Targeting treatment of bladder cancer using PTK7 aptamer-gemcitabine conjugate

Xiang Wei,Peng Yongbo,Zeng Hongliang,Yu Chunping,Zhang Qun,Liu Biao,Liu Jiahao,Hu Xing,Wei Wensu,Deng Minhua,Wang Ning,Liu Xuewen,Xie Jianfei,Hou Weibin,Tang Jin,Long Zhi,Wang Long,Liu Jianye 한국생체재료학회 2023 생체재료학회지 Vol.27 No.00

Gemcitabine (GEM) is one of the first-line chemotherapies for bladder cancer (BC), but the GEMs cannot recognize cancer cells and have a low long-term response rate and high recurrence rate with side effects during the treatment of BC. Targeted transport of GEMs to mediate cytotoxicity to tumor and avoid the systemic side effects remains a challenge in the treatment of BC.Based on a firstly confirmed biomarker in BC-protein tyrosine kinase 7 (PTK7), which is overexpressed on the cell membrane surface in BC cells, a novel targeting system protein tyrosine kinase 7 aptamer-Gemcitabine conjugate (PTK7-GEMs) was designed and synthesized using a specific PTK7 aptamer and GEM through auto-synthesis method to deliver GEM against BC. In addition, the antitumor effects and safety evaluation of PTK7-GEMs was assessed with a series of in vitro and in vivo assays.PTK7-GEMs can specifically bind and enter to BC cells dependent on the expression levels of PTK7 and via the macropinocytosis pathway, which induced cytotoxicity after GEM cleavage from PTK7-GEMs respond to the intracellular phosphatase. Moreover, PTK7-GEMs showed stronger anti-tumor efficacy and excellent biosafety in three types of tumor xenograft mice models.These results demonstrated that PTK7-GEMs is a successful targeted aptamer-drug conjugates strategy (APDCs) to treat BC, which will provide new directions for the precision treatment of BC in the field of biomarker-oriented tumor targeted therapy.

Adaptive Unscented Kalman Filter Based Estimation and Filtering for Dynamic Positioning with Model Uncertainties

Fang Deng,Hua-Lin Yang,Long-Jin Wang 제어·로봇·시스템학회 2019 International Journal of Control, Automation, and Vol.17 No.3

A novel adaptive unscented Kalman filter (AUKF) is presented and applied to ship dynamic positioning(DP) system with model uncertainties of time-varying noise statistics, model mismatch and slow varying driftforces. The adaptive algorithm is proposed to simultaneously online adapt the process and measurement noisecovariance by adopting the main principle of covariance matching. The measurement noise covariance is adaptedbased on residual covariance matching method, and then the process noise covariance is adjusted by using adaptivescaling factor. Simulation comparisons among the proposed RQAUKF, the strong tracking UKF (RSTAUKF) andthe standard UKF show that the proposed RQAUKF can effectively improve the estimation accuracy and stability,and can assist the controller to obtain better control performance.

Two pHZ1358 Derivative Vectors for Efficient Gene Knockout in Streptomyces

( Yun Long He ),( Zhi Jun Wang ),( Lin Quan Bai ),( Jing Dan Liang ),( Xiu Fen Zhou ),( Zi Xin Deng ) 한국미생물 · 생명공학회 2010 Journal of microbiology and biotechnology Vol.20 No.4

Curcumin Ameliorates Reserpine-Induced Gastrointestinal Mucosal Lesions Through Inhibiting IκB-α/NF-κB Pathway and Regulating Expression of Vasoactive Intestinal Peptide and Gastrin in Rats

Lingli Long,Jingnan Wang,Ningning Chen,Shuhui Zheng,Lanying Shi,Yuxia Xu,Canqiao Luo,Yubin Deng 한국식품영양과학회 2016 Journal of medicinal food Vol.19 No.6

The objective of our study was to investigate whether curcumin protects against reserpine-induced gastrointestinal mucosal lesions (GMLs) in rats and to explore the mechanism of curcumin’s action. Sprague-Dawley rats were randomly divided into four groups: control group, reserpine-treated group, reserpine treatment group with curcumin at high dose (200 mg/kg), and reserpine treatment group with curcumin at low dose (100 mg/kg). Rats in reserpine-treated group were induced by intraperitoneally administered reserpine (0.5 mg/kg) for 28 days. TUNEL staining and hematoxylin and eosin staining were used to evaluate the apoptotic cells and morphologic changes. In addition, to explore the mechanism of curcumin in protecting GMLs, we used serum of experimental rats to assess the level of vasoactive intestinal peptide (VIP), gastrin, interleukin-6, interleukin-10, tumor necrosis factor-α and interferon-γ by ELISA and radioimmunoassay. The protein levels of NF-κB, p-IκB-α, IκB-α, Bcl-2, Bax, and cleaved-caspase-3 were examined by western blot analysis. Data were analyzed with SPSS 19.0 software package. Curcumin treatment prevented tissue damage and cell death in the reserpinetreated rats and effectively decreased inflammatory response and balanced the expression of VIP and gastrin in the reserpinetreated rats. NF-κB, p-IκB-α, Bax, and cleaved-caspase-3 were increased in the reserpine group, but the curcumin high-dose group inhibited them. Curcumin can target the IκB-α/NF-κB pathway to inhibit inflammatory response and regulate the level of VIP and gastrin in reserpine-induced GML rats.

