1.Lentivirus-mediated shRNA interference targeting ADAM17 down-regulates MMP-9 expression in airway epithelial cells via TNF-α/NF-κB signaling
Jianping YAN ; Yaqing LI ; Hui ZHONG ; Chun CHEN ; Chao GU
Chinese Pharmacological Bulletin 2014;(4):559-565
Aim To study the role of TNF-α/NF-κB signaling in matrix metalloproteinase ( MMP)-9 expres-sion induced by lipopolysaccharide ( LPS ) in airway epithelial cells, and to investigate the effects of lenti-virus mediated RNAi targeting a disintegrin and metal-loproteinase 17 ( ADAM17 ) gene on MMP-9 expression induced by LPS. Methods The ADAM17 siRNA ex-pression vector was constructed, and packaged to re-combinant lentivirus in 293T cells. The HBE4-E6/E7 cells were pretreated for 30 min by NF-κB inhibitor ( PDTC) and a recombinant human TNFR p75-Fc fu-sion protein ( Etanercept) , or infected by the recombi-nant lentivirus for 72 h, and then stimulated for 24 h by LPS or TNF-α. The release of TNF-α was detected by ELISA. The mRNA and protein levels of MMP-9 were analyzed respectively by RT-PCR and Western blot. NF-κB activity was detected by electrophoretic mobility shift assay. Results LPS and TNF-α signifi-cantly increased MMP-9 mRNA and protein expressions and the activation of NF-κB in HBE4-E6/E7 cells ( P<0. 05 ) . Etanercept and PDTC significantly inhibited MMP-9 expression and the activation of NF-κB induced by LPS ( P<0. 05 ) . Lentivirus mediated RNAi targe-ting ADAM17 significantly decreased TNF-α produc-tion, inhibited MMP-9 mRNA and protein expressions and the activation of NF-κB induced by LPS in HBE4-E6/E7 cells ( P <0. 05 ) . Lentivirus mediated RNAi targeting ADAM17 did not inhibit MMP-9 mRNA and protein expressions and the activation of NF-κB in-duced by TNF-α ( P>0. 05 ) . And PDTC significantly inhibited MMP-9 mRNA and protein expressions and the activation of NF-κB induced by TNF-α ( P <0. 05 ) . Conclusions TNF-α/NF-κB signaling partic-ipates in the regulation of MMP-9 expression induced by LPS in airway epithelial cells, and lentivirus-media-ted RNAi targeting ADAM17 plays an important role in that signaling pathway upstream by regulating TNF-αrelease.
2.Pregnant women serum microR-423 as a biomarker for non-invasive prenatal diagnosis of fetal neural tube defect
Hui GU ; Tianchu HUANG ; Yan MEI ; Zhengwei YUAN
International Journal of Pediatrics 2015;42(3):331-333,337
Objective The discovery of microRNA (miRNA) in maternal serum has opened up new possibilities for non-invasive prenatal diagnosis.However,our understanding of these pregnancy-related miRNA in the serum of pregnant women with fetuses with neural tube defects (NTDs) is still limited.This article is to study the dysregulated expression of microRNA-423 (miR-423) in the serum of pregnant women with neural tube defect(NTD) fetuses and its potential role as a biomarker for non-invasive prenatal diagnosis of fetal NTD.Methods Thirty-three pregnant women whose fetuses were diagnosed as neural tube defects by ultrasound (22 cases of spina bifida and 11 cases of anencephaly)and 33 normal pregnant women were selected.Peripheral venous blood of each pregnant woman was obtained early in the morning,the serum was purified from blood by centrifugation,then total RNA was isolated from serum and the miR-423 levels were detected by real-time RT-PCR.The ROC curve was used for assessing the diagnostic accuracy of miR-423 for fetal NTD.Results We revealed miR-423 with signifcant down-regulation in expression in serum of pregnant women with NTD fetuses (0.96 ±0.14) compared as women with normal pregnancies(2.28 ±0.43) (P <0.05).We performed ROC analysis of data from the 33 case-control pairs.The expression of miR-423 could distinguish NTD cases from normal controls,with an AUC of 0.711 (95 % CI:0.566 ~ 0.856) (P < 0.05).Moreover,the expression of miR423 decreased only in serum of pregnant women with anencephaly fetuses(0.58 ±0.08)by the analysis in different forms of NTD.Conclusion miR-423 is deregulated in the serum of pregnant women with NTD fetuses and highlight the clinical potential of miR-423 as biomarker for diagnosis and prognostication of fetal NTD.
