1.Therapeutic effect of umbilical cord-derived mesenchymal stem cell transplantation in systemic lupus erythematosus patients with different patterns of syndromes
Yu TANG ; Ruixia LIU ; Yingying QIU ; Jinbing RUI ; Jing LI
Chinese Journal of Tissue Engineering Research 2015;(45):7298-7303
BACKGROUND:Systemic lupus erythematosus (SLE) is classified into four types, and the major treatment is to tonify kidney and nourishyin, clear blood stasis and toxin by the traditional Chinese medicine (TCM). Even though, there are stil many patients with poor efficacy. Mesenchymal stem cels have the capacity of multiple differentiation, hematopoietic support and immune regulation, thus having been used for the treatment of refractory, recurrent SLE and achieving good effects. OBJECTIVE:To investigate the therapeutic effect of umbilical cord-derived mesenchymal stem cel transplantation on SLE patients with different patterns of syndromes. METHODS: Twenty-one SLE patients were clustered to four syndrome types of TCM, including heat-toxin,yin deficiency of liver and kidney,yang deficiency of spleen and kidney, andqi stagnation and blood stasis. The changes in clinical and laboratory indicators were analyzed statisticaly before and after cel transplantation. RESULTS AND CONCLUSION:The level of 24-hour proteinuria and SLE disease activity index scores in SLE patients were significantly decreased at 1, 3, 6 months after cel transplantation (P < 0.01). Umbilical cord-derived mesenchymal stem cel transplantation could significantly reduce the 24-hour proteinuria in SLE patients withyin deficiency of liver and kidney at 1, 3 and 6 months (P < 0.01), while slightly reduce the 24-hour proteinuria in SLE patients with heat-toxin andqi stagnation and blood stasis at 1, 3 months (P < 0.05) as wel as in SLE patients withyang deficiency of spleen and kidney at 1 month (P < 0.05). Additionaly, umbilical cord-derived mesenchymal stem cel transplantation could increase the serum albumin levels in al the SLE patients (P < 0.01), although the changes in patients with heat-toxin were moderate (P < 0.05). Al the SLE patients of four types had an increasing trend of their platelet counting after cel transplantation, but there was no statistical difference before and after cel transplantation. Taken together, umbilical cord-derived mesenchymal stem cel transplantation is effective for treatment of SLE, but has different therapeutic efficacy on SLE patients with different syndrome types of TCM.
2.Endoplasmic reticulum stress-mediated high-fat diet, palmitic acid-induced insulin resistance in skeletal muscle and interventional effects of fenofibrate
Yingying BAO ; Yunxia LU ; Guanjun CHEN ; Jingjing CHENG ; Qiu ZHANG
Chinese Pharmacological Bulletin 2014;(11):1557-1563
Aim To investigate endoplasmic reticulum stress ( ERS)-mediated high-fat diet and palmitic acid-induced insulin resistance ( IR) in skeletal muscle and interventional effects of fenofibrate both in vivo and in vitro tests. Methods Female SD rats were randomly subjected to a standard control diet ( SCD) or high-fat diet ( HFD) for 20 weeks, then the HFD group was di-vided into high-fat-diet group and high-fat-diet group treated with fenofibrate ( HFD +FF, 30 mg · kg-1 · d-1 ) for another 8 weeks. The changes of IR and ex-pression of peroxisome proliferator-activated receptor α( PPARα) , glucose regulated protein 78 ( GRP78 ) and transcription factors GADD153 ( CHOP ) were as-sessed respectively. C2C12 myotubes were divided into normal control group ( NC ) , model group ( palmitic acid, PA) , postive control drug group ( tunicamycin, TM) and treatment group ( fenofibric acid, FA+PA) , the expressions of GRP78 and CHOP were assessed re-spectively. Insulin-stimulated phosphorylation of Akt was also analyzed to detect changes of insulin sensitivi-ty in C2 C12 . Results The high-fat diet induced obvi-ous IR and upregulated ERS markers GRP78 and CHOP in skeletal muscle of rats, and these responses were attenuated by treatment with fenofibrate. Incuba-tion of myotubes with palmitic acid or tunicamycin sig-nificantly increased expression of ERS markers GRP78 and CHOP. Meanwhile, insulin-stimulated phosphoryl-ation of Akt was inhibited obviously. Pre-incubation with FA markedly inverted PA-induced ERS and insu-lin-stimulated phosphorylation of Akt. Conclusion Fenofibrate ( fenofibric acid) has obvious effects of IR on skeletal muscle tissues and cells, which may be re-lated with reduced expression of GRP78 and CHOP in ERS.
