1.Cyclooxygenases, lipoxygenases, their targeted drugs and the prevention of Alzheimer's disease.
Jiao-Ning SHEN ; Liu-Xin XU ; Rui WANG
Acta Pharmaceutica Sinica 2013;48(12):1743-1754
Many studies have shown that chronic inflammation occurs in the brain of patients with Alzheimer's disease (AD). It is well known that long-term administration of non-steroidal anti-inflammatory drugs (NSAIDs) can alleviate the cognitive decline of AD patient and elderly. Several inflammatory cytokines produced in the metabolism of arachidonic acid (AA) are closely related to inflammatory diseases. Lipoxygenases (LOXs) and cyclooxygenases (COXs) play a crucial role in the AA network, the products eicosanoids have an important impact on the progression of AD. Although there are many arguments and conflicting evidence, currently LOXs and COXs are still the hot topics in the research on AD pathogenesis and drug development. Here, we review the progress in research on COXs and LOXs, including their actions on CNS and their association with AD, and explore the feasibility of LOXs and COXs as targets for the drugs to prevent and/or treat AD.
Alzheimer Disease
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drug therapy
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enzymology
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prevention & control
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Amyloid beta-Peptides
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metabolism
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Animals
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Anti-Inflammatory Agents, Non-Steroidal
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pharmacology
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therapeutic use
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Arachidonic Acid
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metabolism
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Brain
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metabolism
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Cyclooxygenase 1
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metabolism
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Cyclooxygenase 2
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metabolism
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Cyclooxygenase Inhibitors
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therapeutic use
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Humans
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Lipoxygenase Inhibitors
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therapeutic use
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Lipoxygenases
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metabolism
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Prostaglandin H2
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metabolism
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Prostaglandin-Endoperoxide Synthases
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metabolism
2.FRNK inhibited hepatic stellate cells in vitro
Jiangang SHEN ; Xiaolan ZHANG ; Xiaoxia HUO ; Qinghai JIAO ; Hongfang WANG
Basic & Clinical Medicine 2006;0(11):-
Objective To investigate the effect and mechanism of FRNK on the proliferation of Hepatic Stellate Cells in vitro.Methods FRNK plasmid mediated by cationic liposome was transfected into HSCs.The proliferation of HSCs was evaluated by modified MTT assay.The level of FRNK,FAK,p-FAK(Tyr397),ERK1 and p-ERK in HSCs were assayed by Western blot and RT-PCR.Results Compared with nFRNK plasmid group,FRNK inhibited the proliferation of HSCs and the inhibition rates at 12,24 and 48 h were 20.07%,26.16% and 29.77%(P
3.Primary results of the 3-in-1 technique of Disc-FX system for the discogenic low back pain
Wei ZHANG ; Huiwang WANG ; Jiaxun JIAO ; Yunxia WANG ; Dalong YANG ; Wenyuan DING ; Yong SHEN
Chinese Journal of Orthopaedics 2011;31(10):1049-1055
ObjectiveTo investigate the clinical efficacy of the 3-in-1 technique of Disc-FX system,namely:discectomy,radiofrequency ablation and annuloplasty for discogenic low back pain in the early stage.MethodsFrom February 2010 to February 2011,40 patients with the discogenic low back pain underwent discectomy,radiofrequency ablation and annuloplasty using Disc-FX system were retrospectively analyzed,including 22 males and 18 females with an average age of 38.7 years(range,32-58 years).The visual analogue scale (VAS) scoring was applied to evaluate the back and low limb pain at preoperative,postoperative 1week,3 months,6 months,and last follow-up.The Macnab score was also evaluated at last follow-up.Results All the patients were followed up for average 13.8 months (range,6-18 months).The operative time averaged 26 min(range,20-40 min).No surgical complication was found during the follow-up.The VAS of preoperative low back pain was 6.60±1.47,VAS score of low back pain at postoperative 1 week,3 months,6 months,and final follow-up were 1.05±0.68,1.15±0.70,1.00±0.62,0.95±0.63,respectively.The postoperative VAS of low back pain decreased significantly compared with that preoperative.The VAS of preoperative limb pain was 3.05±1.23,VAS score of limb pain at postoperative 1 week,3 months,6 months,and final follow-up after operation were 1.10±0.74,1.15±0.70,1.10±0.72,0.95±0.54,respectively.The postoperative VAS of limb pain decreased significantly compared with that preoperative.The evaluation of Macnab score were excellent in 20 patients,good in 17,fair in 2,and poor in 1,suggesting an effective rate of 92.5% (37/40).Conclusion Disc-FX system,which combined three surgical technique in one procedure,provides a new choice for orthopedics to treat discogenic low back pain.It can give satisfactory clinical outcomes during a short-term followup,but the long term clinical outcomes remains unknown.
