1.Association of CMTM5 gene expression with the risk of in-stent restenosis in patients with coronary artery disease after drug-eluting stent implantation and the effects and mechanisms of CMTM5 on human vascular endothelial cells.
Teng Fei LIU ; Tao LIN ; Li Hui REN ; Guang Ping LI ; Jian Jun PENG
Journal of Peking University(Health Sciences) 2020;52(5):856-862
OBJECTIVE:
To elucidate the correlation between CKLF-like marvel transmembrane domain containing member (CMTM5) gene and the risk of in-stent restenosis (ISR) with coronary artery disease (CAD) patients and to detect the effects and mechanisms of CMTM5-stimulated genes on human vascular endothelial cells (ECs) proliferation and migration.
METHODS:
A total of 124 hospitalized patients in Shijitan Hospital were enrolled in this study. All the CAD patients were detected with platelet reactivity and grouped into two groups according to platelet reactivity; ISR was conformed by coronary angiography; RT-PCR method was used to detect CMTM5 gene expression; The CMTM5 over expression, reduction and control EC lines were established; Cell count, MTT, Brdu and flow cytometry methods were used to detect the proliferation of ECs, scratch and transwell experiments to test the migration of ECs, Western blot was used to detect signal path expressions.
RESULTS:
CMTM5 gene expression in HAPR (High on aspirin platelet reactivity) group was 1.72 times compared with No-HAPR group, which was significantly higher than No-HAPR group. HAPR group ISR rate was 25.8% (8 cases), the incidence of No-HAPR ISR group was 9.7% (9 cases), and the results showed that in HAPR group, the incidence of ISR was significantly higher than that in No-HAPR group (P=0.04, OR=0.04, 95%CI=1.16-7.52), which showed that CMTM5 gene was significantly correlated with the risk of ISR. In HAPR group ISR rate was 25.8% (8 cases), the incidence of ISR in No-HAPR group was 9.7% (9 cases), and the results showed that the risk of ISR in HAPR group was significantly higher than that in No-HAPR group. All the results showed that CMTM5 was significantly correlated with the risk of ISR in CAD patients (P < 0.05). CMTM5 overexpression inhibited the proliferation and migration ability of ECs (P < 0.05), PI3K/Akt signaling pathways were involved in the role of regulation on ECs.
CONCLUSION
Our results revealed that CMTM5 gene was closely related with ISR, CMTM5 overexpression may repress ECs proliferation and migration through regulating PI3K-Akt signaling.
Chemokines
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Coronary Artery Disease/surgery*
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Coronary Restenosis
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Drug-Eluting Stents/adverse effects*
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Endothelial Cells
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Humans
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MARVEL Domain-Containing Proteins
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Phosphatidylinositol 3-Kinases
;
Tumor Suppressor Proteins
2.Association between CMTM5 gene and coronary artery disease and the relative mechanism.
Teng Fei LIU ; Tao LIN ; Li Hui REN ; Guang Ping LI ; Jian Jun PENG
Journal of Peking University(Health Sciences) 2020;52(6):1082-1087
OBJECTIVE:
To elucidate the correlation between CKLF-like MARVEL transmembrane domain containing member 5 (CMTM5) gene and the risk of coronary artery disease (CAD), and to detect the effects of CMTM5 gene expression changes on the ability of adhesion and migration of THP-1 cells.
METHODS:
Using case-control method, a total of 700 hospitalized patients in Shijitan Hospital were enrolled in this study. CAD were diagnosed by coronary angiography, which was defined as at least one blood vessel diameter stenosis ≥50% according to the result of coronary angiography. Reverse transcription-polymerase chain reaction (RT-PCR) method was used to detect CMTM5 gene expression; enzyme linked immunosorbent assay (ELISA) method to detect the plasma level of CMTM5; and Logistic regression to analyze CMTM5 genes and the risk of CAD. Human vascular endothelial cells (ECs) and THP-1 cells were cultivated, adhesion and Transwells experiments were used to evaluate the chemotactic capabi-lity of CMTM5 gene on THP-1 cells.
RESULTS:
In this study, 350 CAD patients matched with 350 control patients were included. RT-PCR results revealed CMTM5 mRNA expression in CAD group was 3.45 times compared with control group, which was significantly higher than that in control group (P < 0.05). The levels of CMTM5 plasma protein in CAD group was (206.1±26.9) μg/L, which was significantly higher than that in control group (125.3±15.2) μg/L (P < 0.05). After adjusted for the risk factors of age, gender, BMI, smoking, hypertension, diabetes and hyperlipidemia, Logistic regression analysis results indicated that CMTM5 was the susceptibility factors of CAD, which still had significant correlation with CAD (P < 0.05). Adhesion and Transwells experiments results revealed that the numbers of adhesion and migration of THP-1 cells in CMTM5 overexpression ECs group (EO group) were significantly higher than that in lenti-mock infected ECs group (EO-MOCK group), non-infected ECs group (EN group), lenti-mock infected ECs group (ES-MOCK group), and CMTM5 suppression ECs group (ES group). On the contrary, the numbers of adhesion and migration of THP-1 cells in ES group were significantly lower than that in the other four groups (P < 0.01).
