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.

Displacement-based design approach for highway bridges with SMA isolators

Jin-long Liu,Songye Zhu,You-lin Xu,Yunfeng Zhang 국제구조공학회 2011 Smart Structures and Systems, An International Jou Vol.8 No.2

As a practical and effective seismic resisting technology, the base isolation system has seen extensive applications in buildings and bridges. However, a few problems associated with conventional leadrubber bearings have been identified after historical strong earthquakes, e.g., excessive permanent deformations of bearings and potential unseating of bridge decks. Recently the applications of shape memory alloys (SMA) have received growing interest in the area of seismic response mitigation. As a result, a variety of SMA-based base isolators have been developed. These novel isolators often lead to minimal permanent deformations due to the self-centering feature of SMA materials. However, a rational design approach is still missing because of the fact that conventional design method cannot be directly applied to these novel devices. In light of this limitation, a displacement-based design approach for highway bridges with SMA isolators is proposed in this paper. Nonlinear response spectra, derived from typical hysteretic models for SMA, are employed in the design procedure. SMA isolators and bridge piers are designed according to the prescribed performance objectives. A prototype reinforced concrete (RC) highway bridge is designed using the proposed design approach. Nonlinear dynamic analyses for different seismic intensity levels are carried out using a computer program called “OpenSees”. The efficacy of the displacement-based design approach is validated by numerical simulations. Results indicate that a properly designed RC highway bridge with novel SMA isolators may achieve minor damage and minimal residual deformations under frequent and rare earthquakes. Nonlinear static analysis is also carried out to investigate the failure mechanism and the self-centering ability of the designed highway bridge.

Displacement-based design approach for highway bridges with SMA isolators

Liu, Jin-Long,Zhu, Songye,Xu, You-Lin,Zhang, Yunfeng Techno-Press 2011 Smart Structures and Systems, An International Jou Vol.8 No.2

As a practical and effective seismic resisting technology, the base isolation system has seen extensive applications in buildings and bridges. However, a few problems associated with conventional lead-rubber bearings have been identified after historical strong earthquakes, e.g., excessive permanent deformations of bearings and potential unseating of bridge decks. Recently the applications of shape memory alloys (SMA) have received growing interest in the area of seismic response mitigation. As a result, a variety of SMA-based base isolators have been developed. These novel isolators often lead to minimal permanent deformations due to the self-centering feature of SMA materials. However, a rational design approach is still missing because of the fact that conventional design method cannot be directly applied to these novel devices. In light of this limitation, a displacement-based design approach for highway bridges with SMA isolators is proposed in this paper. Nonlinear response spectra, derived from typical hysteretic models for SMA, are employed in the design procedure. SMA isolators and bridge piers are designed according to the prescribed performance objectives. A prototype reinforced concrete (RC) highway bridge is designed using the proposed design approach. Nonlinear dynamic analyses for different seismic intensity levels are carried out using a computer program called "OpenSees". The efficacy of the displacement-based design approach is validated by numerical simulations. Results indicate that a properly designed RC highway bridge with novel SMA isolators may achieve minor damage and minimal residual deformations under frequent and rare earthquakes. Nonlinear static analysis is also carried out to investigate the failure mechanism and the self-centering ability of the designed highway bridge.

Treatment of bladder cancer by geoinspired synthetic chrysotile nanocarrier-delivered circPRMT5 siRNA

Chunping Yu,Yi Zhang,Ning Wang,Wensu Wei,Ke Cao,Qun Zhang,Peiying Ma,Dan Xie,Pei Wu,Biao Liu,Jiahao Liu,Wei Xiang,Xing Hu,Xuewen Liu,Jianfei Xie,Jin Tang,Zhi Long,Long Wang,Hongliang Zeng,Jianye Liu 한국생체재료학회 2022 생체재료학회지 Vol.26 No.1

Background: Circular RNAs (circRNAs) have important functions in many fields of cancer biology. In particular, we previously reported that the oncogenic circRNA, circPRMT5, has a major role in bladder cancer progression. Therapy based on circRNAs have good prospects as anticancer strategies. While anti-circRNAs are emerging as therapeutics, the specific in vivo delivery of anti-circRNAs into cancer cells has not been reported and remains challenging. Methods: Synthesized chrysotile nanotubes (SCNTs) with a relatively uniform length (~ 200 nm) have been designed to deliver an siRNA against the oncogenic circPRMT5 (si-circPRMT5) inhibit circPRMT5. In addition, the antitumor effects and safety evaluation of SCNTs/si-circPRMT5 was assessed with a series of in vitro and in vivo assays. Results: The results showed that SCNTs/si-circPRMT5 nanomaterials prolong si-circPRMT5’s half-life in circulation, enhance its specific uptake by tumor cells, and maximize the silencing efficiency of circPRMT5. In vitro, SCNTs encapsulating si-circPRMT5 could inhibit bladder cancer cell growth and progression. In vivo, SCNTs/si-circPRMT5 inhibited growth and metastasis in three bladder tumor models (a subcutaneous model, a tail vein injection lung metastatic model, and an in situ model) without obvious toxicities. Mechanistic study showed that SCNTs/sicircPRMT5 regulated the miR-30c/SNAIL1/E-adherin axis, inhibiting bladder cancer growth and progression. Conclusion: The results highlight the potential therapeutic utility of SCNTs/si-circPRMT5 to deliver si-circPRMT5 to treat bladder cancer.