3.Effects of PKC activation on expression of Nrf2 in rabbit RPE cells
Dong WEI ; Yingying JIAO ; Lulu QIU ; Zhaoyi SUN
Recent Advances in Ophthalmology 2017;37(5):419-422
Objective To investigate whether activation of protein kmase C (PKC) can induce the activation and nuclear translocation of nuclear factor enthroid 2-related factor 2 (Nrf2) in retinal pigment epithelial (RPE) cells in vitro,and explore whether PKC activation may affect the expression of Nrf2 in RPE cells.Methods PKC-specific activator phorbol ester PMA was used to culture rabbit RPE cells and RPE cells pretreated with Nrf2 inhibitor for 24 hours.Immunofluorescence and Western blot were used to detect Nrf2 in the nucleus of the expression of the situation,the data were obtained for statistical analysis.Results The expression of Nrf2 protein in the nucleus of PRE cells was detected by immunofluorescence.Compared with the control group,the expression of Nrf2 protein in the nucleus of RPE cells increased in the experimental group,and the increase of PMA + Nrf2 inhibitor group was lower than that of PMA group.The difference between the two groups was statistically significant (P <0.05).Western blot analysis showed that the Nrf2 protein in the nucleus of PRE was quantitatively analyzed by image analysis.The gray value of the control group was significantly different (0.286 ± 0.013 in the control group,1.304 ± 0.033 in the PMA group and 0.671 ± 0.087 in the PMA + Nrf2 inhibitor group,P < 0.05).Conclusion PKC can activate nuclear translocation of Nrf2 in rabbit RPE cytoplasm,and Nrf2 inhibitor can attenuate the effect of PKC.
4.Relationship between Motor Function and Balance for Spastic Hemiplegia after Stroke
Yixiong CHEN ; Yingying NI ; Weijian CHEN ; Yun ZHANG ; Chengyao QIU ; Yunyi LIU ; Zhongrui FENG ; Xing CHEN
Chinese Journal of Rehabilitation Theory and Practice 2010;16(6):576-578
ObjectiveTo discuss the relationships among spastic paralysis and motor function, balance function and other clinical variables after stroke.MethodsAssessed the clinical spastic index of hemiplegic lower limbs with CSI scale, motor function with Fugl-Meyer Assessment, and balance function with Berg Equilibrium Scale, respectively. And then analyzed the relationship between clinical spasm index with motor function, balance function of the hemiplegic lower limbs with Pearson correlation analysis. Finally, ascertained which was the most important factor affecting the clinical spasm index of spastic lower limbs with stepwise regression analysis.ResultsThere is negative correlation between clinical spasm index with motor function and balance function, respectively. Tendon reflex, muscular tension and clonus are the deciding factors to motor function(P<0.05) and balance function(P<0.05) of the hemiplegic lower limbs.ConclusionThe clinical spasm index of hemiplegic limbs can affect the recovery of motor function and balance function significantly. So, assessing and improving the clinical spasm index of paralytic lower limbs can optimize the rehabilitation program to stroke patients.