3.The role of phosphorylated protein kinase R-like ER kinase in brain tissue of hypoxic-ischemic neonatal rats and the following effect on neuronic apoptosis
Hui GU ; Lian JI ; Tianchu HUANG ; Yan MEI ; Zhengwei YUAN
Chinese Pediatric Emergency Medicine 2015;22(5):316-319
Objective To investigate the effect and mechanism of phosphorylated protein kinase R-like ER kinase(p-PERK) and C/EBP homologous protein(CHOP) after hypoxic-ischemic brain damage ( HIBD) . Methods Neonatal 7-day-old Sprague Dawley rats were divided into sham-operation control group and HIBD group( n=30 per group) . Each group was divided into 0 h,6 h and 24 h subgroup after operation ( n=10 per group) . The ratio of apoptosis of brain cell was measured by flow cytometer and the expression of p-PERK and CHOP were detected by Western blot. Results (1)Apoptosis cell appeared at 6 h in HIBD group,the ratio of cell apoptosis was(2. 17 ± 0. 19)%. The apoptosis cell obvious increased at 24 h,the ratio of cell apoptosis was(13. 42 ± 0. 83)%. There was a significant increase in the ratio of apoptosis after HIBD 6 h and 24 h, as compared with sham-operation control group [ ( 0. 57 ± 0. 06 )%( P <0. 01 ) ] . ( 2 ) The expression of both p-PERK and CHOP was very low in sham-operation control group. In the HIBD group,the expression of both p-PERK and CHOP began to increase at 6 h and increased furthermore at HIBD 24 h. The differences in the expression levels of p-PERK and CHOP in HIBD group among different time points were significant( P<0. 01 ) . ( 3 ) The expression of p-PERK positively correlated with the expression of CHOP (r=0. 997,P< 0. 05). Conclusion With the emerging of apoptosis after HIBD,the expression of both p-PERK and CHOP increases. The imbalance in the expression of PERK induces the apoptosis of brain cells in the HIBD of neonatal rats by regulation of CHOP expression.
4.Effects of the spinal cord intrathecal injected to agmatine on intrathecal morphine analgesia.
Zhong-Ping LAN ; Ya-Hui CHEN ; Nan GU ; Li-Ze XIONG ; Yan-Yuan SUN
Chinese Journal of Applied Physiology 2014;30(3):197-203
Agmatine
;
administration & dosage
;
pharmacology
;
Analgesia
;
methods
;
Animals
;
Injections, Spinal
;
Male
;
Morphine
;
pharmacology
;
Rats
;
Rats, Sprague-Dawley
;
Spinal Cord
;
drug effects
5.Analysis of TCM Injections in the Inpatients from 4 Hospitals of Jiading District in Shanghai
Fang QIAN ; Yan GU ; Hui SHEN ; Zhiqiang ZHOU ; Yinghua WANG ; Yushu GUO ; Kouming TANG
China Pharmacy 2015;(29):4038-4040
OBJECTIVE:To provide reference for rational use of TCM injections. METHODS:Among the inpatients who used TCM injections in 4 hospitals of Shanghai Jiading district in 2013,100 cases were collected by systematic sampling in each hospital separately, and the data were analyzed retrospectively. RESULTS:The varieties and amount of TCM injections for blood-activating and stasis-resolving both occupied the first place. 22% inpatients used two or more TCM injections at the same time. The proportion of overdose use of TCM injections reached 54.55%. The type of unreasonable drug use mainly included drug use against differentiation of syndromes,super indications drugs and solvent error. Combined use of TCM injections with same ef-fect accounted for 20.45% of combined use of TCM injections. CONCLUSIONS:It is effective means to improve rational drug use that great impertance paid for clinical use of TCM injections.