Bacillus oceani sp. nov., a new slightly halophilic bacterium, isolated from a deep sea sediment environment

Liu, Yu-Juan,Long, Li-Juan,Huang, Xiao-Fang,You, Zhi-Qing,Wang, Fa-Zuo,Li, Jie,Kim, Chang-Jin,Tian, Xin-Peng,Zhang, Si Springer-Verlag 2013 Antonie van Leeuwenhoek Vol.104 No.5

Loss of Heterozygosity at the Calcium Regulation Gene Locus on Chromosome 10q in Human Pancreatic Cancer

Long, Jin,Zhang, Zhong-Bo,Liu, Zhe,Xu, Yuan-Hong,Ge, Chun-Lin Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.6

Background: Loss of heterozygosity (LOH) on chromosomal regions is crucial in tumor progression and this study aimed to identify genome-wide LOH in pancreatic cancer. Materials and Methods: Single-nucleotide polymorphism (SNP) profiling data GSE32682 of human pancreatic samples snap-frozen during surgery were downloaded from Gene Expression Omnibus database. Genotype console software was used to perform data processing. Candidate genes with LOH were screened based on the genotype calls, SNP loci of LOH and dbSNP database. Gene annotation was performed to identify the functions of candidate genes using NCBI (the National Center for Biotechnology Information) database, followed by Gene Ontology, INTERPRO, PFAM and SMART annotation and UCSC Genome Browser track to the unannotated genes using DAVID (the Database for Annotation, Visualization and Integration Discovery). Results: The candidate genes with LOH identified in this study were MCU, MICU1 and OIT3 on chromosome 10. MCU was found to encode a calcium transporter and MICU1 could encode an essential regulator of mitochondrial $Ca^{2+}$ uptake. OIT3 possibly correlated with calcium binding revealed by the annotation analyses and was regulated by a large number of transcription factors including STAT, SOX9, CREB, NF-kB, PPARG and p53. Conclusions: Global genomic analysis of SNPs identified MICU1, MCU and OIT3 with LOH on chromosome 10, implying involvement of these genes in progression of pancreatic cancer.

Preparation of minor ginsenosides C-Mc, C-Y, F2, and C-K from American ginseng PPD-ginsenoside using special ginsenosidase type-I from Aspergillus niger g.848

Liu, Chun-Ying,Zhou, Rui-Xin,Sun, Chang-Kai,Jin, Ying-Hua,Yu, Hong-Shan,Zhang, Tian-Yang,Xu, Long-Quan,Jin, Feng-Xie The Korean Society of Ginseng 2015 Journal of Ginseng Research Vol.39 No.3

Background: Minor ginsenosides, those having low content in ginseng, have higher pharmacological activities. To obtain minor ginsenosides, the biotransformation of American ginseng protopanaxadiol (PPD)-ginsenoside was studied using special ginsenosidase type-I from Aspergillus niger g.848. Methods: DEAE (diethylaminoethyl)-cellulose and polyacrylamide gel electrophoresis were used in enzyme purification, thin-layer chromatography and high performance liquid chromatography (HPLC) were used in enzyme hydrolysis and kinetics; crude enzyme was used in minor ginsenoside preparation from PPD-ginsenoside; the products were separated with silica-gel-column, and recognized by HPLC and NMR (Nuclear Magnetic Resonance). Results: The enzyme molecular weight was 75 kDa; the enzyme firstly hydrolyzed the C-20 position 20-O-${\beta}$-D-Glc of ginsenoside Rb1, then the C-3 position 3-O-${\beta}$-D-Glc with the pathway $Rb1{\rightarrow}Rd{\rightarrow}F2{\rightarrow}C-K$. However, the enzyme firstly hydrolyzed C-3 position 3-O-${\beta}$-D-Glc of ginsenoside Rb2 and Rc, finally hydrolyzed 20-O-L-Ara with the pathway $Rb2{\rightarrow}C-O{\rightarrow}C-Y{\rightarrow}C-K$, and $Rc{\rightarrow}C-Mc1{\rightarrow}C-Mc{\rightarrow}C-K$. According to enzyme kinetics, $K_m$ and $V_{max}$ of Michaelis-Menten equation, the enzyme reaction velocities on ginsenosides were Rb1 > Rb2 > Rc > Rd. However, the pure enzyme yield was only 3.1%, so crude enzyme was used for minor ginsenoside preparation. When the crude enzyme was reacted in 3% American ginseng PPD-ginsenoside (containing Rb1, Rb2, Rc, and Rd) at $45^{\circ}C$ and pH 5.0 for 18 h, the main products were minor ginsenosides C-Mc, C-Y, F2, and C-K; average molar yields were 43.7% for C-Mc from Rc, 42.4% for C-Y from Rb2, and 69.5% for F2 and C-K from Rb1 and Rd. Conclusion: Four monomer minor ginsenosides were successfully produced (at low-cost) from the PPD-ginsenosides using crude enzyme.