Identification of novel rheumatoid arthritis-associated MiRNA-204-5p from plasma exosomes

Wu Long-Fei,Zhang Qin,Mo Xing-Bo,Lin Jun,Wu Yang-Lin,Lu Xin,He Pei,Wu Jian,Guo Yu-Fan,Wang Ming-Jun,Ren Wen-Yan,Deng Hong-Wen,Lei Shu-Feng,Deng Fei-Yan 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-

Rheumatoid arthritis (RA) is an autoimmune disease characterized by infiltration of immune cells in the synovium. However, the crosstalk of immune cells and synovial fibroblasts is still largely unknown. Here, global miRNA screening in plasma exosomes was carried out with a custom microarray (RA patients vs. healthy controls = 9:9). A total of 14 exosomal miRNAs were abnormally expressed in the RA patients. Then, downregulated expression of exosomal miR-204-5p was confirmed in both the replication (RA patients vs. healthy controls = 30:30) and validation groups (RA patients vs. healthy controls = 56:60). Similar to the findings obtained in humans, a decreased abundance of exosomal miR-204-5p was observed in mice with collagen-induced arthritis (CIA). Furthermore, Spearman correlation analysis indicated that plasma exosomal miR-204-5p expression was inversely correlated with disease parameters of RA patients, such as rheumatoid factor, erythrocyte sedimentation rate, and C-reactive protein. In vitro, our data showed that human T lymphocytes released exosomes containing large amounts of miR-204-5p, which can be transferred into synovial fibroblasts, inhibiting cell proliferation. Overexpression of miR-204-5p in synovial fibroblasts suppressed synovial fibroblast activation by targeting genes related to cell proliferation and invasion. In vivo assays found that administration of lentiviruses expressing miR-204-5p markedly alleviated the disease progression of the mice with CIA. Collectively, this study identified a novel RA-associated plasma exosomal miRNA-204-5p that mediates the communication between immune cells and synovial fibroblasts and can be used as a potential biomarker for RA diagnosis and treatment.

Isolation and Molecular Characterization of a New CRT Binding Factor Gene from Capsella bursa-pastoris

( Xing Long Wang ),( Li Liu ),( Si Xiu Liu ),( Xiao Qing Sun ),( Zhong Xiang Deng ),( Yan Pi ),( Xiao Fen Sun ),( Ke Xuan Tang ) 생화학분자생물학회 2004 BMB Reports Vol.37 No.5

A new CRT binding factor (CBF) gene designated Cbcbf25 was cloned from Capsella bursa pastoris, a wild grass, by the rapid amplification of cDNA ends (RACE). The full-length cDNA of Cbcbf25 was 898 bp with a 669 bp open reading frame (ORF) encoding a putative DRE/CRT (LTRE)-binding protein of 223 amino acids. The predicted CbCBF25 protein contained a potential nuclear localization signal (NLS) in its N-terminal region followed by an AP2 DNA-binding motif and a possible acidic activation domain in the C-terminal region. Bioinformatic analysis revealed that Cbcbf25 has a high level of similarity with other CBF genes like cbfl, cbf2, and cbf3 from Arabidopsis thaliana, and Bncbf5, Bncbf7, Bncbfl6, and Bncbfl7 from Brassica napus. A cold acclimation assay showed that Cbcbf25 was expressed immediately after cold triggering, but this expression was transient, suggesting that it concerns cold acclimation. Our study implies that Cbcbf25 is an analogue of other CBF genes and may participate in cold-response, by for example, controlling the expression of cold-regulated genes or increasing the freezing tolerance of plants.

UKF Based Nonlinear Offset-free Model Predictive Control for Ship Dynamic Positioning under Stochastic Disturbances

Fang Deng,Hua-Lin Yang,Long-Jin Wang,Wei-Min Yang 제어·로봇·시스템학회 2019 International Journal of Control, Automation, and Vol.17 No.12

This paper presents the schemes of nonlinear offset-free model predictive control (MPC) for reference tracking of ship dynamic positioning (DP) systems, in the presence of slow-varying stochastic disturbances and input constraints. Two offset-free MPC strategies for nonlinear DP systems are proposed. The first approach, namely, the target calculation formulation, estimates the disturbance based on the augmented disturbance model, and employs a target calculator to address the MPC optimization problem. The second approach, namely, the delta input formulation, works with the augmented velocity model to lump the effects of disturbances into the input estimates. By successively on-line linearizing the state-space model at the current operating point, the future outputs are explicitly predicted, and then the nonlinear optimization problem becomes an easy quadratic optimization problem. The unscented Kalman filter is adopted for the state estimation. By implementing simulations for two scenarios of disturbances with parametric plant-model mismatch, the effectiveness of the two strategies is demonstrated. Results show that the closed-loop control performance of the delta input formulation method is superior, for its good robustness to the stochastic disturbance.

