1.Aspirin inhibition of expression of inflammatory proteins induced by oxidized low-density lipoprotein in HUVECs
Wei WU ; Ruomei QI ; Rui LI ; Xin GAO ; Li BAO
Chinese Pharmacological Bulletin 1986;0(04):-
Aim To evaluate the effects of aspirin on the expression of inflammatory proteins induced by oxidized low-density lipoprotein(ox-LDL) in human vascular endothelial cells (HUVECs). Methods HUVECs were stimulated with different concentrations of ox-LDL. The expression of inflammatory proteins was detected by Western blot.Intracellular ROS generation was measured by flow cytometry using perexide-sensitive flurscent probe 2′, 7′-dichrofluorescein diacetate(DCFH-DA).Results ① Aspirin inhibited COX-2 expression induced by ox-LDL. Cells were preincubated with 2.5 mmol?L-1, 5 mmol?L-1 of aspirin or without any treatment for 30 min and then stimulated by 0.3 g?L-1 ox-LDL for 16 h, COX-2 expression was reduced by treating of aspirin.COX-2 expression was enhanced after the stimulation with ox-LDL, and aspirin inhibited the increasing.② Aspirin suppressed ICAM-1 expression induced by ox-LDL in HUVECs. ICAM-1 expression was increased by ox-LDL stimulation for 16 h, and aspirin significantly down-regulated the expression. Similar results were obtained by immunofluorescence.③ Aspirin partially reduced ROS production induced by ox-LDL in HUVECs. After stimulation with 0.3 g?L-1 ox-LDL for 16 h, the intracellular level of ROS was increased, however, aspirin failed to fully inhibit the phenomenon.Conclusion Nonsteroidal anti-inflammatory drugs (NSAID) aspirin significantly down-regulated the expression of COX-2 and ICAM-1 induced by ox-LDL.The results suggested that aspirin could reduce the inflammation responses mediated by ox-LDL on HUVECs in atherosclerosis.
2.Relationship between appositional angle closure and darkroom provocative test in fellow eyes of acute primary angle closure after laser peripheral iridotomy
Bao-qun, YAO ; Ling-ling, WU ; Chun, ZHANG ; Xin, WANG
Chinese Journal of Experimental Ophthalmology 2012;30(2):155-159
BackgroundLaser peripheral iridotomy(LPI) can break the pupillary block,and is an effective method of treating acute primary angle closure (APAC).However,a part of APAC eyes may gradually develop a formation and extension of peripheral anterior synechia(PAS) and increased intraocular pressure(IOP) after LPI.ObjectiveTo investigate the relationship between appositional angle closure and darkroom provocative test(DRPT) in the fellow eyes with APAC after LPI.Methods Fellow eyes of APAC without PAS after LPI were studied.Ultrasounic biomicroscopy(UBM) were performed in darkness to observe whether appositional angle closure occurred and compare the relationship between the quadrants with appositional angle closure and the results of DRPT.Results Fifty-four patients were included in the study.Appositional angle closure was observed in at least one quadrant in 20(37.0% ) of the 54 fellow eyes with APAC after LPI.Fifty-one patients were given DRPT and positive result in 9 patients( 17.6% ).According to the quadrants with appositional angle closure,there were 5 patients with DRPT positive results in 46 patients with appositional angle closure 0 to 2 quadrants,and 4 patients with DRPT positive results in 5 patients with appositional angle closure 3 to 4 quadrants ( P =0.003 ).Bivariate correlation analysis indicated a positive correlation between the value of the increased IOP in DRPT and the number of quadrants with appositional angle closure in darkness( r =0.397,P =0.004).ConclusionsA certain proportional fellow eyes of APAC appeared appositional angle closure in darkness and DRPT positive result after LPI.The more the quadrants of appositional angle closure after LPI,the greater the likelihood of a positive DRPT.It suggests that the APAC fellow eyes and attack eyes with the same anatomical configuration still have the possibility of angle closure after LPI,and need follow-up and treatment for a long time.