4.Cerebral protective effect of desflurane anesthesia during craniotomy
Fang LUO ; Ying SHEN ; En-zhen WANG ; Baoguo WANG ; Xiping JIAO
Chinese Journal of Rehabilitation Theory and Practice 2004;10(7):396-397
Objective To determine the cerebral protective effect of different concentrations of desflurane anesthesia during craniotomy.Methods Twenty two patients, scheduled for selective craniotomy for resections of supratentorial mass lesions, were anesthetized by inhalation of desflurane. When the concentrations of desflurane were maintained at 0.7,1.0 and 1.3 mean alveolar concentration (MAC) for 30 min during removing the tumor, venous blood samples which were drawn through internal jugular bulb were analyzed. Mean arterial pressure (MAP), heart rate (HR), and jugular bulb pressure (JBP) were recorded during the craniotomy.Results Jugular bulb oxygen saturation (SjO2) was significantly declined at 1.0 and 1.3 MAC compared with that at 0.7 MAC (P<0.05 and P<0.01 respectively). There was no significant changes in SjO2 between 1.0 and 1.3 MAC (P>0.05). MAP declined dose dependently, and decreased more significantly at 1.3 MAC (P<0.01).HR and JBP increased slightly with the raising concentration of desflurane but there were no significant changes at any MAC of desflurane (P>0.05).Conclusion Desflurane anesthesia at 1.0 MAC shows cerebral protection effect during craniotomy with stable hemodynamics and improved cerebral oxygen supply and demand.
5.Expression of interleukin-13 and its receptors in mycosis fungoides
Cheng DING ; Ping WANG ; Jiao LIU ; Zhao LI ; Liuyu LI ; Dongyin LIU ; Junhui ZHENG ; Hong SHEN
Chinese Journal of Dermatology 2017;50(4):291-294
Objective To measure the expression of interleukin-13 (IL-13) and its receptors in mycosis fungoides (MF) lesions,and to investigate their clinical significance.Methods A total of 34 paraffin-embedded specimens of MF,which was confirmed by clinical and histopathological features,immunophenotyping and/or T-cell receptor gene rearrangements,were collected from Hangzhou Third People's Hospital between January 2010 and March 2016.According to the tumor-node-metastasis (TNM) staging system,5 patients were at stage I A,9 at stage Ⅰ B,17 at stage Ⅱ A,and 3 at stage Ⅱ B.Ten normal skin tissue specimens served as controls.Immunohistochemical study was conducted to measure the expression of IL-13,IL-13Rα1 and IL-13Rα2.Results IL-13,IL-13Rα1 and IL-13Rα2 were all expressed in atypical lymphoid cells and epidermotropic lymphoid cells in MF lesions at various stages.IL-13Rα2 was highly expressed in all the MF lesions.None of IL-13 and its receptors were expressed in normal skin tissues and lymphocytes.The expression rates of IL-13 and its receptors in MF lesions increased along with the progression of MF.Additionally,the expression rates of IL-13 (10.00% ± 3.14%),IL-13Rα1 (21.43% ± 6.88%) and IL-13Ro2 (31.14% ± 6.38%) significantly decreased in MF lesions at stage Ⅰ compared with those at stage Ⅱ (27.50% ± 11.00%,39.45% ± 9.43%,44.40% ± 11.15%,respectively,all P < 0.05),but no significant differences were observed between stage Ⅰ A and Ⅰ B,or between stage Ⅱ A and Ⅱ B (P > 0.05).Conclusion IL-13 and its receptors,especially IL-13Rα2,may be expected to serve as biomarkers for early diagnosis of MF and prediction of its biological behaviors.
