1.Chinese agarwood petroleum ether extract suppressed gastric cancer progression via up-regulation of DNA damage-induced G0/G1 phase arrest and HO-1-mediated ferroptosis.
Lishan OUYANG ; Xuejiao WEI ; Fei WANG ; Huiming HUANG ; Xinyu QIU ; Zhuguo WANG ; Peng TAN ; Yufeng GAO ; Ruoxin ZHANG ; Jun LI ; Zhongdong HU
Chinese Journal of Natural Medicines (English Ed.) 2025;23(10):1210-1220
Gastric cancer (GC) is characterized by high morbidity and mortality rates. Chinese agarwood comprises the resin-containing wood of Aquilaria sinensis (Lour.) Gilg., traditionally utilized for treating asthma, cardiac ischemia, and tumors. However, comprehensive research regarding its anti-GC effects and underlying mechanisms remains limited. In this study, Chinese agarwood petroleum ether extract (CAPEE) demonstrated potent cytotoxicity against human GC cells, with half maximal inhibitory concentration (IC50) values for AGS, HGC27, and MGC803 cells of 2.89, 2.46, and 2.37 μg·mL-1, respectively, at 48 h. CAPEE significantly induced apoptosis in these GC cells, with B-cell lymphoma-2 (BCL-2) associated X protein (BAX)/BCL-2 antagonist killer 1 (BAK) likely mediating CAPEE-induced apoptosis. Furthermore, CAPEE induced G0/G1 phase cell cycle arrest in human GC cells via activation of the deoxyribonucleic acid (DNA) damage-p21-cyclin D1/cyclin-dependent kinase 4 (CDK4) signaling axis, and increased Fe2+, lipid peroxides and reactive oxygen species (ROS) levels, thereby inducing ferroptosis. Ribonucleic acid (RNA) sequencing, real-time quantitative polymerase chain reaction (RT-qPCR), and Western blotting analyses revealed CAPEE-mediated upregulation of heme oxygenase-1 (HO-1) in human GC cells. RNA interference studies demonstrated that HO-1 knockdown reduced CAPEE sensitivity and inhibited CAPEE-induced ferroptosis in human GC cells. Additionally, CAPEE administration exhibited robust in vivo anti-GC activity without significant toxicity in nude mice while inhibiting tumor cell growth and promoting apoptosis in tumor tissues. These findings indicate that CAPEE suppresses human GC cell growth through upregulation of the DNA damage-p21-cyclin D1/CDK4 signaling axis and HO-1-mediated ferroptosis, suggesting its potential as a candidate drug for GC treatment.
Animals
;
Humans
;
Mice
;
Antineoplastic Agents, Phytogenic
;
Apoptosis/drug effects*
;
Cell Line, Tumor
;
Cyclin D1/genetics*
;
Cyclin-Dependent Kinase 4/genetics*
;
DNA Damage/drug effects*
;
Drugs, Chinese Herbal/pharmacology*
;
Ferroptosis/drug effects*
;
G1 Phase Cell Cycle Checkpoints/drug effects*
;
Heme Oxygenase-1/genetics*
;
Mice, Inbred BALB C
;
Mice, Nude
;
Plant Extracts/pharmacology*
;
Stomach Neoplasms/physiopathology*
;
Thymelaeaceae/chemistry*
;
Up-Regulation/drug effects*
2.An experimental study on TRIM21 promoting M1 polarization of macrophages to aggravate chronic apical periodontitis
Jingying ZHANG ; Xiaochuan LIU ; Xiaoqin XU ; Peiqi LIANG ; Jinsi WANG ; Hong ZHU ; Yueying WANG ; Zhuguo WU
Journal of Practical Stomatology 2024;40(5):652-660
Objective:To explore the role of tripartite motif-containing protein 21(TRIM21)in chronic apical periodontitis(CAP)and its potential mechanism.Methods:Human CAP tissue and normal periodontal tissue were collected.The expression of inflamma-tory factors(IL-1 β,IL-6,TNF-a,TGF-β1),osteoclast related genes(TRAP,RANKL,CTSK),macrophage polarization related genes(CD86,iNOS,CD206,Arg1)and TRIM21 were detected by RT-qPCR.TRIM21 protein was detected by immunohistochemical staining,and the osteoclasts was detected by tartrate resistant acid phosphatase(TRAP)staining.The inflammation cell model