3.A clinical study on indomethacin for prevention of heterotopic ossification following surgical treatment of acetabular fractures
Shi-Wen ZHU ; Man-Yi WANG ; Xin-Bao WU ;
Chinese Journal of Orthopaedic Trauma 2004;0(07):-
Objective To investigate the effect of indomethacin on prevention of heterotopic ossification (HO)after operative treatment of acetabular fractures.Methods Fifty patients with acetabular fractures received in our department operative treatment through Kocher-langenbeck(K-L)approach and oral administration of in- domethacin afer operation from February 2001 to August 2003.Forty-eight of them were successfully followed up for incidence of HO and their clinical functions were assessed.The results were compared with those of 40 patients who had been treated with the same operative procedures but without oral administration of indomethacin in our depart- ment from March 1993 to May 1998.The patients who could not tolerate the drug were not included.Results The follow-ups averaged 22.8 months(range,6 to 39 months).HO occurred in eight cases.The incidence of HO was 16.7%(8/48).According to Brooker evaluation of HO,five cases were rated as degreeⅠ,three as degreeⅡ, and none as degreeⅢorⅣ.The incidence of severe HO was 0.In the control group,the incidence of HO was 35.0%(14/40)and the incidence of severe HO was 10.0%(4/40).The differences were statistically significant (P<0.05).Conclusion Oral administration of indomethacin after operative treatment of acetabular fractures can inhibit HO.
4.Treatment of nonunion of humeral shaft fracture with plate fixation and bone graft
Xin-Bao WU ; Ming-Hui YANG ; Ting LI ;
Chinese Journal of Orthopaedic Trauma 2004;0(07):-
Objective To evaluate the operative treatment of nonunion of humeral shaft fracture with in- ternal plate fixation and autogenous cancellous hone graft.Methods Forty-one cases of nonunion of humeral shaft fracture operatively treated from February 2002 to December 2004 were analyzed retrospectively.There were 32 males and nine females.Their average age was 37.5 years(range,17 to 67 years).Sixteen nonunions were defined as hypertrophic and 25 as atrophic.We followed all the patients and obtained their complete medical information. Results Our average follow-up was 22.6 months(range,8 to 42 months).Forty fractures(97.6%)were united within an average of 5.8 months(range,3 to 12 months).Complications included iatrogenic radial nerve injury in three patients,wound infection in one patient and fracture nonunion in one patient.At the final follow-up,shou]der and elbow functions were found to be satisfactory.Conclusion Open reduction and plate internal fixation sup- plemented with autogenous cancellous bone graft is an effective treatment for nonunion of humeral shaft fracture.
5.Oxidative stress injury of myocardial cells induced by emphysema with intermittent hypoxia in rats
Jianmin DUAN ; Huaiyong CHEN ; Qi WU ; Xin SUN ; Jing FENG ; Xue LI ; Long XU ; Cuiping BAO
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2014;(1):22-25
Objective To observe the effect of exposure of emphysema with intermittent hypoxia on oxidative stress injury of myocardial cells in rats. Methods Sixty male Wistar rats were divided randomly into four experimental groups(each n=15). The normal control group was bred normally. The emphysema group was exposed to cigarette smoke twice a day(once 30 minutes). The intermittent hypoxia(IH)group was exposed to intermittent hypoxia circumstance 8 hours/day,and the emphysema with IH group was exposed to cigarette smoke twice a day (once 30 minutes)and intermittent hypoxia circumstance 8 hours/day. Each group was exposed for 8 weeks. At the beginning of 9 weeks,the blood gas analysis was performed in 5 rats selected randomly from each group,and the rest rats were sacrificed and their hearts and lungs were taken. Under light microscope,the lung tissues stained with hematoxylin-eosin(HE)were examined. The lung pathology and the results of blood gas analysis showed that the emphysema with IH rat model was established successfully. The levels of malonaldehyde(MDA)and superoxide dismutase(SOD)in rat myocardium were measured by enzyme-linked immunosorbent assay(ELISA),and the subunit p22phox mRNA expressions of nicotinamide adenine dinucleotide phosphate(NADPH)-oxidase were detected by real-time reverse transcription-polymerase chain reaction(RT-PCR). Results Compared with the normal group, the MDA levels and