CDH17 nanobodies facilitate rapid imaging of gastric cancer and efficient delivery of immunotoxin

Jingbo Ma,Xiaolong Xu,Chunjin Fu,Peng Xia,Ming Tian,Liuhai Zheng,Kun Chen,Xiaolian Liu,Yilei Li,Le Yu,Qinchang Zhu,Yangyang Yu,Rongrong Fan,Haibo Jiang,Zhifen Li,Chuanbin Yang,Chengchao Xu,Ying Long,J 한국생체재료학회 2022 생체재료학회지 Vol.26 No.4

Background: It is highly desirable to develop new therapeutic strategies for gastric cancer given the low survival rate despite improvement in the past decades. Cadherin 17 (CDH17) is a membrane protein highly expressed in cancers of digestive system. Nanobody represents a novel antibody format for cancer targeted imaging and drug delivery. Nanobody targeting CHD17 as an imaging probe and a delivery vehicle of toxin remains to be explored for its theragnostic potential in gastric cancer. Methods: Naïve nanobody phage library was screened against CDH17 Domain 1-3 and identified nanobodies were extensively characterized with various assays. Nanobodies labeled with imaging probe were tested in vitro and in vivo for gastric cancer detection. A CDH17 Nanobody fused with toxin PE38 was evaluated for gastric cancer inhibition in vitro and in vivo. Results: Two nanobodies (A1 and E8) against human CDH17 with high affinity and high specificity were successfully obtained. These nanobodies could specifically bind to CDH17 protein and CDH17-positive gastric cancer cells. E8 nanobody as a lead was extensively determined for tumor imaging and drug delivery. It could efficiently co-localize with CDH17-positive gastric cancer cells in zebrafish embryos and rapidly visualize the tumor mass in mice within 3 h when conjugated with imaging dyes. E8 nanobody fused with toxin PE38 showed excellent anti-tumor effect and remarkably improved the mice survival in cell-derived (CDX) and patient-derived xenograft (PDX) models. The immunotoxin also enhanced the anti-tumor effect of clinical drug 5-Fluorouracil. Conclusions: The study presents a novel imaging and drug delivery strategy by targeting CDH17. CDH17 nanobodybased immunotoxin is potentially a promising therapeutic modality for clinical translation against gastric cancer.

Soil characteristics and new formation model of loess on the Chinese Loess Plateau

Jingbo Zhao,Xiaoqing Luo,Yandong Ma,Tianjie Shao,Yingli Yue 한국지질과학협의회 2017 Geosciences Journal Vol.21 No.4

In this paper characteristics of loess are discussed from a pedological perspective. A new model of loess formation is presented, developed in different soil formation processes according to its pedogenic characteristics, including soil structure, organic matter content and CaCO3 content. Loess has all the characteristics of typical soils and all five soil-forming factors have important roles in loess formation. In this regard, loess is a type soil and the previous concept of loess actually comprises various kinds of palaeosols developed in cold and arid climatic conditions. The loess-forming process is, in fact, equivalent to a pedogenic process and loess layers with different characteristics represent different pedogenic processes indicative of different environments, such as desert-steppe, steppe or forest-steppe climatic conditions. In contrast to red-brown palaeosol layers, which develop in warm and wet climates, loesses – more accurately called ‘loessial palaeosols’ – are grey-yellow palaeosols and can be regarded as a reliable indicator of cold and arid climate. The model of loess formation suggests that aeolian dust transfers to grey-yellow palaeosols via pedogenesis and the characteristics of loess are mainly a result of climatic conditions and diagenesis processes after its sedimentation. This new model of loess formation also suggests that traditional pedological theory has its limitations when explaining soil formation processes.

Occlusal deviations in adolescents with idiopathic and congenital scoliosis

Zhang Hao,Ma Jingbo,Zhang Zhicheng,Feng Yafei,Cai Chuan,Wang Chao 대한치과교정학회 2022 대한치과교정학회지 Vol.52 No.3

