1.Hypoxia-inducible factor-1alpha gene-modified umbilical cord blood mesenchymal stem cells transplantation in the treatment of spinal cord ischemia-reperfusion injury
Chinese Journal of Tissue Engineering Research 2015;(10):1592-1596
BACKGROUND:There are no available therapies for spinal cord ischemia-reperfusion injury, and stem cel transplantation is a focused topics. OBJECTIVE:To observe the therapeutic effect of hypoxia-inducible facotr-1α gene-modified umbilical cord blood mesenchymal stem cels (UC-MSCs) transplantedvia the infrarenal abdominal aorta on spinal cord ischemia-reperfusion injury in rats. METHODS:Thirty adult female Sprague-Dawley rats were randomly divided into three groups, with 10 rats in each group. The infrarenal abdominal aorta of rats was occluded surgicaly for 1 hour, and then the spinal cord reperfusion was restored. At 2 hours after reperfusion, 1 mL of 10% PBS, UC-MSCs suspension and hypoxia-inducible factor-1α-modified UC-MSCs suspension was injectedvia the infrarenal abdominal aorta, respectively, in the three groups. At 1, 6, 12 days after injection, Basso-Beattie-Bresnahan scores were recorded and western blot assay was used to detect hypoxia-inducible factor-1α protein expression in the spinal cord. The motor-evoked potential was determined at 12 days after injection. RESULTS AND CONCLUSION: Compared with the control group, the Basso-Beattie-Bresnahan scores were significantly higher (P < 0.05), the expression of hypoxia-inducible factor-1α protein in the spinal cord tissue was significantly increased (P < 0.05), the motor-evoked potential latency was shortened (P < 0.05) and the amplitude was increased (P< 0 .05) in the untransfected group and transfection group. Compared with the untransfected group, the Basso-Beattie-Bresnahan scores were significantly higher (P < 0.05), the expression of hypoxia-inducible factor-1α protein in the spinal cord tissue was significantly increased (P < 0.05), the motor-evoked potential latency was shortened (P < 0.05) and the amplitude was increased (P < 0 .05) in the transfection group. Above al, umbilical cord blood mesenchymal stem cel transplantation modified by hypoxia-inducible factor 1α has better effects on spinal cord ischemia-reperfusion injury.
2.The role of TSG-6 in inhibiting the secretion of IL-1β by bone-marrow-derived macrophages
zeng zeming ; fan ruihong ; nong qiyin
China Occupational Medicine 2022;49(2):148-152
Objective To investigate the role of tumor necrosis factor alpha stimulated gene/inducible protein 6(TSG-6)on
free silica(SiO2
)-induced secretion of pro-inflammatory cytokine interleukin(IL)-1β by bone-marrow-derived macrophages
(BMDMs). Methods i)BMDMs isolated from bone marrow were divided into eight groups:the control group was untreated;
lipopolysaccharide (LPS) group was stimulated by LPS with a concentration of 50 µg/L;The TSG-6 control group was
stimulated by 100 µg/L of recombinant mouse TSG-6. SiO2 model group was pre-stimulated with LPS for four hours,and then
stimulated with SiO2 suspension at a final concentration of 250 mg/L;Different dose of TSG-6 groups were firstly treated with
above concentrations of LPS and SiO2 suspension,then 10,20,50 and 100 µg/L of recombinant mouse TSG-6 were added
respectively;After 16 hours of culture,the cells were collected and the level of IL-1β in BMDMs supernatant was detected by
enzyme-linked immunosorbent assay(ELISA)to screen optimal concentration of TSG-6. ii)The cells of the control group,LPS
group,SiO2 model group,TSG-6 optimal concentration group and TSG-6 control group were collected. The expression of IL-1β
and components of its related pathways in BMDMs was detected by Western blot,including IL-1β,pro-IL-1β,caspase-1,pro
dcaspase-1,asc type amino acid transport and NOD-like receptor protein 3(NLRP3). Results i)Compared with the control
group,the expression of IL-1β in SiO2 model group was increased significantly(P<0.01). Compared with SiO2 model group,the
expression of IL-1β in 20,50,100 µg/L dose of TSG-6 groups were decreased significantly(all P<0.01),and the optimal
concentration of TSG-6 was found to be 100 µg/L. ii)Compared with the control group and LPS group,the relative expression
levels of IL-1β,caspase-1 and NLRP3 in SiO2 model group were increased significantly (all P<0.05). Compared with
SiO2 model group,the expression levels of IL-1β、caspase-1 and NLRP3 were decreased in 100 µg/L TSG-6 group(all P<0.05).
