1.Mechanism underlying mesenchymal stem cells to regulate autoimmune thrombosis of systemic lupus erythematosus
Chinese Journal of Tissue Engineering Research 2013;(45):7968-7974
BACKGROUND:Systemic lupus erythematosus is a complex autoimmune disease of unknown origin affecting virtual y every organ in the human body. It is characterized by abnormal activation of T, B lymphocytes. While aberrant T cells provide help to autoreactive B cells, the autoreactive B cells produce a variety of pathological autoantibodies and immune complex deposition, which could infiltrate the smal blood vessels directly or deposit in the vessel wal , thereby causing inflammatory necrosis of the vessel wal s. These changes wil narrow the vascular lumen, and promote thrombosis, leading to local tissue ischemia and dysfunction. Mesenchymal stem cells can regulate the immune disorders, play an anti-inflammatory role, and repair the immune thrombosis.
OBJECTIVE:To summarize the pathogenesis of immune thrombosis in systemic lupus erythematosus, as wel as to introduce the mechanism of mesenchymal stem celltherapy for immunity thrombosis.
METHODS:We searched the PubMed database, Springlink database, ScienceDirect database and HighWire database from January 1990 to June 2013 with the key words of“systemic lupus erythematosus, mesenchymal stem cell, thrombosis, T cells, B cells”in English. An online search of CNKI database, Wanfang database, VIP database from January 1990 to June 2013 was also conducted with the key words of“systemic lupus erythematosus, mesenchymal stem cell, thrombosis, T cells, B cells”in Chinese. A total of 267 literatures were screened out, and 48 documents were included in the review based on the inclusion and exclusion criteria.
RESULTS AND CONCLUSION:Mesenchymal stem cells are multipotential nonhematopoietic progenitor cells capable of multi-directional differentiating into various celltypes. Mesenchymal stem cells can suppress T-lymphocyte activation and proliferation, and inhibit secretion of interferon-γ, interleukin-4. Mesenchymal stem cells can also inhibit the proliferation of B cells and the secretion of pathogenic immunoglobulin IgM, IgG, IgA. Thus, mesenchymal stem cells can regulate immune homeostasis and reduce the deposition of autoantibodies and immune complexes, thereby protecting the blood vessels from injury, reducing the secretion of inflammatory cytokines, balancing the coagulation-anticoagulation, and decreasing thrombosis in systemic lupus erythematosus.
2.Role of NF-κB in the progression of aldosterone-induced renal injury and its associated mechanisms
Lei YANG ; Wei DING ; Minmin ZHANG ; Yong GU
Chinese Journal of Nephrology 2011;27(9):673-677
Objective To investigate the role of NF-κB in aldosterone-1%NaCl-induced renal injury in uninephrectimized SD rats and the potential mechanisms.Methods Thirty-teo male SD rats were uninephrectomized and treated for 4 weeks.Rats were divided into four groups randomly:control group (n=8),1%NaCl group (1%NaCl in chow,n=8),aldosterone group (1%NaCl in chow,0.75 μg/h aldosterone delayed relase by osmotic mini-pump,SC,n=8),PDTC group (1%NaCl in chow,0.75 μg/h aldosterone,SC,100 mg/kg PDTC,IG,n=8).Systolic blood pressure (SBP),urinary protein,renal function and renal morphologic were observed.The expression of intercellular cell adhesion molecule 1 (ICAM-1) and connective tissue growth factor (CTGF) were measured respectively by Western blotting and real-time PCR.The activity and location of NF-κB in renal cortex were detected by electrophoretic mobility shift assay (EMSA) and immunohistochemisty.Results Rats of aldosterone group exhibited higher blood pressure and more serious renal injury characterized by proteinuria,glomerular sclerosis compared with rats of the 1% NaCl group.Protein and mRNA levels of ICAM-1 and CTGF were significantly increased inaldosterone group rats than those in 1%NaCl group (all P<0.05).Moreover,all these changes were associated with an increase in NF-κB activity.Treatment with PDTC which is a specific inhibitor of NF-κB notably alleviated SBP,proteinuria and renal injury in aldosterone-infused rats.Furthermore,PDTC markedly reduced the expression of ICAM-1 and CTGF (all P<0.05).Conclusion PDTC can alleviate aldosterone-1%NaCl-induced renal injury in uninephrectimized SD rats by preventing the expression of ICAM-1 and CTGF.