Objective: This cross-sectional study aimed to investigate the characteristics of malocclusions in scoliotic patients through clinical examinations. Methods: Fifty-eight patients with idiopathic scoliosis (IS) and 48 patients with congenital scoliosis (CS) participated in the study. A randomly selected group of 152 orthopedically healthy children served as the control group. Standardized orthodontic and orthopedic examination protocols were used to record the occlusal patterns and type of scoliosis. Assessments were made by three experienced orthodontists and a spinal surgery team. The differences in the frequency distribution of occlusal patterns were evaluated by the chi-squared test. Results: In comparison with patients showing IS, patients with CS showed a higher incidence of Cobb angle ≥ 45° (p = 0.020) and included a higher proportion of patients receiving surgical treatments (p < 0.001). The distribution of the Angle Class II subgroup was significantly higher in the IS (p < 0.001) and CS (p = 0.031) groups than in the control group. In comparison with the healthy controls, the CS and IS groups showed significantly higher (p < 0.05) frequencies of asymmetric molar and asymmetric canine relationships, upper and lower middle line deviations, anterior deep overbite, unilateral posterior crossbite, and canted occlusal plane, with the frequencies being especially higher in CS patients and to a lesser extent in IS patients. Conclusions: Patients with scoliosis showed a high frequency of malocclusions, which were most obvious in patients with CS.

Hypolipidemic Effects of Hickory Nut Oil using Cold Pressure Extraction

Yan Zhang,Liying Wu,Zhixin Yao,Zhongsu Ma,Jingbo Liu 한국식품과학회 2016 Food Science and Biotechnology Vol.25 No.suppl1

Optimal conditions of hickory nut oil cold press technology were studied. L9(34) orthogonal experiment results showed that optimal conditions were a pressing pressure of 15 MPa, pressing temperature of 50oC, pressing cycle of 4 s, and stop cycle of 9 s. Fatty acid compositions were determined using GC-MS and hypolipidemic effects in mice were investigated. Compared to a high fat diet group, hickory nut oil administration decreased serum and visceral total cholesterol, triacylglycerol, and serum low density lipoprotein cholesterol levels. Serum high density lipoprotein cholesterol values were increased. Hickory nut oil can be used as a valuable bioactive source of natural hypolipidemic compounds.

The beneficial effect of ginsenosides extracted by pulsed electric field against hydrogen peroxide-induced oxidative stress in HEK-293 cells

Di Liu,Ting Zhang,Zhifei Chen,Ying Wang,Shuang Ma,Jiyun Liu,Jingbo Liu 고려인삼학회 2017 Journal of Ginseng Research Vol.41 No.2

Background: Ginsenosides are the main pharmacological components of Panax ginseng root, which are thought to be primarily responsible for the suppressing effect on oxidative stress. Methods: 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity and oxygen radical absorption capacity were applied to evaluate the antioxidant activities of the ginsenosides. Human embryonic kidney 293 (HEK-293) cells were incubated with ginsenosides extracted by pulsed electric field (PEF) and solvent cold soak extraction (SCSE) for 24 h and then the injury was induced by 40mM H2O2. The cell viability and surface morphology of HEK-293 cells were studied using MTS assay and scanning electron microscopy, respectively. Dichloro-dihydro-fluorescein diacetate fluorescent probe assay was used to measure the level of intracellular reactive oxygen species. The intracellular antioxidant activities of ginsenosides were evaluated by cellular antioxidant activity assay in HepG2 cells. Results: The PEF extracts displayed the higher 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity and stronger oxygen radical absorption capacity (with an oxygen radical absorption capacity value of 14.48 4.04mM TE per mg/mL). The HEK-293 cell model also suggested that the protective effect of PEF extracts was dose-dependently greater than SCSE extracts. Dichloro-dihydro-fluorescein diacetate assay further proved that PEF extracts are more active (8% higher than SCSE extracts) in reducing intracellular reactive oxygen species accumulation. In addition, scanning electron microscopy images showed that the HEK-293 cells, which were treated with PEF extracts, maintained more intact surface morphology. Cellular antioxidant activity values indicated that ginsenosides extracted by PEF had stronger cellular antioxidant activity than SCSE ginsenosides extracts. Conclusion: The present study demonstrated the antioxidative effect of ginsenosides extracted by PEF in vitro. Furthermore, rather than SCSE, PEF may be more useful as an alternative extraction technique for the extraction of ginsenosides with enhanced antioxidant activity.