Conclusion TSG-6 could inhibit BMDMs to secret pro-inflammatory cytokine IL-1β by down-regulating the expression of
NLRP3 and caspase-1.
3.The stimulate angiogenesis effect of Shexiangbaosin Pills on the hearts of myocardial infarction rats
Shanshan WANG ; Yong LI ; Weihu FAN ; Ruihong DAI ;
Chinese Traditional Patent Medicine 1992;0(06):-
Objective:The stimulate angiogenes effect and mechanism of Shexiangbaoxin Pills on coronary collateral development in the hearts of experimental myocardial infarction rats were studied. Methods:24 myocardial infarction rats were randomly divided into 3 groups, 8 rats in group A were treated with Shexiangbaoxin Pills, 8 rats in group B were treated with Beifuji and heparin, and 8 rats in group C were treated with 0.9% normal saline as control. Infarct area, the contents of VEGF、bFGF and VⅢ factor, and vascular density in the edge of infarct section were measured after 6 weeks treating.Results: Infarct area in group A was obviously less than that in group C, the contents of VEGF、bFGF and VⅢ factor in the edge of infarct section and vascular density in group were significantly increased compared with those in group C. Conclusions: Shexiangbaoxin Pills could stimulate angiogenesis of the collateral branch of coronary artery in ischemic myocardium of rats and showed good protective on myocardial ischemia.
4.The roles of ubiquitin-proteasome inhibitor in atherosclerosis
Haimei FAN ; Yuee SHEN ; Kun LI ; Ruihong SUN
International Journal of Cerebrovascular Diseases 2012;20(5):389-393
Atherosclerosis (AS) is a common underlying disease that hazard to human health.It is closely associated with stroke,hypertension,coronary artery disease,and diabetes.AS on the premise of vascular intimnal injury,excessive smooth muscle cell proliferation,inflammatory cell infiltration,oxidative stress,apoptosis and other mschanisms participate together.In eucaryotic organisms,most proteins are degraded by ubiquitin-proteasome system (UPS).An increasing number of evidence indicates that UPS is associated with the occurrenee and development of AS and complications.This article reviews the relationship between.UPS and AS,as well as the effect of ubiquitin-proteasome inhibitor on AS.
5.Experimental Study on Effect of Shexiangbaoxin Pills on Morphosis and Function of Left Ventricle after Myocardial Infarction in Rat
Xinping LUO ; Haiming SHI ; Zhiyu ZENG ; Weihu FAN ; Shouyi WANG ; Ruihong DAI ;
Chinese Traditional Patent Medicine 1992;0(07):-
Objective: To investigate the effect of Shexiangbaoxin Pills on morphosis and function of left ventricle after myocardial infarction in rat. Methods: The rat myocardial infarction models induced by ligaturing coronary artery were randomly divided into the myocardial infarction control group, Shexiangbaoxin Pill group and captopril group. The hemodynamic parameters and cardiac functions in 2 or 6 weeks after treatment were determined. Meantime, the morphological parameters of left ventrile (left cardiac chamber size, attenuation proportion of ventricular wall of infarction area, and expansion index of left ventrile), were studied. Results: Shexiangbaoxin Pills could reduce the distention of left ventrile and expansion of infarction area of rat in 6 weeks after infarction. It could obviously improve the contraction function of left ventrile after myocardial infarction. Conclusion: Shexiangbaoxin Pills can improve left ventricular reconstitution after myocardial infarction.