3.A research of correlation between renal damage of patients with gestational diabetes mellitus and level of serum cystatin C
Xiantao QIU ; Yuanyuan QIU ; Yumei DAI ; Xiaoqiong GU ; Sujuan ZHANG ; Minmin CAI
International Journal of Laboratory Medicine 2014;(10):1289-1290
Objective To explore the correlation between renal damage of patients with gestational diabetes mellitus (GDM ) and level of serum cystatin C(Cys C) .Methods Eutocia puerperas with single birth in this center from January 2011 to December 2012 were retrospectively analyzed .400 puerperas ,who were confirmed as GDM by oral glucose tolerance test (OGTT) detection ,were collected .Among them ,200 puerperas with 24 h urinary protein content more than 0 .15 g during their 30 to 40 weeks of pregnancy were served as GDM group ,while another 200 puerperas with those not more than 0 .15 g as GDM control group .200 healthy puer-peras without GDM were served as the normal group .Serum uric acid ,creatinine ,urea ,Cys C and 24 h urinary protein content of them during their 30 to 40 weeks of pregnancy were detected .Results Serum uric acid and Cys C of patients in GDM group were obviously higher than those in the GDM control group(P<0 .05) ,while the differences of serum urea ,creatinine between the two groups showed no statistical significance (P>0 .05) .24 h urinary protein content was positively correlated with the serum uric acid and Cys C(r=0 .715 ,0 .863 ,P<0 .05) ,and had no correlation with urea and creatinine (P>0 .05) .Conclusion Serum Cys C may be used as indicators for early diagnosis and monitoring of renal damage in patients with GDM .
4.Expression of angiogenesis regulatory factors and their receptors in mouse kidneys with aging
Jie GUO ; Jing CHEN ; Minmin ZHANG ; Jianyong ZHONG ; Chuanming HAO ; Yong GU
Chinese Journal of Nephrology 2009;25(9):698-705
Objective To investigate the expression of vascular endothelial growth factor (VEGF), angiopoietin and their receptors (VEGFR and Tie2) in aging mice kidney and the possible roles in aging mice. Methods Mice were divided as follows: 4-month old group (n=6), 9-month old group (n=6), 12-month old group (n=6) and 20-month old group (n=6). Paraffin sections of the mice kidneys were stained by PAS. The density of glomerular microvascular was determined by renal perfusion with fluorescent dyes. The level of VEGF, VEGFR2 (Flk-1), Ang-1, Ang-2, Tie2 mRNA expression and protein abundance in kidney was determined by real-time PCR, immunochemistry, immunofluorescence and Western blot. Results Compared with other three groups, in the 20-manth old group, the glomerulosclerosis index (GSI) increased remarkbly (2.48±0.79 vs 0.53±0.19, 0.69±0.18, 1.50±0.70, P<0.05); the fluorescence intensity in glomeruli decreased (P<0.05). lmmunohistochemistry demonstrated that the TGF-131 level in the aging kidneys showed an increase trend in the glomerular tubulointerstitium, and especially in the glomeruli. Real-time PCR results revealed that compared with 4-month old group mice, the mRNA expression of VEGF, Flk-1, Ang-1, Ang-2, Tie2 of the other three groups decreased, the gene levels of VEGF, Flk-1, and Ang-2 fell about 90%, 50% and 80% (all P>0.05), and the gene levels of Ang-1 and Tie2 fell about 75% and 40% in 20-month-old group (all P<0.05). Western blot domonstrated that the protein abundace of VEGF, Flk-1, Ang-1, Ang-2, Tie2 also declined with aging, the protein level of VEGF, Flk-1, Ang-1, Ang-2 and Tie2 dropped by about 35%, 50%, 15%, 13% and 21% respectively in 20-month-old group as compared to 4-month-old group (all P<0.05). Expression of above 5 factors and glomerular fluorescence intensity were negatively correlated with Scr (P<0.05). Conclusions The mRNA expression and protein abundance of VEGF, Flk-1, Ang-1, Ang-2, Tie2 in mice kidneys decreases with aging. Angiogenesis regulatory factors may play important roles in aging progression of the mice kidney.