p22phox mRNA expressions were increased obviously in emphysema group, IH group and emphysema with IH group〔MDA(μmol/g):2.93±0.54, 3.58±0.63, 4.51±0.72 vs. 1.75±0.56, p22phox mRNA:0.043±0.004,0.067±0.015,0.123±0.016 vs. 0.018±0.002,all P<0.05〕,but the activities of SOD were decreased significantly(U/mg:36.07±4.79,33.51±7.12,24.29±5.36 vs. 46.08±5.12,all P<0.05). In emphysema with IH group,the increase of MDA levels and p22phox mRNA expressions and decrease of SOD levels were more remarkable compared with those in emphysema group and IH group(all P<0.05). The expression of p22phox mRNA was positively correlated with MDA level(r=0.734,P<0.001). Conclusion The myocardial tissue oxidative stress injury in rats induced by emphysema with intermittent hypoxia exposure is more serious than that induced by exposure of either emphysema or intermittent hypoxia alone,NADPH oxidase possibly being the important medium of myocardial cell response to oxidative stress.
6.Characterization of intertype specific epitopes on adenoviruses hexon.
Ting ZHANG ; Ruolei XIN ; Qin ZHANG ; Yihua BAO ; Jianxin WU
Chinese Journal of Experimental and Clinical Virology 2002;16(1):44-47
BACKGROUNDTo characterize the intertype epitopes on human adenovirus (HAdV) hexon.
METHODSBased on computerized analysis on adenoviruses sequence of genomic alignment, antigenicity prediction and 3-D structure characteristics of hexon subunit, several peptides of hexon of adenoviruses were chosen to be synthesized or recombinant proteins of the hexon were expressed in E. coli by use of PGEX-5X. To identify the existence of intertype epitopes, the antisera raised with synthetic peptides or purified recombinant proteins were analyzed with Western blot and immunofluorescent assay.
RESULTSThe results of Western blot indicated that both peptide and recombinant antibodies showed specific reactivities with hexons of HADv-3, 4, 7 individually. Meanwhile, typical stain of immunofluorescence was found on HeLa cells infected with these HAdV by incubation with peptide as well as recombinant antibodies. Also, antibodies raised against peptide recognized the recombinant hexon protein in which a corresponding region of peptides was covered.
CONCLUSIONSMost of the predicted intertype epitopes of HAdV hexon wer e exclusively found in synthetic peptides and recombinant proteins. These intertype epitopes showed to be continuous and sequential which could be employed for development of antibodies of diagnostic use.
Adenoviruses, Human ; immunology ; Amino Acid Sequence ; Animals ; Capsid ; chemistry ; immunology ; Capsid Proteins ; immunology ; Epitopes ; immunology ; HeLa Cells ; Humans ; Mice ; Peptide Fragments ; immunology
7.A case of infantile neuroaxonal dystrophy.
Ye WU ; Ying SHI ; Yun YUAN ; Xin-hua BAO ; Jiong QIN
Chinese Journal of Pediatrics 2004;42(10):796-796
8.Clinical and Electroencephalogram Characteristics of Children with Electrical Status Epilepticus during Sleep
shuang, ZHANG ; xin-hua, BAO ; xiao-yan, LIU ; jiong, QIN ; xi-ru, WU
Journal of Applied Clinical Pediatrics 1992;0(05):-
Objective To investigate the clinical and electroencephalogram (EEG) characteristics of children with electrical status cpilepticus during sleep (ESES), and the response to medication therapy. Methods AEEG and VEEG including an entire sleeping c-ycle were performed on 26 patients with ESES. The clinical and EEG changes, neuropsychological impairment and the response to medication therapy were followed up. Results Twenty five patients had seizures,21 cases had normal psychomotor development before ESES. After the onset of the disease,Fifteen cases developed language disorder, 16 cases developed psychological and behavior abnormalities, 13 cases had both of the problems Seventeen patients belonged to epileptic syndrome. Patients in this cohort had good response to clonazepam and valproate treatment. Cortical steroid could dispel the electrical discharge. Eighteen patients had been followed up. Seizures stopped in 15 cases after treatment ESES disappeared in 16 cases, 4 of them still had neuropsychological impairment ESES sustained in 2 cases Conclusions ESES is a specific EEG phenomenon. Continue epileptic form discharge during non - rapid cye movement sleep is the major cause of neuropsychological impairment in patients with ESES. To control the seizures and electrical state are very important for the prevention and treatment of neuropsychological impairment.