5.Effect of Electroencephalograph Bionic Electrical Stimulation on Persistent Vegetative State: Cerebral Blood Flow and Metabolism
Yingying NI ; Lixia DENG ; Chengyao QIU ; Wensheng WANG ; Mengliang MA ; Yunyi LIU
Chinese Journal of Rehabilitation Theory and Practice 2015;21(3):303-306
Objective To study the effect of electroencephalograph (EEG) bionic electrical stimulation at Wangu (GB12), Tianzhu (BL10), Neiguan (PC6) on cerebral blood flow and metabolism in patients with persistent vegetative state (PVS). Methods 60 patients with PVS were divided into observation group (n=30) and control group (n=30) according to the random number table. The control group received routine treatment, including basic management, hyperbaric oxygen therapy, awaking medicine, sensory stimulation, and so on; while the observation group received EEG bionic electrical stimulation at bilateral Tianzhu, Wangu (cheif electrodes) and Neiguan (auxiliary electrodes) in addition. They were treated for 30 days. They were assessed with the PVS score, and observed with transcranial Doppler ultrasound (TCD) and magnetic resonance spectroscopy (MRS) one day before and one day after treatment. Results The incidence of improvement was 86.67% in the observation group, more than 60.00% in the control group (P<0.05). The difference of blood flow velocity before and after treatment (ΔVm) of anterior-middle cerebral artery was more in the observation group than in the control group respectively (P< 0.001), as well as those of posterior cerebral-vertebral-basilar artery (P<0.01). The N-acetyl aspartic acid/creatine (NAA/Cr) increased more in the observation group than in the control group respectively (P<0.01), and the choline/creatine (Cho/Cr) decreased more (P<0.01), after treatment. Conclusion EEG bionic electrical stimulation can improve the cerebral circulation and metabolism in patients with PVS, which may associate with the wake promoting.
6.Mild hypothermia protects cerebral ischemia-reperfusion injury in rats by downregulating inhibitor of differentiation 2
Li REN ; Jin XING ; Zilong WEI ; Zhihan WANG ; Liang ZHAO ; Yongming QIU ; Yingying LIN
International Journal of Cerebrovascular Diseases 2017;25(3):223-227
Objective To investigate the protective effect of mild hypothermia on cerebral ischemia-reperfusion injury in rats and the effect of mild hypothermia on the expression of inhibitor of differentiation 2 (Id2) protein.Methods A total of 72 adult male rats were randomly divided into a sham operation group,a normothermia group,and a mild hypothermia group.A model of middle cerebral artery occlusion was induced by a suture method.The mild hypothermia group was treated with low temperature (anal temperature 33±1 ℃,tympanic membrane temperature 31±1 ℃).Modified Neurological Severity Score (mNSS) was used to evaluate neurological deficits,triphenyltetrazolium chloride staining was used to detect infarct volume,and Western blot was used to detect the Id2 expression in the ischemic cortex at ischemia-reperfusion 6,12,24,and 72 h,respectively.ResultsThe mNSS scores in the mild hypothermia group were significantly lower than those in the normothermia group,the infarct volumes were significantly smaller than those in the normothermia group at ischemia-reperfusion 6,12,24,and 72 h (all P<0.001).Western blot analysis showed that the Id2 expressions in the ischemic cortex in the mild hypothermia group were significantly lower than those in the normothermia group at ischemia-reperfusion 6,12,24,and 72 h (all P<0.05).Conclusion s Mild hypothermia can decrease neurological deficits and reduce infarct volume after cerebral ischemia-reperfusion,its mechanism may be associated with the down-regulation of the Id2 expression.
7.A preliminary study of the correlation between the percentage of follicular helper T cells in peripheral blood and systemic lupus erythematosus disease
Haiyan YOU ; Hong MA ; Zhijun JIAO ; Yingying QIU ; Ling WU ; Bei WANG ; Xiaoyue ZOU
Chinese Journal of Rheumatology 2013;(6):396-399
Objective To investigate the change and significance of T follicular helper cells(Tfh) in the peripheral blood of patients with systemic lupus erythematosus (SLE).Methods The percentage of CD4+ CXCR5+ICOS+ Tfh cells and the expression of activation marker CD69 on the Tfh cells of peripheral blood from 60 SLE patients (30 in active and 30 in inactive) and 30 healthy subjects (control group) were determined by flow cytometry.The correlations between the percentage of Tfh cells of SLE patients and SLE disease activity index (SLEDAI),anti-nuclear antibody (ANA) titers and the levels of complement 3 (C3),complement 4 (C4) were analyzed.ANOVA and Pearson's correlation analysis were used for statistical analysis.Results The percentage of the Tfh cells in the peripheral blood of active SLE patients was higher than inactive patients and healthy controls [(0.80±0.17)% vs (0.63±0.13)% vs (0.57±0.08)%; P<0.01],there was also statistical significance between inactive patients and healthy controls (P<0.05).The expression of CD69 on the Tfh cells in the peripheral blood of active SLE patients was higher than that in inactive and healthy controls [(7.3±1.6)% vs (5.9±1.3)% vs (5.2±0.9)%; P<0.01].There was no statistical significant difference between inactive patients and healthy controls (P>0.05).The percentage of Tfh cells of SLE patients was significantly related with SLEDAI (r=0.680,P<0.01) and C3 levels (r=-0.416,P<0.05),butthere was no correlation between that and the ANA titer,C4 levels (r=-0.042,-0.204,P>0.05).Conclusion Increased percentage and activity of the Tfh cells in the peripheral blood of patients might contribute to the pathogenesis and development of SLE.
