1.Fibroblast activation protein targeting radiopharmaceuticals: From drug design to clinical translation.
Yuxuan WU ; Xingkai WANG ; Xiaona SUN ; Xin GAO ; Siqi ZHANG ; Jieting SHEN ; Hao TIAN ; Xueyao CHEN ; Hongyi HUANG ; Shuo JIANG ; Boyang ZHANG ; Yingzi ZHANG ; Minzi LU ; Hailong ZHANG ; Zhicheng SUN ; Ruping LIU ; Hong ZHANG ; Ming-Rong ZHANG ; Kuan HU ; Rui WANG
Acta Pharmaceutica Sinica B 2025;15(9):4511-4542
The activation proteins released by fibroblasts in the tumor microenvironment regulate tumor growth, migration, and treatment response, thereby influencing tumor progression and therapeutic outcomes. Owing to the proliferation and metastasis of tumors, fibroblast activation protein (FAP) is typically highly expressed in the tumor stroma, whereas it is nearly absent in adult normal tissues and benign lesions, making it an attractive target for precision medicine. Radiolabeled agents targeting FAP have the potential for targeted cancer diagnosis and therapy. This comprehensive review aims to describe the evolution of FAPI-based radiopharmaceuticals and their structural optimization. Within its scope, this review summarizes the advances in the use of radiolabeled small molecule inhibitors for tumor imaging and therapy as well as the modification strategies for FAPIs, combined with insights from structure-activity relationships and clinical studies, providing a valuable perspective for radiopharmaceutical clinical development and application.
2.Effect of Fushengong Prescreption on Regulation-antagonism Effect of ACE-AngⅡ-AT1R Axis and ACE2-Ang(1-7)-MASR Axis of Rats with Chronic Renal Failure
Ke XU ; Xue-kuan HUANG ; Qing SHEN ; Yang ZHANG ; Hong-yu LUO ; Jia-yu TIAN ; Bo ZOU ; Qin YANG ; Ke-ming HOU
Chinese Journal of Experimental Traditional Medical Formulae 2021;27(5):62-69
Objective:To study the effect of Fushengong prescreption on the regulation-antagonism effect of angiotensin converting enzyme-angiotensin Ⅱ-angiotensin Ⅱ 1 receptor (ACE-AngⅡ-AT1R) axis and angiotensin converting enzyme 2-angiotensin (1-7)-Mas receptor[ACE2-Ang(1-7)-MASR] axis of rats with chronic renal failure(CRF), and to explore its mechanism of delaying the development of CRF. Method:The 65 male SD rats were randomly divided into normal group (
3.Effect of Fushengong Prescription on Wnt/β-catenin Signaling Pathway in Kidney of Rats with Chronic Renal Failure
Yang ZHANG ; Xue-kuan HUANG ; Qing SHEN ; Pan TONG ; Ke XU ; Hong-yu LUO ; Jia-yu TIAN ; Bo ZOU ; Shi YIN
Chinese Journal of Experimental Traditional Medical Formulae 2020;26(24):89-95
Objective:To observe the effects of Fushengong prescription on secretory glycoprotein (Wnt)/
4.Effect of Fushengong Prescription on p38 MAPK Signal Pathway of Rats with Chronic Renal Failure
Pan TONG ; Xue-kuan HUANG ; Qing SHEN ; Yang ZHANG ; Ke XU ; Hong-yu LUO
Chinese Journal of Experimental Traditional Medical Formulae 2020;26(14):105-110
Objective:To observe the effects of Fushengong prescription on p38 mitogen-activated protein kinase(p38 MAPK) signal pathway of rats with chronic renal failure(CRF),and to explore its mechanism of reducing inflammatory reaction of renal tissues and delaying the progress of renal interstitial fibrosis. Method:The 55 male Sprague-Dawley rats were randomly divided into normal group,model group, and low,medium and high dose groups of Fushengong prescription,with 11 rats in each group.The normal group was routinely reared, and the other four groups of rats were fed a diet containing 0.5% adenine to produce a model of CRF, which was continuously molded for 21 days.After successful modeling,all rats switched to conventional feed.Normal group and model group were given normal saline 20 mL·kg-1,and each group of Fushengong prescription was given 4,8,16 g·kg-1 of water prescription once a day for 30 days.After the experiment,Masson staining was used to observe the degree of renal interstitial fibrosis.The expression of monocyte chemotactic protein-1(MCP-1) in renal tissues was detected by immunohistochemistry. The expression of phosphorylated p38 mitogen-activated protein kinase(p-p38 MAPK) and transformed growth factor-
5.Investigation on the internalization pathway of microparticles into human umbilical cord endothelial cells.
Xiao-Juan WEI ; Hong-Chao ZHANG ; Zheng-Zheng SHEN ; Fang WANG ; Yan WANG ; Zi-Kuan GUO ; Chao-Zhong LIU
Journal of Experimental Hematology 2015;23(2):495-499
OBJECTIVETo investigate the mechanisms underlying the incorporation of microparticles(MP) derived from human bone marrow mesenchymal stem cells (MSCs) into human umbilical cord endothelial cells (HUVECs).