The Auxiliary Model Based Hierarchical Estimation Algorithms for Bilinear Stochastic Systems with Colored Noises

Chunqiu Guo,Long-Jin Wang,Fang Deng 제어·로봇·시스템학회 2020 International Journal of Control, Automation, and Vol.18 No.3

This paper considers the parameter identification for a class of nonlinear stochastic systems with colored noise. An input-output representation is derived by eliminating the state variables in the bilinear system. Based on the obtained identification model, a recursive generalized extend least squares algorithm is proposed by using the auxiliary model identification idea. Moreover, a two-stage recursive generalized extended least squares algorithm is presented to reduce the computational burden by using the hierarchical identification principle and the auxiliary model identification idea, respectively. A stochastic gradient identification algorithm is proposed for comparison. The simulation results show that the proposed algorithms have a good performance in estimating the parameters of the bilinear systems with colored noises.

Pan-cancer Analysis of Tumor Mutational Burden and Homologous Recombination DNA Damage Repair Using Targeted Next-Generation Sequencing

Hai-Yun Wang,Ling Deng,Ying-Qing Li,Xiao Zhang,Ya-Kang Long,Xu Zhang,Yan-Fen Feng,Yuan He,Tao Tang,Xin-Hua Yang,Fang Wang 대한암학회 2021 Cancer Research and Treatment Vol.53 No.4

Purpose Current variability in methods for tumor mutational burden (TMB) estimation and reporting demonstrates the urgent need for a homogeneous TMB assessment approach. Here, we compared TMB distributions in different cancer types using two customized targeted panels commonly used in clinical practice. Materials and Methods TMB spectra of 295- and 1021-gene panels in multiple cancer types were compared using targeted next-generation sequencing (NGS). The TMB distributions across a diverse cohort of 2,332 cancer cases were then investigated for their associations with clinical features. Treatment response data were collected for 222 patients who received immune-checkpoint inhibitors (ICIs) and their homologous recombination DNA damage repair (HR-DDR) and programmed death-ligand 1 (PD-L1) expression were additionally assessed and compared with the TMB and response rate. Results The median TMB between gene panels was similar despite a wide range in TMB values. The highest TMB was eight and 10 in patients with squamous cell carcinoma and esophageal carcinoma according to the classification of histopathology and cancer types, respectively. Twenty-three out of 103 patients (22.3%) were HR-DDR–positive and could benefit from ICI therapy; out of those 23 patients, seven patients had high TMB (p=0.004). Additionally, PD-L1 expression was not associated with TMB or treatment response among patients receiving ICIs. Conclusion Targeted NGS assays demonstrated the ability to evaluate TMB in pan-cancer samples as a tool to predict response to ICIs. In addition, TMB integrated with HR-DDR–positive status could be a significant biomarker for predicting ICI response in patients.

Preparation and In Vitro Release of Ramose Chitosan-Based-5-Fluorouracil Microspheres

Li, He-Ping,Li, Hui,Wang, Zhou-Dong,Zhang, Juan-Juan,Deng, Man-Feng,Chen, San-Long Korean Chemical Society 2013 대한화학회지 Vol.57 No.1

In order to construct a controlled release system of drugs and to reduce toxic side effects of 5-fluorouracil, the novel ramose chitosan-based-5-fluorouracil microspheres (CS-FU-MS) were prepared. Firstly, using chitosan (CS) as carriers and 5-fluorouracil (5-FU) as a model drug, ramose chitosan-based-5-fluorouracil (CS-FU) was efciently synthesized by chemical crosslinking method through microwave irradiation, drug loading was 10.6%; Secondly, CS-FU-MS were prepared by CS-FU self-assembled under the dialysis conditions and the free 5-FU was encapsulated further at the same time. The size dispersivity of particles is uniform, and the average diameter of the CS-FU-MS was $4{\mu}m$. The drug encapsulation efficiency was 76.1%, and the drug loading was increased to 26.22%. CS-FU-MS maintain the zero-order release time in PBS (pH = 7.4) and HCl/KCl (pH = 1.2) dialysis medium was 40h and 34h respectively, and the cumulative release were 58.89% and 79.33% in 182 h. The results showed that CS-FU-MS have excellent sustained release properties.