5.Comprehensive rehabilitation intervention for stroke patients with unilateral spatial neglect
Xudong GU ; Meihong ZHU ; Meifang SHI ; Jianmin FU ; Yunhai YAO ; Mei JIN ; Minmin JIN ; Meixia YANG
Chinese Journal of Physical Medicine and Rehabilitation 2009;31(3):177-180
Objective To observe the iffectiveness of comprehensive rehabilitationinterventions on stroke patients with unilateral spatial neglect (USN). Methods A total of 245 cases if strijd were examined to diagnose USN. Of the 245 patients,86 cases were diagnosed as being with USN, and divided into a control group(n=43 cases) and a treatment group (n=43 cases) randomly. The control group was treated with Bobath and Rood techniques in addition to routine clinical medical interventions, while the treatment group was treated with a comprehensive rehabilitation protocol for USN in addition to the same interventions for the control group. Both groups were assessed with regard to motor, balance function, walking performance, and USN severity as well as the activities of daily living (ADL) performance. Results After 8 weeks of treatment,both groups improved, but there showed a significantly statistical difference between the 2 groups in terms of Fugl-Meyer motor function scores (P<0.01), balance function scores (P<0.01) Holden walding function classifications (P<0.01), Barthel index(P<0.001) and USN severity scores(P<0.01). Conclusion Comprehensive USN rehabilitation intervention could improve motor, balance, walking functions and ADL performance and alleviate the USN severity in stroke patients with USN.
6.Down-regulation of nestin expression in the glomeruli with foot process effacement and its correlation with the degree of proteinuria
Li YOU ; Jing CHEN ; Wei SU ; Minmin ZHANG ; Weiyu ZHU ; Liyin ZHANG ; Chuanming HAO ; Yong GU
Chinese Journal of Nephrology 2008;24(6):405-410
Objective To investigate the expression of nestin, a type Ⅵ intermediate filament protein in the glomeruli with foot process effacement and the potential relationship between nestin expression in the kidney and the degree of proteinuria. Method Immunohistochemistry was used to determine the localization of nestin in the kidney samples obtained from needle biopsies of normal human and patients with minimal change disease (MCD). Puromycin aminonucleoside (PAN) nephrosis rat models were established by a single intraperitoneal injection of PAN. Both real time quatitative reverse PCR and Western blot methods were applied to evaluate the levels of nestin expression at day 1, 4, 10 and 20 after PAN injection. Results Immunohistochemistry showed that the expression of nestin in glomeruli of MCD patients was significantly reduced compared with normal samples (0.93±0.08 vs 1.65±0.12, P<0.05) . The mRNA and protein expressions of nestin in the rat kidney were transitorily increased by 1.23 folds and 1.48 folds of control group (NC) after 1 day of PAN injection (P<0.05), then decreased quickly in the following days. The mRNA levels of nestin in the kidney were 35.8% and 12.1% of NC after 4 days and 10 days of PAN injection, respectively, (P<0.01) as determined by real time PCR. After 20 days of PAN injury, nestin mRNA expression partly recovered to 65.8% of NC (P< 0.05 ). The protein levels of nestin detected by Western blot presented the similar trend, which were 77.0%, 58.0% and 83.4% of NC after 4 days, 10 days and 20 days of PAN injection, respectively (P<0.05). The degree of proteinuria in puromycin aminonucleoside nephrosis rats was negatively correlated with both mRNA and protein levels of nestin in the kidney(r=-0.667,P<0.05 and r=-0.621 ,P<0.05, respectively). Conclusions The expression of intermediate filament protein nestin is down-regnlated in the kidney characterized with foot process effacement and negatively correlated with the degree of proteinuria in puromycin aminonucleoside nephrosis rats. Nestin may play a potential role in modulating the structure and function of podocyte.