METHODSMPs were isolated from the supernatants of MSCs which had exposed to a hypoxia/serum-deprivation condition. Electron microscope was used to identify the MPs. The surface molecule profile was evaluated with the bead-based flow cytometry technique. The expression level of the phosphatidylserine receptor (PSR) was detected by immunofluorescence cytochemistry. MPs were co-cultured with HUVECs in the presence or absence PSR-antibody, and the internalization of MPs was observed with laser scanning microscopy.
RESULTSThe MPs derived from MSCs expressed highly PS, while PSR expressed on the surface of HUVECs. The confocal result revealed that MPs could quickly be uptaken by the endothelial cells, and mainly distributed in the cytoplasm surrounding of the nuclei. The internalization of MPs reduced significantly after PSR specific blockage.
CONCLUSIONThe reaction between PS on the MP and the PSR of HUVECs plays an important role in the internalization of MSC-MPs.
Cells, Cultured ; Coculture Techniques ; Endothelial Cells ; Flow Cytometry ; Humans ; Mesenchymal Stromal Cells ; Umbilical Cord
6.Construction of a human cervical spine with bilateral vertebral artery fluid-solid coupling model.
Hui-hao WANG ; Zhi-bi SHEN ; Zhen DENG ; Kuan WANG ; Hong-sheng ZHAN ;
Journal of Zhejiang University. Medical sciences 2015;44(2):131-137
OBJECTIVETo construct a human cervical spine with bilateral vertebral artery fluid-solid coupling model.
METHODSHelical CT images under the principle of reverse engineering and meshed in finite element model(FEM) related software were used to establish a human cervical spine with bilateral vertebral artery fluid-solid coupling model. In the process of modeling of vertebral body, vertebral artery, ligament, intervertebral disc, cartilage and endplate large anatomic data and cadaver experiments results were referenced. From the morphology and function the simulation of model with real physiological status was tested.
RESULTSThe study showed that the stress concentration on the surface of vertebral body and the blood wall of the bilateral vertebral artery, and the result of the volume flow rate-time curve of bilateral vertebral artery of the model were consistent with the published literatures. This model was well consistent with the clinical phenomenon.
CONCLUSIONThe three-dimensional FEM of the human cervical spine established by the introduced method has been effectively verified. The modeling method would provide a new tool for research on the cervical spine biomechanics.
Biomechanical Phenomena ; Cadaver ; Cervical Vertebrae ; anatomy & histology ; Finite Element Analysis ; Humans ; Intervertebral Disc ; Models, Anatomic ; Tomography, Spiral Computed ; Vertebral Artery ; anatomy & histology
7.Construction of a human cervical spine with bilateral vertebral artery fluid-solid coupling model
Hui-Hao WANG ; Zhi-Bi SHEN ; Zhen DENG ; Kuan WANG ; Hong-Sheng ZHAN
Journal of Zhejiang University. Medical sciences 2015;(2):131-137
Objective: To construct a human cervical spine with bilateral vertebral artery fluid-solid coupling model .Methods: Helical CT images under the principle of reverse engineering and meshed in finite element model ( FEM ) related software were used to establish a human cervical spine with bilateral vertebral artery fluid-solid coupling model . In the process of modeling of vertebral body , vertebral artery , ligament , intervertebral disc , cartilage and endplate large anatomic data and cadaver experiments results were referenced .From the morphology and function the simulation of model with real physiological status was tested .Results: The study showed that the stress concentration on the surface of vertebral body and the blood wall of the bilateral vertebral artery , and the result of the volume flow rate-time curve of bilateral vertebral artery of the model were consistent with the published literatures .This model was well consistent with the clinical phenomenon .Conclusion: The three-dimensional FEM of the human cervical spine established by the introduced method has been effectively verified.The modeling method would provide a new tool for research on the cervical spine biomechanics .
8.Pressure therapy upregulates matrix metalloproteinase expression and downregulates collagen expression in hypertrophic scar tissue.
Dong HUANG ; Kuan-Hong SHEN ; Hong-Gang WANG
Chinese Medical Journal 2013;126(17):3321-3324
BACKGROUNDPressure therapy improves hypertrophic scar healing, but the mechanisms for this process are not well understood. We sought to investigate the differential expression of matrix metalloproteinases (Mmps) and collagen in posttraumatic hypertrophic scar tissue with mechanical pressure and delineate the molecular mechanisms of pressure therapy for hypertrophic scars.
METHODSFibroblast lines of normal skin and scar tissue were established and a mechanical pressure system was devised to simulate pressure therapy. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting assays were used to compare differences in the mRNA and protein expression of Mmps and collagen in scar fibroblasts before and after pressure therapy.