was es-tablished by stimulating Raw264.7 cells with lipoteichoic acid(LTA)or lipopolysaccharide(LPS),and the expression of the above factors was detected.The bone marrow-derived macrophages(BMDMs)extracted from wild-type and TRIM21-/-mice stimulated by LPS were used to verify the expression of the above factors by RT-qPCR,the osteoclasts were detected by TRAP staining,and the po-larization of macrophages was detected by immunofluorescence staining.Results:In CAP tissue the expression of inflammatory factors,osteoclast related genes,CD86,iNOS and TRIM21 increased,while CD206 and Arg1 decreased,and osteoclasts were more than that in normal tissue.The stimulation of LTA/LPS promoted the proliferation of Raw264.7 cells,and the expression of these factors in cells was consistent with that in tissues.After LPS stimulation,BMDMs of TRIM21-/-mice had lighter inflammation,lower expression of os-teoclast specific genes,fewer osteoclasts and lower M1 polarization than those of wild type mice.Conclusion:TRIM21 might promote the progress of CAP by promoting M1 polarization of macrophages.
3.Cloning and synthesis of a new A-superfamily conotoxin Bt14.10
Fei WANG ; Longxiao ZHANG ; Liang LI ; Zhuguo LIU ; Qiuyun DAI
Military Medical Sciences 2014;(8):598-601
Objective To clone a new conotoxin Bt14.10 from Conus betulinus derived from the South China Sea, synthesize the peptide , and to determine linkage of its disulfide bridges .Methods The genomic DNA was extracted from C.betulinus venom duct while the Bt14.10 sequence was cloned using primers designed based on the untranslated region and intron.The peptide was then synthesized using solid-phase method and folded into the target product whose disulfide bridge connection was further determined by two-step oxidative folding .Results A novel conotoxin designated as Bt 14.10 (CAHSVPGMHPCKCNNTC-NH2) was obtained,the disulfide connectivity of which was C1-C3,C2-C4.Conclusion Bt14.10 is a new A-superfamily conotoxin and has a distinct loop spacing pattern between cysteines in A-superfamily conotoxins.
4.Developmentof micromovement external fixture for treatment of bone fracture
Xiaoping WANG ; Xueguan GAO ; Xianlong ZHANG ; Zhuguo LI
Chinese Medical Equipment Journal 2003;0(12):-
The s tr ucture of a micromovement external fixture for treatment of diaphyseal long bo ne fracture is presented in this paper.Minisize DC geared motor and screw drive are used to transmit the power.Micro controller is used to control the micromove ment extent and frequency.This device can give the fractured bone ends micromo vement stress stimulation,so as to improve the forming and calcifying of the ca llus,and to accelerate the fracture healing process.This device can be applied t o the research on micromovement treatment of bone fracture.
5.Applicationof FEM to the design of medical apparatus
Xiaoping WANG ; Xianlong ZHANG ; Zhuguo LI ; Xueguan GAO
Chinese Medical Equipment Journal 1989;0(02):-
Finite element method (FEM)is a calculating method for stress and strain analysis in the field of mechanical engineering.FEM has already been used in the design of medical apparatus,especially of the fixer for fracture treatment.The external fixer taken as an example,the anti-compression,anti-blending and anti-torsion characteristics of a certain type of external fixer are analyzed using FEM.This paper shows that by using FEM,the mechanical property of medical apparatus can be revealed at the designing stage.The strength and rigidity weak pocket can be found,and thus the improvement and optimization of medical apparatus can be made.

Result Analysis
Print
Save
E-mail