6.4-amino-2-trifluoromethyl-phenyl retinate induced K562 cell differentiation and cell cycle influence
Jingjing RUAN ; Feihu CHEN ; Jiao XU ; Juan SHEN ; Jingbo SHI ; Fanrong WU ; Yuan WANG
Chinese Pharmacological Bulletin 2003;0(09):-
Aim To explore the effect of 4-amino-2-trifluoromethyl-phenyl retinate(ATPR)on proliferation,differentiation activity in K562 cell line,and to research the mechanisms.Methods Cell proliferation was assessed by MTT assay.Cell differentiation index was analyzed by NBT reduction test.Morphologic changes were observed by Wright's staining in the light microscope. Cell cycle was determined by FCM.The mRNA expression of Cyclin D1,Cyclin E,CDK2,CDK4,CDK6,P21cip1,P27kip1,P57kip2,PCNA mRNA were detected by RT-PCR.While the protein expression of cyclin D1 and CDK4 was detected by Western blot.Results The growth of K562 cells was inhibited in a dose-dependent manner.NBT reduction test indicated that the ATPR could induce differentiation of K562 cells and increase the positive cell ratio.Morphologic changes were observed after Wright's staining using inverted phase contrast microscope.The proportion of cells in G0/G1 phase increased while S phase cells decreased.Cell cycle progression was blocked in the G1 phase.The expression of Cyclin E,cyclin D1,CDK2,CDK4,CDK6 mRNA decreased,while PCNA,P21 cip1,P27 kip1 change was not obvious,but P57 (kip2) mRNA expression was increased.Cyclin D1 and CDK4 protein expressions were reduced as well.Conclusions ATPR inhibits the growth of K562 cells and induces differentiation.P57 kip2 plays a key role in differentiation.Moreover,high level of P57kip2 is regulated via inhibiting its degradation through reducing proteasome-dependent proteolysis,and ATPR plays a role in cell cycle arrest.
7.A survey on current status of two-way referral among residents in Beijing communities
Chaoying QU ; Yue SHA ; Xiaoming HUANG ; Yang JIAO ; Xuejun ZENG ; Qiang SHEN ; Guili CAO ; Heping JI ; Hui WANG
Chinese Journal of General Practitioners 2011;10(8):571-573
A cross-sectional survey on two-way referral using self-report questionnaire was conducted in a sample of 1423 residents living in 4 communities in Caobeidian area, Chaoyang District and 4 communities in Dongcheng District from April to July 2009. Among the residents who responded the questionnaire, 19.7% (88/446) from Gaobeidian and 8.2% ( 80/977 ) from Dongcheng District were referred to hospitals in 2008. And 30.7 % (27/88) in Gaobeidian and 43.8% (35/80) in Dongcheng District referred to hospital based on their own decision rather than doctors' recommendation; 45. 5% (40/ 88) in Gaobeidian and 45. 0% (36/80) in Dongcheng District of referrals were officiary processed by health institutions. The survey also showed that 57.6% and 59.4% of the respondents from the two districts preferred to free referral between community health service centers and hospitals.
8.Clinical application of stent-graft for the treatment of aneurysm,preliminary result of 71 cases
Xiaoming ZHANG ; Xuemin ZHANG ; Wei LI ; Qingle LI ; Jingjun JIANG ; Yang JIAO ; Chenyang SHEN ; Lian YUAN ; Zhonggao WANG
Chinese Journal of General Surgery 1993;0(03):-
ObjectiveTo summarize our preliminary result of the management of aneurysm using stent-graft. Method Different types of aneurysm were treated by stent-grafting in 71 cases including dissecting aortic aneurysm in 48 cases,infrarenal abdominal aortic aneurysm in 13 cases,pseudoaneurysm in descending aorta or left subclavian artery or infrarenal abdominal aorta and suprarenal abdominal aorta in 4,1,2 and 1 case(s) respectively,left or right iliac aneurysm in 2 cases respectively. The proximal intimal entry for dissecting aortic aneurysm and rupture site for pseudoaneurysm were sealed. Abdominal aortic aneurysm or iliac aneurysm was excluded using bifurcated or aorto-uni-iliac or straight stent-graft. Results The technique was successful in all cases. Two patients died perioperatively. Slight leakage in the proximal end of the dissecting aortic aneurysm was found in 5 cases,the leakage sealed off in 4 cases half year later. The reflux from distal entry was present in 9 cases. Initial leakage found in 6 cases of the abdominal aortic aneurysm,underwent spontaneous healing in 5 cases when followed-up at 3 months. Conclusion The treatment of dissecting aortic aneurysm,pseudoaneurysm and abdominal aortic aneurysm using stent-graft is mini-invasive and safe,though the long-term efficacy remains to be clarified.