9.Initial Clinical and Imaging Characteristics of Basal Ganglia Germinoma in Children
xing-zhi, CHANG ; ye, WU ; xin-hua, BAO ; yue-hua, ZHANG ; jiong, QIN
Journal of Applied Clinical Pediatrics 2006;0(14):-
Objective To explore the initial clinical and imaging characteristics of basal ganglia germinoma in children.Methods Four patients with basal ganglia germinoma were reported.Their clinical features,laboratory findings,radiological manifestations,treatment and outcome were analyzed.They recieved radiation therapy and chemotherapy after diagnosis.All patients were clinically diagnosed,according to the results of low-dose cranial irradiation.The outcomes were followed up for 2 years.Results All patients were male and school-aged(9-13 years) children.The course of the disease ranged from 5 to 13 months.All patients were presented with slowly progressive hemiparesis,and 2 cases of them were presented with cognitive decline and psychosis.Seizure occurred in 2 patients.The serum ?-human chorionic gonadotropin(?-hcG) level was significantly increased in 2 patients(30.16 IU/L and 77.85 IU/L,respectively),and mildly elevated in 1 patient(4.29 IU/L),while serum ?-hcG level in another case was within normal control range.MRI demonstrated mildly high intensity in the left or right basal ganglia on T1-weighted and T2-weighted images without remarkable occupying lesion.Ipsilateral hemiatrophy of the hemisphere and midbrain was also noted.Inhomogeneous Gd-DTPA enhancement was observed.All patients had been treated with radiation therapy and chemotherapy.During 2 years follow up,significant improvement was observed in all patients after therapy,imaging lesions disappeared and the elevated ?-hcG level of those elevated before therapy returned to normal.Conclusions Early diagnosis and treatment for basal ganglia germinoma are critically important to improve the prognosis.In young male patients with progressive hamiparesis,basal ganglia germinoma should be considered for differentiation,if abnormal high intensity signals in basal ganglia on T1-weighted and T2-weighted image with ipsilateral hemiatrophy of the hemisphere are demonstrated on MRI,even without occupying effect.
10.Recent progress in targeting degradation of FAK based on PROTAC
Ying-ruo XU ; Qin-song ZHANG ; Jing-yi WU ; Run-fei BAO ; Shen-xin ZENG
Acta Pharmaceutica Sinica 2021;56(6):1571-1579
Local focal adhesion kinase (FAK) is a non-receptor intracellular tyrosine kinase that plays an important role in tumor initiation, development, metastasis and invasion, and is considered to be an important target for the development of antineoplastic drugs. It has both kinase-dependent and non-kinase-dependent scaffolding functions. However, traditional small molecular inhibitors can only inhibit its kinase-dependent activity, so it is difficult to target the kinase-independent scaffolding function. Therefore, there is an urgent need for novel strategies to enhance FAK targeting to lay the foundation for determining the druggability and discovery of FAK inhibitors. Proteolysis targeting chimera (PROTAC) is a new drug development strategy that can recruit E3 ligase to specifically ubiquitinylate target proteins for degradation through the proteasome system. The unique mechanism of action of the PROTAC system could be used to target and degrade the FAK protein, thus eliminating the scaffolding function of FAK. In this review, FAK protein, the signaling pathway, and small molecule inhibitors are briefly described, and the latest research progress in targeting the degradation of FAK using PROTAC technology is summarized.