The Thioacetate-Functionalized Self-Assembled Monolayers on Au: Toward High-Performance Ion-Selective Electrode for Ag⁺

Jin, Jian,Zhou, Wei-Jie,Chen, Ying,Liu, Yi-Long,Sun, Xiao-Qiang,Xi, Hai-Tao Korean Chemical Society 2014 Bulletin of the Korean Chemical Society Vol.35 No.2

Two classes of morpholino-substitued thioacetate have been successfully synthesized and their electrochemical properties of self-assembled monolayers (SAMs) on Au electrode are measured by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The barrier property of the SAMs-modified surfaces is evaluated by using potassium ferro/ferri cyanide. The results suggest that the arenethioacetate forms higher-quality close-packed blocking monolayers in comparison with alkanethioacetate. Furthermore, it has shown that the barrier properties of these monolayers can be significantly improved by mixed SAMs formation with decanethiol. From our experimental results we find that the electron transfer reaction of $[Fe(CN)_6]^{3/4-}$ redox couple occurs predominantly through the pinholes and defects present in the SAM and both SAMs show a good and fast capacity in recognition for $Ag^+$. The morphological and elementary composition have also been examined by scanning electron microscope (SEM) and energy dispersive spectrometer (EDS).

<i>Chd7</i> Is Critical for Early T-Cell Development and Thymus Organogenesis in Zebrafish

Liu, Zhi-Zhi,Wang, Zi-Long,Choi, Tae-Ik,Huang, Wen-Ting,Wang, Han-Tsing,Han, Ying-Ying,Zhu, Lou-Yin,Kim, Hyun-Taek,Choi, Jung-Hwa,Lee, Jin-Soo,Kim, Hyung-Goo,Zhao, Jian,Chen, Yue,Lu, Zhuo,Tian, Xiao-L Elsevier 2018 The American journal of pathology Vol.188 No.4

<P>Coloboma, heart defect, atresia choanae, retarded growth and development, genital hypoplasia, ear anomalies/deafness (CHARGE) syndrome is a congenital disorder affecting multiple organs and mainly caused by mutations in CHD7, a gene encoding a chromatin-remodeling protein. Immunodeficiency and reduced T cells have been noted in CHARGE syndrome. However, the mechanisms underlying T lymphopenia are largely unexplored. Herein, we observed dramatic decrease of T cells in both chd7knockdown and knockout zebrafish embryos. Unexpectedly, hematopoietic stem and progenitor cells and, particularly, lymphoid progenitor cells were increased peripherally in nonthymic areas in chd7-deficient embryos, unlikely to contribute to the T-cell decrease. Further analysis demonstrated that both the organogenesis and homing function of the thymus were seriously impaired. Chd7 might regulate thymus organogenesis through modulating the development of both neural crest cell-derived mesenchyme and pharyngeal endoderm-derived thymic epithelial cells. The expression of faxn1, a central regulator of thymic epithelium, was remarkably down-regulated in the pharyngeal region in chd7-deficient embryos. Moreover, the T-cell reduction in chd7-deficient embryos was partially rescued by overexpressingfoxnl, suggesting that restoring thymic epithelium may be a potential therapeutic strategy for treating immunodeficiency in CHARGE syndrome. Collectively, the results indicated that chd7 was critical for thymic development and T-lymphopenia in CHARGE syndrome may be mainly attributed to the defects of thymic organogenesis. The current finding may benefit the diagnosis and therapy of T lymphopenia and immunodeficiency in CHARGE syndrome.</P>

Micro Galvanic Cell To Generate PtO and Extend the Triple-Phase Boundary during Self-Assembly of Pt/C and Nafion for Catalyst Layers of PEMFC

Long, Zhi,Gao, Liqin,Li, Yankai,Kang, Baotao,Lee, Jin Yong,Ge, Junjie,Liu, Changpeng,Ma, Shuhua,Jin, Zhao,Ai, Hongqi American Chemical Society 2017 ACS APPLIED MATERIALS & INTERFACES Vol.9 No.44

<P>The self-assembly powder (SAP) with varying Nafion content was synthesized and characterized by XRD, XPS, HRTEM, and mapping. It is observed that the oxygen from oxygen functional groups transfers to the surface of Pt and generate PtO during the process of self-assembly with the mechanism of micro galvanic cell, where Pt, carbon black, and Nafion act as the anode, cathode and electrolyte, respectively. The appearance of PtO on the surface of Pt leads to a turnover of Nafion structure, and therefore more hydrophilic sulfonic groups directly contact with Pt, and thus the triple-phase boundary (TPB) has been expanded.</P>