9.Analysis of time trend of hepatocellular carcinoma mortality in Haimen city of Jiangsu province from 1993 to 2006
Jiao-Feng WANG ; Wen-Yao LIN ; Feng JIANG ; Wei MENG ; Fu-Min SHEN
Chinese Journal of Epidemiology 2010;31(7):727-732
Objective To predict the trend of hepatocellular carcinoma (HCC) mortality and investigate the features of its mortality including age, period, and birth cohort in males living in Haimen city of Jiangsu province, China. Methods Grey model (GM) was modeled using standardized mortality rate (SMR) of HCC from 1993 to 2006, and was applied to predicting SMR until 2012. Based on the mortality density (MD) for a four-year period, the goodness-of-fit of models and comparisons between models were evaluated so as to obtain the best one among these models including the effects of intercept, age-period-cohort (APC) , age-period (AP), age-cohort (AC),period-cohort(PC), and APC. Both APC full model and the best model were used to estimate effects of age, period, and cohort on HCC mortality. In addition, MD from 2005 to 2012 was predicted by the best model. Results Predictions based on GM (1,1 )showed that SMR was 48.578 per 100 000 population (relative error=-1.267% ) in 2007 year, which declined between 2008 and 2012. The lowest value was 45.578 per 100 000 people (in the 2012 year). The results of fitted models and comparisons between models showed that AP model was the best one (△G2=9.065,AIC=202.544). The curvatures of the effects of the three factors from APC model suggested that significances existed in changes of curvatures of 36.5-40.5 years old- (-0.368) and 64.5-68.5 years old-(-0.489) as well as in the change of 1956-1959 birth cohort (C21949.5. 1967.5=-0.492). The estimation of relative risks for AP model showed that the age effects were upward to 64.5-68.5 years old-, then downward; and that the period effects were found to be declined between 1993 and 2004. Predictions based on AP model suggested the decrease of HCC mortality. Conclusion The slightly decreasing trend of HCC mortality for males might be explained by age, period and a minor birth cohort effects in Haimen of China.
10.Analysis of relationship of HBV PreS1 antigen, anti-HBc IgM, DNA load and genotypes in hepatitis B patients.
Wang-Sen QIN ; Li-Ping SHEN ; Shuang ZHANG ; Wen-Jiao YIN ; Fing WANG
Chinese Journal of Experimental and Clinical Virology 2012;26(5):328-330
OBJECTIVETo explore the relationship of HBV PreS1 antigen, anti-HBc IgM, DNA load and genotypes, and the significance for clinical diagnosis and prognostic.
METHODSEnzyme linked immune-sorbent assay was used to test the HBV serum markers of HB patients; HBV-DNA copies was detected by time fluorescence quantitative PCR; using nested PCR to amplify the S fragment of HBV genome, then sequence and make blast with HBV standard sequences to ascertain genotypes. Make comprehensive analysis of these indexes.
RESULTS355 serum specimens of acute or chronic HB patients were collected. The positive rates of HBV PreS1-Ag and HBV-DNA in model I (positive for HBeAg) were 80.2% and 73.7% respectively, which both higher than other models. The abnormal rate of ALT and AST were higher in PreS1-Ag positive group than negative, as well as in anti-HBc IgM positive group. There are 4 samples is genotype B (2.9%), 76 genotype C (55.9%) and 56 genotype D (41.2%). Positive rate of HBeAg and HBV-DNA of genotype C samples were both higher than which of genotype B and D.
CONCLUSIONPreS1-Ag and Anti-HBe-IgM indexes are of great value to viral hepatitis B early diagnosis, HBV replication surveillance and prognostic evaluation; the major HBV genotypes in Henan province are C and D, and the positive rate of HBeAg and HBV-DNA were both higher in genotype C HBV infection population than genotype B and D.
Adolescent ; Adult ; Aged ; DNA, Viral ; blood ; Female ; Genotype ; Hepatitis B ; immunology ; virology ; Hepatitis B Antibodies ; blood ; Hepatitis B Core Antigens ; immunology ; Hepatitis B Surface Antigens ; blood ; Humans ; Immunoglobulin M ; blood ; Male ; Middle Aged ; Protein Precursors ; blood ; Viral Load ; Virus Replication