6.Motor imagery training can improve motor function and gait after stroke
Yan LI ; Xudong GU ; Meifang SHI ; Hui LI ; Jianming FU ; Hua WU
Chinese Journal of Physical Medicine and Rehabilitation 2015;37(7):518-521
Objective To investigate the effect of motor imagery therapy based on mirror neuron theory on the motor function and gait in stroke survivors.Methods Forty-nine stroke survivors were randomly divided into a treatment group (n =24) and a control group (n =25) using a random number table.All the patients in both groups were given similar conventional rehabilitation treatment.In addition,the patients in the treatment group were given motor imagery training based on mirror neuron theory once a day for 20 min each time,5 days a week,lasting 8 weeks.The Fugl-Meyer assessment (FMA),Functional Ambulation Categories (FACs),average step length,the percentage of time spent on the intact foot and the paralyzed foot,and 6 minute walking distance were used to evaluate the subjects' motor function and gait before and after 8 weeks of treatment.Results Before the intervention there was no significant difference between the two groups in terms of any of the measurements.At the end of the 8 weeks of treatment all measurements in both groups had significantly improved compared with before training.The averages of all the measures were significantly better in the treatment group than in the control group.Conclusions Motor imagery training based on mirror neuron theory can improve the motor function and gait of stroke survivors.
7.Study of proton magnetic resonance spectroscopy of hippocampus in non - demented Parkinson's disease patients
Haidong HUANG ; Chunmin YANG ; Yan QU ; Kai ZHAO ; Jianwen GU ; Hui ZHANG
Clinical Medicine of China 2008;24(12):1185-1188
Objective To explore the clinical application value of proton magnetic resonance spectroscopy (1H-MRS) in the metabolism of the hippocampus in non-demented Parkinson's disease(PD) patients. Methods 1H-MRS localized to both hippocampus,was carried out in 36 non-demented PD (14 patients with Hoehn-Yahr stage Ⅰ,8 patients with Hoehn-Yahr stage Ⅱ,8 patients with Hoehn-Yahr stage Ⅲ ,and 6 patients with Hoehn-Yahr stage Ⅳ) and 20 age-matched healthy control subjects. The metabolite ratios of N-acetylasparatate (NAA)/creatine (Cr),and choline-containing compounds (Cho)/Cr in PD patients were compared with those in the age-matched healthy control subjects. Results NAA/Cr ratios were reduced significantly and Cho/Cr ratios were increased sig-nificantly in both hippocampus of patients with Hoehn-Yahr stage Ⅳ compared to those in the age-matched healthy control subjects (P<0.05). However,no significant differences in NAA/Cr and Cho/Cr ratios were found between patients with Hoehn-Yahr stage Ⅰ-Ⅲ and the age-matched healthy control subjects (P>0.05). Conclusion 1H-MRS can provide the metabolic information ,and reflect the pathological changes of nerve cell in the hippocampus of non-demented PD patients with Hoehn-Yahr stage Ⅳ. It is helpful to predict the risk of dementia in PD.
8.A novel intracranial Enterprise stent together with coils for the treatment of very small intracranial wide-necked aneurysms
Haidong HUANG ; Kai ZHAO ; Jianwen GU ; Yan QU ; Tao YANG ; Xun XIA ; Long LIN ; Hui ZHANG
Journal of Interventional Radiology 2010;19(2):91-94
Objective To make a preliminary investigation and summary of the technique and efficacy of the novel intracranial stent, Enterprise, together with hydro-detachable coils for the treatment of very small intracranial wide-necked aneurysms (diameter<3 nun and body-to-neck ratio<1.5). Methods Six cases with very small intracranial wide-necked aneurysms were treated with Enterprise stents and hydro-detachable coils. In 5 cases the Enterprise stent was implanted to cover the neck of the aneurysm, which was followed by the introduction of a microcatheter into the aneurysmal sac through the stent mesh to stuff hydro-detachable coils in order to fill the aneurysmal sac. In the remaining case, the microcatheter was placed into the aneurysmal sac before the Enterprise stent was inserted to embolize the aneurysm. Postoperative follow-up was conducted for 3-6 months. Results The operation was successfully completed in all 6 patients, with the implanted stents being in right place. The parent arteries remained patency in all patients. No complications occurred. Complete occlusion of aneurysmal cavity was obtained in four cases, and the occlusion degree of the aneurysmal cavity above 95% was seen in 2 cases. After the procedure, all the patients recovered well. Neither rebleeding nor symptoms related to thrombosis occurred during a clinic follow-up of 3-6 months. Conclusion Endovasculur embolization with Enterprise stent together with hydro-detachable coils is a safe and effective method for the treatment of very small intracranial wide-necked aneurysms. However, its long-term effect needs to be further observed.