RESULTSThe expression differed between the hypertrophic scar cell line and the normal cell line. RT-PCR assays showed that Collagen I, highly expressed in the hypertrophic scar cell line, decreased significantly after pressure therapy. Mmp2, Mmp9, and Mmp12 expression in the hypertrophic scar tissue increased significantly after pressure therapy (P < 0.05). Western blotting assays further revealed that Mmp9 and Mmp12 expression increased significantly in the hypertrophic scar tissue after pressure therapy (P < 0.05) but not Mmp2 expression (P > 0.05).
CONCLUSIONMechanical pressure induces degradation of Collagen I in hypertrophic scar tissue by affecting the expression of Mmp9 and Mmp12.
Cell Line ; Cicatrix, Hypertrophic ; enzymology ; metabolism ; Collagen Type I ; genetics ; metabolism ; Humans ; Matrix Metalloproteinase 12 ; genetics ; metabolism ; Matrix Metalloproteinase 2 ; genetics ; metabolism ; Matrix Metalloproteinase 9 ; genetics ; metabolism
9.Research on genotyping of methicillin-resistant Staphylococcus aureus in China
En-Hua SHEN ; Li-Hong WANG ; Hui WANG ; Hong-Li SUN ; Min-Jun CHEN ; Jing YUAN ; Yan-Kuan WANG
Chinese Journal of Epidemiology 2010;31(3):308-311
Objective To investigate the source and genetic background of methicillin-resistant Staphylococcus aureus in the year of 2006,in China. Methods From January to December 2006,a total number of 302 consecutive and non-repetitive methicillin-resistant Staphylococcus aureus were collected from 17 Teaching hospitals in 15 areas. Genotypes of SCCmec were determined by multiplex PCR and multilocus sequence typing (MLST) was used to type the house-keeping genes. The implementation of the spa typing method was straightforward,and the results obtained were reproducible,unambiguous,and easily interpreted. Results All areas but Dalian harbored SCCmec Ⅲ while Dalian harbored SCCmec Ⅱ most. There were two strains in Guangzhou,harboring SCCmec Ⅳ. There were four strains of sequence type(ST),with ST239 accounted for 46.7% and ST5 accounted for 44.4%. ST59 accounted for 6.7% and ST88 accounted for 2.2%. There were fourteen strains of Spa typing,with t30 accounted for 52.6% ; t37 accounted for 27.2% ; t2 accounted for 12.9% ; t632 accounted for 2.3% ; t437 accounted for 1.3% ; t570,t601 accounted for 0.7% ; t377,t459,t796,t899,t1152,t2649 accounted for 0.3% ; no-typing accounted for 0.3%,respectively,pvl gene was not detected. Conclusion The main clone strains were ST239-MRSA-SCCmec Ⅲ-t30,ST5-MRSA-SCCmec Ⅱ-t2,with unique geographic distributions across the whole nation.
10.Molecular characterization of embB306 gene in Mycobacterium tuberculosis isolates from tuberculosis patients in Chongqing municipality.
Hui LIN ; Jie LIU ; Lin CHEN ; Kuan-he JING ; Jing SHEN ; Jian ZHAN ; Ya-fei LI ; Ru-fu XU ; Hong-yan XIONG ; Jia CAO
Chinese Journal of Preventive Medicine 2009;43(3):223-226
OBJECTIVETo understand the characteristics of embB gene mutation of Mycobacterium tuberculosis (MTB) isolates from tuberculosis patients in Chongqing, and the value of embB306 as a molecular marker used to diagnose ethambutol (EMB)-resistant MTB strains.
METHODSDirect sequencing was used to analyze the polymorphism of embB mutation in 51 EMB-resistant MTB strains and 50 EMB-sensitive MTB strains. And diagnostic testing was used to evaluate the value of embB306 as a molecular marker of EMB -resistant MTB strains as compared with the traditional sensitivity test.
RESULTSAll 34 of 51 EMB-resistant strains (66.7%) and 3 of 51 EMB-sensitive strains (6%) had had embB306 mutation. The embB306 mutation rate in EMB-resistant strains coming from previously treated case was 87.5%, showing significantly higher than that from new cases (48.1%, P < 0.01); embB306 mutation rate was increased with the number of the resistant drugs; embB306 mutation serving as a marker to diagnose EMB-resistant MTB strains comparing with the traditional sensitivity test, had the rate of sensitivity = 66.7%, specificity = 94.0%, accuracy = 80.2% and Youden index = 60.7%.
CONCLUSIONembB306 mutation should be the main mechanism of MTB resistance to EMB in Chongqing, showing an association with the history of the treated and numbers of the resistant drugs. embB306 mutation should be a good marker to diagnose EMB-resistant MTB strains.
China ; DNA Mutational Analysis ; DNA, Bacterial ; genetics ; Genes, Bacterial ; Humans ; Mutation ; Mycobacterium tuberculosis ; drug effects ; genetics ; isolation & purification ; Pentosyltransferases ; genetics ; Tuberculosis, Multidrug-Resistant ; microbiology

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