CONCLUSION
CMTM5 gene was closely related to the development of CAD. CMTM5 overexpression promoted the adhesion and migration of THP-1, which might play a part in the mechanisms of atherosclerosis and CAD.
Chemokines
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Coronary Angiography
;
Coronary Artery Disease/genetics*
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Endothelial Cells
;
Humans
;
MARVEL Domain-Containing Proteins
;
Tumor Suppressor Proteins
3.A novel HIF-1 inhibitor--manassantin A derivative LXY6099 inhibits tumor growth.
Fang-Fang LAI ; Xiao-Yu LIU ; Fei NIU ; Li-Wei LANG ; Ping XIE ; Xiao-Guang CHEN
Acta Pharmaceutica Sinica 2014;49(5):622-626
Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor on hypoxia responses in mammalian tissues. HIF-1 plays as a positive factor in solid tumor and leads to hypoxia-driven responses that enhance its downstream gene expression for tumor growth and survival. LXY6099 was obtained by the structural modification and optimization of manassantin A (MA) as a high potent HIF-1 inhibitor. Antitumor activity of LXY6099 was observed in this study. LXY6099 with an IC50 value of 2.46 x 10(-10) mol x L(-1) showed more sensitive inhibition activity to HIF-1 than that of MA detected by reporter gene assay (> 100 folds). It showed strong inhibition on the growth of human solid tumor cell lines. Furthermore, LXY6099 exhibited significant antitumor activity against established human tumor xenografts in nu/nu mice with treatment of MX-1 breast cancer. Thus, LXY6099 as a novel HIF-1 inhibitor could be further developed into anti-cancer agents.
Animals
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Antineoplastic Agents
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pharmacology
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Breast Neoplasms
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metabolism
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Cell Line, Tumor
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Gene Expression Regulation, Neoplastic
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Heterografts
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Humans
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Hypoxia-Inducible Factor 1
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metabolism
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Lignans
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pharmacology
;
Mice, Nude
4.Structure Modeling of Azoreductase AZR and Site-directed Mutagenesis of Its K~(109) Residue
Guang-Fei LIU ; Ji-Ti ZHOU ; Mi ZHOU ; Jing-Mei LI ;
Microbiology 1992;0(05):-
Three-dimensional structure model of azoreductase AZR of Rhodobacter sphaeroides was con- structed using homology modeling method. It is a flavodoxin adopting ?/? structure. Structure alignment of two different types of flavin-dependent azoreductases revealed that they possessed high similarity. Based on sequence and structure analysis, site-directed mutagenesis of K109H and K109A were performed. The opti- mal pH values are pH 6 and pH 9 for K109H and K109A mutant protein, respectively. The optimal tempera- ture (30℃) is not affected by mutagenesis. Positively charged residues at position 109 is necessary for the binding of methyl red, while K109H is not a conserved mutagenesis for the binding of NADPH. K109 may only be involved in the binding of the 2’-phosphate group of NADPH and have no effect on the binding of NADH.
5.Decoration reconstruction for finger defect in emergency
Ji-Hui JU ; Rui-Xing HOU ; Yue-Fei LIU ; Qiang ZHAO ; Lei LI ; Guang-Zhe JIN ;
Chinese Journal of Microsurgery 2006;0(06):-
Objective To discuss methods of decoration reconstruction for finger defect in emergency and to observe the elinical effects.Methods Of the 41 cases of finger injuries of different degrees,15 were repaired with part of the skin flaps of the big toenails or skin flaps of the second toenalis,8 were repaired with part of the skin flaps of the big toenails,7 were reeonstructed with the second tiptoes,11 were repaired with the abdominal skin flaps of the big toes or lateral flaps of the second toes.Results All the 41 fingers sur- vived.One skin flap of the big toe was somewhat swelling and a decorating operation was performed.The 4~18 months of follow-up visitation of the rest cases revealed good function and shapes.No obvious functional ab- norality was found in the donating feet.Conclusion Various kinds of decoration reeonstruetion for finger defects are available to recover the hand shape and function as much as possible.
7.Endoscopic surgery for hypertensive cerebral hemorrhage.
Zhi-fei WANG ; Fei LIU ; Da-guang LIAO ; Tian-yi ZHANG
Journal of Central South University(Medical Sciences) 2005;30(4):424-426
OBJECTIVE:
To evaluate the use of endoscopic surgery for hypertensive cerebral hemorrhage.