9.Fasting plasma obestatin levels in patients with different glucose tolerance and its association with lipid metabolism
Pengying GU ; Dongmei KANG ; Yuan XIA ; Hui ZHENG ; Weidong WANG ; Jian ZHOU ; Cuiping ZHAO ; Yan CHEN
Chinese Journal of Geriatrics 2010;29(6):480-482
Objective To investigate whether fasting obestatin level is different in patients with impaired glucose tolerance or type 2 diabetes, and to explore the association between obestatin and lipid metabolism. Methods Eighty-four subjects without known diabetes were divided into three groups: normal glucose tolerance(NGT), impaired glucose tolerance (IGT) and type 2 diabetes (DM) Plasma obestatin levels were measured with a radioimmunoassay. The relationship between fasting obestatin levels and metabolic parameters was also analyzed. Results Fasting obestatin levels were lower in DM group [(2.82±0.78)ng/ml] and IGT group [(3.25±0.29)ng/ml] than in NGT group[(3.55±0.57) ng/ml, P<0.01]. Triglycerides and low density lipoprotein cholesterol levels gradually increased among the three groups (P<0.05). Multiple linear regression analysis revealed fasting obestatin level was independently associated with waist-to-hip ratio, triglyeride and low density lipoprotein cholesterol. The regression equation was obestatin=6.953-3.412×W/H-0.175×TG-0.123×LDL-C. Conclusions The decreased obestatin may be associated with IGR and T2DM, and obestatin level may be associated with lipid metabolism.
10.Association between nutrition and peripheral artery disease in continuous ambulatory peritoneal dialysis patients
Yue GU ; Chengguo HUANG ; Lei YAN ; Hui CHEN ; Bing LIU ; Fengmin SHAO
Chinese Journal of Nephrology 2014;30(8):580-585
Objective To investigate the association between nutrition and peripheral artery disease (PAD) in continuous ambulatory peritoneal dialysis (CAPD) patients.Methods One hundred and two stable CAPD patients from a single center were enrolled in this cross-sectional study.Automatic ankle-brachial index (ABI) measuring system was applied to examine ABI.Patients were divided into PAD group (ABI < 0.9) and non-PAD group (ABI≥0.9).Clinical data were collected.Biochemical parameters were detected.Nutritional status was evaluated by serum albumin,handgrip strength (HGS) and subjective global assessment (SGA).Logistic regression analysis was performed to estimate the association of PAD with each nutritional marker as well as other potential risk factors.Results The incidence of PAD was 23.53% (24/102).ABI was significantly lower in patients with malnutrition as compared to those without malnutrition [(0.72 ± 0.21) vs (1.04 ± 0.14),P<0.01].Compared with non-PAD patients,serum albumin (P < 0.01),HGS (P < 0.01),diastolic blood pressure (P < 0.05),serum creatine (P < 0.05)、blood urine nitrogen (P < 0.01) were significantly decreased,but age (P < 0.01),the incidence of malnutrition [SGA,P < 0.01],diabetic status (P < 0.01),cardiovascular disease history (P < 0.01) were significantly increased in PAD patients.Logistic regression analysis showed that serum albumin (OR=0.762,95% CI:0.611-0.948,P=0.015),HGS (OR=0.988,95% CI:0.979-0.997,P=0.013) were independent protective factors for PAD,malnutrition [(SGA),OR=21.101,95% CI:5.008-88.901,P<0.01] was independent risk factor for PAD in CAPD patients.Conclusions The PAD incidence of CAPD patients in our center is 23.53%.Nutrition is independent factor associated with PAD in CAPD patients.