6.The role of endothelial microparticles in Beh(c)et's disease
qiuyu FAN ; Ke XU ; Liyun ZHANG ; Gailian ZHANG ; Dan MA ; Yin LIU ; Pengyan QIAO ; Juan LI ; Ruihong HOU
Chinese Journal of Rheumatology 2017;21(12):824-828,后插1
Objective Endothelial microparticles (EMPs) are direct indicator of endothelial cell activation or apoptosis,and may also reflect endothelial inflammation,increased coagulation,and vascular tone.The aim of this study is to investigate whether EMPs would be able to evaluate systemic involvement and be a new indicator of disease activity in Beh(c)et's disease (BD).Methods Thirty-nine consecutive BD patients (who fulfilled the modified International Study Group on BD in 1990 or International Criteria for BD in 2006) and 67 age and sex-matched healthy controls were enrolled (Including 37 patients with hypertension and 30 healthy subjects).The plasma levels of EMPs were measured by flow cytometry utilizing specific labels for endothelial MPs (CD31+ and CD42b-).The measurement data of each group were expressed as-x±s,and the comparison data betwen groups were analyzed by independent sample t test and analysis of variance,Spearman/Pearson correlation analysis,P<0.05 was statistically significant.Results The levels of circulating EMPs (CD31 + and CI42b-) were significantly elevated in the case group compared with the healthy control group and hypertension (F=6.845,P<0.05).Moreover,BD patients plasma EMPs were positively correlated with active BD (r=0.802,P<0.05).Vascular involvement in BD patients was higher than in patients without vascular EMPs,t=4.707,P<0.05.Gastrointestinal involvement in BD patients was more frequent than that in patients without Gastrointestinal involvement,t=2.673,P<0.05.Conclusion Levels of circulating EMPs are elevatedd in BD patients and correlated with disease activity in BD.Elevated EMPs may be a potential indicator to predict disease activity of BD.The plasma level of EMPs is increased,which indicats increased risk of vascular and digestive tract involvement in BD.
7.An investigation on surgical-site infection among post cesarean section patients with Burkholderia cepacia contaminated ultrasonic couplant
Man WANG ; Lijie ZHANG ; Shenglin XIA ; Haidong WU ; Ruihong ZHANG ; Mugeng FAN ; Tao WANG
Chinese Journal of Epidemiology 2014;(5):566-568
Objective In May 2013,an abnormal increase of surgical-site infection among post cesarean section patients was reported at one hospital in Zhongshan. An investigation was conducted to identify the risk factors and related control measures. Methods All the reported surgical-site infection records among post cesarean section patients were checked. A review of cesarean section schedules of health workers was also performed. An 1∶2 case-control study was conducted among surgical-site infection cases in May 2013. Microbiologic cultures were performed on 2 surgical site secretion samples and 12 samples from the environment. All the positive isolates were molecular typed by pulsed field gel electrophoresis(PFGE). Results In May 2013,4 post cesarean section patients who developed surgical-site infection symptom at one hospital in Zhongshan were reported,with an attack rate as 10.3%(4/39). The emergence time of symptom was 2-3 days after operation. All of the 4 cases underwent an emergency operation. The median time interval for cases from admission to operation was 7.2 hours(ranged from 2 to 9 hours),lower than that seen in the controls,with a median time of 20.8 hours (Z=5.50,P=0.03). Two of the 4 cases took type-B ultrasonic inspection 1.4 h and 8.4 h before the operation,and the other two cases took continuous fetal heart monitoring 2 hours before the operation. Skin of the operation area on the 4 cases had been exposed to ultrasonic couplant,without a thorough clean. The proportion of type-B ultrasonic inspection or continuous fetal heart monitoring was much higher in cases than in controls(χ2=5.19, P=0.01). Burkholderia cepacia (BC) isolates were discovered from:one surgical site secretion,2 type-B ultrasonic probe samples,one ultrasonic couplant in use and one ultrasonic couplant unopened. All the isolates were identified as 100%identical by PFGE. Conclusion The skin of operation area of cesarean section patients had been exposed to BC contaminated ultrasonic couplant without thorough cleaning,which seemed to be related to the outbreak of surgical-site infection,in our case.
8.An investigation on surgical-site infection among post cesarean section patients with Burkholderia cepacia contaminated ultrasonic couplant.
Man WANG ; Lijie ZHANG ; Shenglin XIA ; Haidong WU ; Ruihong ZHANG ; Mugeng FAN ; Tao WANG
Chinese Journal of Epidemiology 2014;35(5):566-568
OBJECTIVEIn May 2013, an abnormal increase of surgical-site infection among post cesarean section patients was reported at one hospital in Zhongshan. An investigation was conducted to identify the risk factors and related control measures.