7.Association of the expressions of glomerular nephrin, vascular endothelial growth factor and its receptor with proteinuria in preeclampsia rats
Fang FANG ; Lin TAO ; Jianying NIU ; Guixiang CHEN ; Yunjiao ZHOU ; Jing CHEN ; Minmin ZHANG ; Yong GU
Chinese Journal of Nephrology 2010;26(6):460-465
Objective To investigate the association of the expressions of glomerular nephrin, vascular endothelial growth factor (VEGF) and its receptor (VEGFR) with proteinuria in preeclampsia rats. Methods A rat model of preeclampsia was developed by inhibitor of nitric oxide synthase (L-NAME). The systolic blood pressure (SBP) and 24 h urine protein were compared among the normal female group (n=6), the normal pregnant group (n=8), nonpregnant control group (n=6) and preeclampsia group(n=8). The kidney biopsies of each group were observed by light and electron microscopy. The glomerular nephrin was detected by Western blotting and real-time PCR. Immunofluorescence was used to detect the expression of WT1. The level of glomerular VEGF and VEGFR (Flt-1 and Flk-1) were evaluated by Western blotting. Results The level of glomerular nephrin protein in the rats with preeclampsia (0.0726±0.0074) was significantly lower compared with normal female group (0.3795±0.0509), normal pregnant group (0.2361±0.0437) and nonpregnant control group (0.7265±0.0503) (P<0.01, respectively), while the levels of nephrin mRNA were not significantly different among 4 groups. The expression of WT1 was not significantly different among 4 groups as well. The level of glomerular VEGF in preeclampsia group (1.5429±0.0898) was significantly higher compared with normal female group (1.1870±0.1160), normal pregnant group (1.3741 ±0.1165) and nonpregnant control group (1.0155±0.0742)(P<0.01,respectively). VEGFR (Flt-1 and Flk-1) was also significantly higher in preeclampsia rats compared with other control groups (P<0.05, respectively). Conclusions In preeclampsia rats, nephrin is decreased significantly and the glomerular VEGF-VEGFR is increased significantly compared with the other control groups. The abnormal expression of nephrin and VEGF-VEGFR may be involved in the preeclampsia proteinuria. The underlying mechanism of this phenomenon needs further research.
8.Relationship between multi-gene proteins in colorectal carcinoma complicat-ed with chronic schistosomiasis:an immunohistochemical study by using tis-sue microarray techniques
Daohua YANG ; Chengmin QIU ; Weiwei SUN ; Minmin GU ; Peifeng HE ; Yanyan XU
Chinese Journal of Schistosomiasis Control 2014;(4):405-409
Objective To investigate the relationship between p53,COX-2,Bax,c-myc genes and colorectal carcinoma complicated with chronic schistosomiasis. Methods One hundred and sixty patients with colorectal carcinoma were selected and divided into two groups;a schistosomiasis group(colorectal carcinoma complicated with chronic schistosomiasis,n=80)and a non-schistosomiasis group(colorectal carcinoma uncomplicated with chronic schistosomiasis,n=80). The tissue microarray tech-niques and immunohistochemistry method were used in all the patients to detect the expressions of p53,COX-2,Bax and c-myc proteins. Results The positive rate and level of p53 protein expression in the schistosomiasis group were lower than those in the non-schistosomiasis group,but there were no significant differences between the two groups(both P>0.05). The COX-2 protein in both groups was positive,but the positive expression level of COX-2 in the schistosomiasis group was higher than that in the non-schistosomiasis group,and there was a significant difference between the two groups(P<0.01). The positive rate and level of Bax protein expression were not significantly different between the two groups(both P>0.05). The positive rate of c-myc expression in the schistosomiasis group was higher than that in the non-schistosomiasis group,with a significant difference(P<0.01),but the positive expression level was lower than that in the non-schistosomiasis group,and there was a significant difference between the two groups(P<0.01). Conclusions Schistosome infection may impact on the deficiency of p53 of human colorectal cancer cells. It may promote the excessive expression of COX-2 protein,which is an indirect carcinogenic factor. The expression of Bax gene has no correlation with schistosome infection. The schistosome chronic infection may cause a persistent low level expression of c-myc gene.
