ and p65 protein in the liver. In addition, CA treatment reduced APAP- induced hepatic malondialdehyde (MDA) contents and reactive oxygen species (ROS) accumulation. Conversely, hepatic glutathione (GSH) level was increased by administration of CA in APAP-treated mice. Mechanistically, CA facilitated Nrf2 translocation into nuclear through blocking the interaction between Nrf2 and Keap1, which, in turn, upregulated anti-oxidant genes mRNA expression. Taken together, our results indicate that CA facilitates Nrf2 nuclear translocation, causing induction of Nrf2-dependent genes, which contributes to protection from acetaminophen hepatotoxicity.

Nicotine exacerbates tacrolimus-induced renal injury by programmed cell death

( Yu Ji Jiang ),( Sheng Cui ),( Kang Luo ),( Jun Ding ),( Qi Yan Nan ),( Shang Guo Piao ),( Mei Ying Xuan ),( Hai Lan Zheng ),( Yong Jie Jin ),( Ji Zhe Jin ),( Jung Pyo Lee ),( Byung Ha Chung ),( Bum 대한내과학회 2021 The Korean Journal of Internal Medicine Vol.36 No.6

Background/Aims: Cigarette smoking is an important modifiable risk factor in kidney disease progression. However, the underlying mechanisms for this are lacking. This study aimed to assess whether nicotine (NIC), a major toxic component of cigarette smoking, would exacerbates tacrolimus (TAC)-induced renal in-jury. Methods: Sprague-Dawley rats were treated daily with NIC, TAC, or both drugs for 4 weeks. The influence of NIC on TAC-caused renal injury was examined via renal function, histopathology, oxidative stress, mitochondria, endoplasmic reticulum (ER) stress, and programmed cell death (apoptosis and autophagy). Results: Both NIC and TAC significantly impaired renal function and histopathology, while combined NIC and TAC treatment aggravated these parameters beyond the effects of either alone. Increased oxidative stress, ER stress, mitochondrial dysfunction, proinflammatory and profibrotic cytokine expressions, and programmed cell death from either NIC or TAC were also aggravated by the two combined. Conclusions: Our observations suggest that NIC exacerbates chronic TAC nephrotoxicity, implying that smoking cessation may be beneficial for transplant smokers taking TAC.

Back-analysis by UDEC of the Failure Process of Wangjiayan Co-seismic Landslide during 2008.5.12 Wenchuan Earthquake.

( Yu Zou ),( Shengwen Qi ),( Songfeng Guo ),( Zhifa Zhan ),( Xiaolin Huang ),( Bowen Zheng ),( Ning Liang ),( Jiaguo Xia ),( Xingxing Li ) 대한지질공학회 2019 대한지질공학회 학술발표회논문집 Vol.2019 No.2

Strong earthquakes such as the 2008 Wenchuan earthquake often induced numerous landslides, which resulted in a large number of casualties and property losses. Under a strong earthquake, a rock slope often produced a dynamic progressive failure. Understanding the process of the dynamic progressive failure of the rock slope is of great significance for the prediction and prevention of the co-seismic landslide. Generally, the numerical method is a feasible and economic alternative to solve this problem. However, previous studies presumed the failure surface and area in the numerical model, which cannot reproduce the dynamic progressive failure of the rock slope. In this paper, we applied the Universal Discrete Element method (UDEC) was adopted to quantitatively characterize the dynamic progressive failure process of the Wangjiayan co-seismic landslide triggered by 2008 Wenchan earthquake. Different from previous studies, there exists no presumed failure surface and area was was presumed in the UDEC model. The initiation, coalescence of the local fractures and the formation of the final failure surface were well simulated in a real-time way. Some key factors influencing the dynamic progressive failure of the rock slope were systematically explored. This study provided a new insight to understand the disaster-pregnant mechanism, evolution, and formation of the co-seismic landslide.

Multi-Variable and Bi-Objective Optimization of Electric Upsetting Process for Grain Refinement and Its Uniform Distribution

Guo-zheng Quan,Le Zhang,Chao An,Zhen-yu Zou 한국정밀공학회 2018 International Journal of Precision Engineering and Vol.19 No.6

It is significant to adjust the microstructures of preforms in pursuit of high-quality exhaust valves. This work is a novel attempt to identify the optimum process parameters in electric upsetting of 3Cr20Ni10W2 high-alloy to achieve grain refinement and uniform distribution by multi-objective genetic algorithm (MOGA) optimization. A finite element (FE) model on basis of electric-thermalmechanical and macro-micro sequential multi-physics analysis methods was developed in software MSC. Mar. And different schedules of four independent process variables (heating current (I), clamping length (L), upsetting pressure (Pset) and velocity of the anvil cylinder (v)) were performed aiming to achieve two objective indicators (average grain size (dav) and inhomogeneous degree of grain distribution (σd)). Then, two objective response surfaces were constructed as the functions between the two indicators and the four independent process variables. As per the criterion that simultaneously minimize dav and σd, the processing parameters (Pset, L, v, I) were optimized by MOGA, and corresponding numerical simulation were performed. The results show that both dav and σd are improved significantly at the optimal process condition as verified by the trial-manufacture experiments, which validated the optimal design and corresponding simulation based on grain refinement and uniform distribution by MOGA was credible and effective.

Concomitant EGFR Inhibitors Combined with Radiation for Treatment of Non-small Cell Lung Carcinoma

Zheng, De-Jie,Yu, Guo-Hua,Gao, Jian-Feng,Gu, Jun-Dong Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.8

Epidermal growth factor receptor (EGFR) is considered to be one of the key driver genes in non-small cell lung cancer (NSCLC). Several clinical trials have shown great promise of EGFR tyrosine kinase inhibitors (TKIs) in the first-line treatment of NSCLC. Many advances have been made in the understanding of EGFR signal transduction network and the interaction between EGFR and tumor microenvironment in mediating cancer survival and development. The concomitant targeted therapy and radiation is a new strategy in the treatment of NSCLC. A number of preclinical studies have demonstrated synergistic anti-tumor activity in the combination of EGFR inhibitors and radiotherapy in vitro and in vivo. In the present review, we discuss the rationale of the combination of EGFR inhibitors and radiotherapy in the treatment of NSCLC.