The beneficial effect of ginsenosides extracted by pulsed electric field against hydrogen peroxide-induced oxidative stress in HEK-293 cells

Liu, Di,Zhang, Ting,Chen, Zhifei,Wang, Ying,Ma, Shuang,Liu, Jiyun,Liu, Jingbo The Korean Society of Ginseng 2017 Journal of Ginseng Research Vol.41 No.2

Background: Ginsenosides are the main pharmacological components of Panax ginseng root, which are thought to be primarily responsible for the suppressing effect on oxidative stress. Methods: 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity and oxygen radical absorption capacity were applied to evaluate the antioxidant activities of the ginsenosides. Human embryonic kidney 293 (HEK-293) cells were incubated with ginsenosides extracted by pulsed electric field (PEF) and solvent cold soak extraction (SCSE) for 24 h and then the injury was induced by $40{\mu}M$ $H_2O_2$. The cell viability and surface morphology of HEK-293 cells were studied using MTS assay and scanning electron microscopy, respectively. Dichloro-dihydro-fluorescein diacetate fluorescent probe assay was used to measure the level of intracellular reactive oxygen species. The intracellular antioxidant activities of ginsenosides were evaluated by cellular antioxidant activity assay in HepG2 cells. Results: The PEF extracts displayed the higher 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity and stronger oxygen radical absorption capacity (with an oxygen radical absorption capacity value of $14.48{\pm}4.04{\mu}M\;TE\;per\;{\mu}g/mL$). The HEK-293 cell model also suggested that the protective effect of PEF extracts was dose-dependently greater than SCSE extracts. Dichloro-dihydro-fluorescein diacetate assay further proved that PEF extracts are more active (8% higher than SCSE extracts) in reducing intracellular reactive oxygen species accumulation. In addition, scanning electron microscopy images showed that the HEK-293 cells, which were treated with PEF extracts, maintained more intact surface morphology. Cellular antioxidant activity values indicated that ginsenosides extracted by PEF had stronger cellular antioxidant activity than SCSE ginsenosides extracts. Conclusion: The present study demonstrated the antioxidative effect of ginsenosides extracted by PEF in vitro. Furthermore, rather than SCSE, PEF may be more useful as an alternative extraction technique for the extraction of ginsenosides with enhanced antioxidant activity.

Cadherin 17 Nanobody-Mediated Near-Infrared-II Fluorescence Imaging-Guided Surgery and Immunotoxin Delivery for Colorectal Cancer

Youbin Ding,Runhua Zhou,Guangwei Shi,Yuke Jiang,Zhifen Li,Xiaolong Xu,Jingbo Ma,Jingnan Huang,Chunjin Fu,Hongchao Zhou,Huifang Wang,Jiexuan Li,Zhiyu Dong,Qingling Yu,Kexin Jiang,Yehai An,Yawei Liu,Yil 한국생체재료학회 2024 생체재료학회지 Vol.28 No.00

Surgery and targeted therapy are of equal importance for colorectal cancer (CRC) treatment. However, complete CRC tumor resection remains challenging, and new targeted agents are also needed for efficient CRC treatment. Cadherin 17 (CDH17) is a membrane protein that is highly expressed in CRC and, therefore, is an ideal target for imaging-guided surgery and therapeutics. This study utilizes CDH17 nanobody (E8-Nb) with the near-infrared (NIR) fluorescent dye IRDye800CW to construct a NIR-II fluorescent probe, E8-Nb-IR800CW, and a Pseudomonas exotoxin (PE)-based immunotoxin, E8-Nb-PE38, to evaluate their performance for CRC imaging, imaging-guided precise tumor excision, and antitumor effects. Our results show that E8-Nb-IR800CW efficiently recognizes CDH17 in CRC cells and tumor tissues, produces high-quality NIR-II images for CRC tumors, and enables precise tumor removal guided by NIR-II imaging. Additionally, fluorescent imaging confirms the targeting ability and specificity of the immunotoxin toward CDH17-positive tumors, providing the direct visible evidence for immunotoxin therapy. E8-Nb-PE38 immunotoxin markedly delays the growth of CRC through the induction of apoptosis and immunogenic cell death (ICD) in multiple CRC tumor models. Furthermore, E8-Nb-PE38 combined with 5-FU exerts synergistically antitumor effects and extends survival. This study highlights CDH17 as a promising target for CRC imaging, imaging-guided surgery, and drug delivery. Nanobodies targeting CDH17 hold great potential to construct NIR-II fluorescent probes for surgery navigation, and PE-based toxins fused with CDH17 nanobodies represent a novel therapeutic strategy for CRC treatment. Further investigation is warranted to validate these findings for potential clinical translation.