9.Analysis of clinical characteristics and treatment effect of perianal Crohn's disease with or without proctitis
Ping ZHU ; Yugen CHEN ; Yunfei GU ; Minmin XU ; Hao WANG ; Hongjin CHEN ; Bolin YANG
Chinese Journal of Digestive Surgery 2016;15(12):1170-1175
Objective To investigate the clinical characteristics of perianal Crohn's disease (CD) with or without proctitis and compare the treatment effect of surgery combined with biological preparation.Methods The retrospective cohort study was conducted.The clinical data of 52 patients with perianal CD who were admitted to the Affiliated Hospital of Nanjing University of Traditional Chinese Medicine from June 2011 to October 2014 were collected.Thirty patients with inflammation involvement of the rectum and 22 patients without inflammation involvement of the rectum were respectively divided into the proctitis group and non-proctitis group.All the 52 patients underwent surgery combined with infliximab therapy.Observation indicators included:(1) clinical characteristics:gender,age,body mass index (BMI),lesion location,disease behavior,type of perianal lesions,history of perianal surgeries,CD activity index (CDAI),perianal disease activity index (PDAI),C-reactive protein (CRP),erythrocyte sedimentation rate (ESR),white blood cell (WBC),platelet (PLT) and albumin (Alb),(2) treatment and follow-up.Follow-up using outpatient examination was performed to evaluate the perianal lesions up to December 2015.Measurement data with normal distribution were described as-x ± s and comparison between groups was analyzed by the t test.Count data were described as the percentage,and comparison between groups was analyzed by the chi-square test and Fisher's exact probability.Results (1)Clinical characteristics:number of patients with BMI < 18.5 kg/m2 and with normal BMI were respectively 17,13 in the proctitis group and 6,16 in the non-proctitis group.Lesions located at ileum,colon and ileocolon were respectively detected in 3,9,18 patients in the proctitis group and 9,4,9 patients in the non-proctitis group.CDAI≥ 150 and < 150,CRP≥8 mg/L and < 8 mg/L,ESR > normal level and =normal level,Alb < 35 g/L and between 35 g/L and 50 g/L were respectively detected in 23,7,25,5,24,6,12,18 patients in the proctitis group and 8,14,8,14,8,14,2,20 in the non-proctitis group,with statistically significant differences between the 2 groups (x2 =4.446,6.855,8.563,12.076,10.211,6.163,P < 0.05).(2) Treatment and follow-up:all the 52 patients underwent more than 3 times infliximab therapies and perianal surgeries within 1 week after infliximab therapy.All the patients were followed up for a median time of 28 months (range,8-52 months).Thirty-four patients still underwent maintenance therapy of immunosuppressive agents and 18 didn't undergo maintenance therapy up to the end of follow-up.Twenty-two patients in the proctitis group and 12 patients in the non-proctitis group underwent maintenance therapy,with no statistically significant difference between the 2 groups (x2 =1.979,P > 0.05).The total healed rate,improvement rate and unhealed rate of perianal lesion were 55.8% (29/52),34.6% (18/52) and 9.6% (5/52),respectively.The number of patients with healed,improved and unhealed perianal lesions were 16,11,3 in the proctitis group and 13,7,2 in the non-proctitis group,respectively,showing no significant difference in treatment effects between the 2 groups (x2 =O.173,P > 0.05).Conclusions Patients with perianal CD combined with proctitis have higher activity of intestinal inflammation and worse nutritional status compared with patients without proctitis.However,there is no significant difference in the type and activity of perianal lesion between patients with or without proctitis.Surgery combined with biological preparation could render better clinical outcomes in treatment of perianal CD with proctitis.
10.NaF· EDTA-K2 negatively bias blood lipids and lipoproteins measurement in pregnant women
Yumei DAI ; Yaoxiang LONG ; Xiantao QIU ; Xiaoqiong GU ; Qihua LIANG ; Xiaojuan CHEN ; Minmin CAI
Chinese Journal of Laboratory Medicine 2014;(9):705-708
Objective To explore the impact of NaF · EDTA-K2 on blood lipids measurement in pregnant women , determine whetherthe empty-stomach plasma for OGTT could be used as substitute for serumin blood lipids analyses.Methods Fastingplasma with NaF · EDTA-K2 and serumfrom 100 pregnant women werecollected,andconcentration of CHO,TG, HDL,LDL,apoA1 and apoB were tested with Hitachi 7 600 automatic biochemical analyzer.Data were analyzed by SPSS 19.0 software.Results The concentrations oflipids and lipoproteins with NaF · EDTA-K2 were slightly lower than those of serum.There were statistical significances between the means of CHO , HDL, LDL, apoA1 and apoBof two groups ( P<0.05) except TG.Correlation coefficients of the six analyteswere CHO 0.968, TG 0.995, HDL 0.979, LDL 0.991, apoA1 0.692, apoB 0.846respectively.Standard Error of Estimate for plasma were: CHO 0.281, TG 0.094, HDL 0.077, LDL 0.112, apoA1 0.230, apoB 0.111 respectively.The modified coefficients were 1.08 for CHO, HDL and LDL, 1.14 for apoA1 and 1.07 for apoB.Conclusion NaF· EDTA-K2 negatively biased the blood lipidsmeasurement of CHO , HDL, LDL, apoA1 and apoB in pregnant women,yet lipids concentrations in plasma with NaF · EDTA-K2 were closely related to those in serum , which may be used to predict the bloodlipidslevel of pregnant women afterajusted.