METHODS:
Sixteen patients with hyertensive intracerebral hematoma were evacuated with neuroendoscope. The surgical invasive markers, volume of remaining hematoma, and prognosis were compared with those of 19 comparable patients undergoing conventional craniotomy.
RESULTS:
Complete evacuation of hematoma was achieved in 9 patients, and partial evacuation in 7. All patients were followed up for 6 months. According to GOS, the result was excellent in 6 patients, good in 6, fare in 2, poor and dead in one respectively. The volume of remaining hematoa and invasive markers significantly decreased (P < 0.05); No difference was found in prognosis between the two groups (P > 0.05).
CONCLUSION
Neuroendoscopic surgery for hypertensive intracerebral hematoma is characterized by mini-invasion, time-saving, and direct-vision, and is a new approach in this field.
Adult
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Aged
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Female
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Follow-Up Studies
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Hematoma
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surgery
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Humans
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Intracranial Hemorrhage, Hypertensive
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surgery
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Male
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Middle Aged
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Neuroendoscopy
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Neurosurgical Procedures
8.CT angiography-based simulation of the surgical approach in early operation for ruptured aneurysm.
Zhi-fei WANG ; Da-guang LIAO ; Tian-yi ZHANG ; Jin-fu YANG ; Fei LIU
Journal of Southern Medical University 2009;29(12):2492-2496
OBJECTIVETo simulate the surgical approaches for intracranial aneurysms using three-dimensional CT angiography (3D-CTA) and assess the value of 3D-CTA in early microneurosurgery for ruptured intracranial aneurysms.
METHODSForty-eight patients with spontaneous subarachnoid hemorrhage due to ruptured intracranial aneurysm were confirmed by early operation. All the patients were classified according to Hunt-Hess, including 11 of grade I, 29 of grade II, and 8 of grade III. CTA was performed before the operation and surgical simulation was conducted. The preoperative findings on CTA and the intraoperative findings were compared and the clinical value of cerebral 3D-CTA was analyzed.
RESULTSPre-operative 3D-CTA clearly displayed the location, size and shape of the aneurysms, the axis direction of the aneurysm apex and the width of aneurysm neck. The spatial relation between the parent aneutysm artery, the aneurysm, the peripheral vessels and the bony structures were also demonstrated. These findings were basically consistent with the intraoperative findings. The Glasgow outcome score was 5 in 41 patients, 4 in 4 patients, 3 in 2 patients, and 2 in 1 patient upon discharge from the hospital.
CONCLUSIONSPreoperative 3D-CTA examination can simulate the surgery for ruptured aneurysms to help improve the surgical success rate.
Adult ; Aged ; Aneurysm, Ruptured ; diagnostic imaging ; surgery ; Cerebral Angiography ; methods ; Computer Simulation ; Female ; Humans ; Imaging, Three-Dimensional ; Intracranial Aneurysm ; diagnostic imaging ; surgery ; Male ; Middle Aged ; Radiography, Interventional ; Subarachnoid Hemorrhage ; diagnostic imaging ; etiology ; surgery ; Tomography, Spiral Computed
9.Hydroxyphthalimide induced medicamentosa-like dermatitis in five patients.
Jian-fang ZOU ; Shao-qiu SUN ; Yan-fei LI ; Yu-jun ZHAO ; Yan-qing PEI ; Guang-feng LIU
Chinese Journal of Industrial Hygiene and Occupational Diseases 2006;24(10):625-625
Adult
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Dermatitis, Occupational
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etiology
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Drug Eruptions
;
etiology
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Humans
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Male
;
Phthalimides
;
adverse effects
10.Complete Genomic Sequence of a Chinese Isolate of Duck Hepatitis Virus
Guang-qing, LIU ; WANG, FEI ; NI, ZHENG ; YUN, TAO ; YU, BIN ; Jiong-gang, HUANG ; Jian-Ping, CHEN
Virologica Sinica 2007;22(5):353-359
The complete genomic sequence of Duck hepatitis virus 1 (DHV-1) ZJ-V isolate was sequenced and determined to be 7 691 nucleotides (nt) in length with a 5'-terminal un-translated region (UTR) of 626 nt and a 3'-terminal UTR of 315 nt (not including the poly(A) tail). One large open reading frame (ORF) was found within the genome (nt 627 to 7 373) coding for a polypeptide of 2 249amino acids. Our data also showed that the poly (A) tail of DHV-1 has at least 22 A's. Sequence comparison revealed significant homology (from 91.9% to 95.7%) between the protein sequences of the virus in the Picornaviridae family, its genome showed some unique characteristics. DHV-1 contains 3copies of the 2A gene and only 1 copy of the 3B gene, and its 3'-NCR is longer than those of other picornaviruses. Phylogenetic analysis to do sequence homology based on the VP1 protein sequences showed that the ZJ-V isolate shares high sequence homology with the reported DHV-1 isolates (from 92.9% to 99.2%), indicating that DHV-1 is genetically stable.