METHODSAll the reported surgical-site infection records among post cesarean section patients were checked. A review of cesarean section schedules of health workers was also performed. An 1 : 2 case-control study was conducted among surgical-site infection cases in May 2013. Microbiologic cultures were performed on 2 surgical site secretion samples and 12 samples from the environment. All the positive isolates were molecular typed by pulsed field gel electrophoresis (PFGE).
RESULTSIn May 2013, 4 post cesarean section patients who developed surgical-site infection symptom at one hospital in Zhongshan were reported, with an attack rate as 10.3% (4/39). The emergence time of symptom was 2-3 days after operation. All of the 4 cases underwent an emergency operation. The median time interval for cases from admission to operation was 7.2 hours (ranged from 2 to 9 hours), lower than that seen in the controls, with a median time of 20.8 hours (Z = 5.50, P = 0.03). Two of the 4 cases took type-B ultrasonic inspection 1.4 h and 8.4 h before the operation, and the other two cases took continuous fetal heart monitoring 2 hours before the operation. Skin of the operation area on the 4 cases had been exposed to ultrasonic couplant, without a thorough clean. The proportion of type-B ultrasonic inspection or continuous fetal heart monitoring was much higher in cases than in controls (χ² = 5.19, P = 0.01). Burkholderia cepacia (BC) isolates were discovered from:one surgical site secretion, 2 type-B ultrasonic probe samples, one ultrasonic couplant in use and one ultrasonic couplant unopened. All the isolates were identified as 100% identical by PFGE.
CONCLUSIONThe skin of operation area of cesarean section patients had been exposed to BC contaminated ultrasonic couplant without thorough cleaning, which seemed to be related to the outbreak of surgical-site infection, in our case.
Adolescent ; Adult ; Burkholderia cepacia ; Case-Control Studies ; Cesarean Section ; Cross Infection ; etiology ; Equipment Contamination ; Female ; Humans ; Pregnancy ; Surgical Wound Infection ; etiology ; Young Adult
9.An ultrapotent pan-β-coronavirus lineage B (β-CoV-B) neutralizing antibody locks the receptor-binding domain in closed conformation by targeting its conserved epitope.
Zezhong LIU ; Wei XU ; Zhenguo CHEN ; Wangjun FU ; Wuqiang ZHAN ; Yidan GAO ; Jie ZHOU ; Yunjiao ZHOU ; Jianbo WU ; Qian WANG ; Xiang ZHANG ; Aihua HAO ; Wei WU ; Qianqian ZHANG ; Yaming LI ; Kaiyue FAN ; Ruihong CHEN ; Qiaochu JIANG ; Christian T MAYER ; Till SCHOOFS ; Youhua XIE ; Shibo JIANG ; Yumei WEN ; Zhenghong YUAN ; Kang WANG ; Lu LU ; Lei SUN ; Qiao WANG
Protein & Cell 2022;13(9):655-675
New threats posed by the emerging circulating variants of SARS-CoV-2 highlight the need to find conserved neutralizing epitopes for therapeutic antibodies and efficient vaccine design. Here, we identified a receptor-binding domain (RBD)-binding antibody, XG014, which potently neutralizes β-coronavirus lineage B (β-CoV-B), including SARS-CoV-2, its circulating variants, SARS-CoV and bat SARSr-CoV WIV1. Interestingly, antibody family members competing with XG014 binding show reduced levels of cross-reactivity and induce antibody-dependent SARS-CoV-2 spike (S) protein-mediated cell-cell fusion, suggesting a unique mode of recognition by XG014. Structural analyses reveal that XG014 recognizes a conserved epitope outside the ACE2 binding site and completely locks RBD in the non-functional "down" conformation, while its family member XG005 directly competes with ACE2 binding and position the RBD "up". Single administration of XG014 is effective in protection against and therapy of SARS-CoV-2 infection in vivo. Our findings suggest the potential to develop XG014 as pan-β-CoV-B therapeutics and the importance of the XG014 conserved antigenic epitope for designing broadly protective vaccines against β-CoV-B and newly emerging SARS-CoV-2 variants of concern.
Angiotensin-Converting Enzyme 2
;
Antibodies, Neutralizing
;
Antibodies, Viral
;
COVID-19
;
Epitopes
;
Humans
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SARS-CoV-2/genetics*
;
Spike Glycoprotein, Coronavirus/genetics*