8.The profile of Th17/Treg balance in the peripheral blood of patients with systemic lupus erythematosus
Haiyan YOU ; Jing LI ; Zhijun JIAO ; Yi WANG ; Yingying QIU ; Ling WU ; Donghai ZHENG
Chinese Journal of Rheumatology 2012;16(1):50-52
ObjectiveTo investigate the profile of Th17/Treg balance in the peripheral blood of patients with systemic lupus erythematosus (SLE).MethodsThirty-two SLE patients in active disease were selected and 30 SLE patients in remission were included in this study.The control group was consisted of 25healthy individuals.The expressions of IL-17 and FoxP3 on CD4+ T cells in the peripheral blood were assessed by flow cytometry and the mRNA levels of these two cytokines were examined by quantitative PCR respectively.ANOVA was used for statistical analysis.ResultsThe percentage of CD4+IL-17+ T cells and IL-17mRNA expression of the active group were significantly higher than those of the remission group and control group[(l.0l±0.22)%,(2.04±0.63)vs (0.48±0.16)%,(1.12±0.34) vs (0.41±0.12)%,1; P<0.01].There was no difference between the remission group and control group(P>0.05).However,the percentage of CI4+FoxP3 + T cells and FoxP3 mRNA expression of the active group were significantly lower than those of the remission group and control group [(2.36±t0.54)%,(0.42±0.16) vs (4.34±0.95)%,(0.87±t0.28) vs (5.09±11.17)%,1; P<0.01 ],and there was also significant differencesbetween the remission group and control group(P<0.05).ConclusionThl7/Treg balance shift may exist in the peripheral blood of patients with SLE and the degree of imbalance may be related to disease activity of SLE.
9.Effect of berberine on the expression of nephrin, podocin and intergrin α3β1 in diabetic nephropathy rats
Haihua DING ; Yuanye QIU ; Yingying WANG ; Weijian NI ; Liqin TANG ; Wei WEI
Chinese Pharmacological Bulletin 2015;(10):1414-1420
Aim To investigate the effect of berberine on the expression of nephrin, podocin and intergrinα3β1 in diabetic nephropathy ( DN ) rat model, and further probe in to the renoprotective effects of berber-ine and its potential mechanisms. Methods The rat model of DN was induced by intraperitoneal injection of streptozotocin ( STZ ) after fed with high-sugar and high-fat diet for six weeks. The rats were assigned into 6 groups randomly: normal control group, DN model group, BBR (50,100 and 200 mg·kg-1 ) treatment group and enalaprilat positive control group ( 1 mg · kg-1 ) . The distribution and expression of kidney podocyte related proteins nephrin, podocin and interg-rinα3β1 were detected by immunohistochemical meth-od following electron microscopy observation ( × 1000 ) and high magnification observation( × 400) and West-ern blot. Results The podocyte related protein neph-rin, podocin and intergrin α3β1 were mainly distribu-ted in podocyte, but slightly different. Compared with normal control group, the expresion of podocyte related protein nephrin, podocin and intergrin α3β1 was de-creased obviously; compared with model group, BBR (100 and 200 mg·kg-1 ) treatment group could sig-nificantly suppress the abnormalities of pathological changes of the kidney and upregulate the expression levels of podocyte specific protein nephrin, podocin and intergrin α3β1 in the kidney of diabetic rats with nephropathy. Conclusions Berberine could alleviate the abnormalities of kidney pathological changes and proteinuria production in the DN model rats, which may be related to the upregulation of the expression of the podocyte proteins nephrin, podocin and intergrinα3β1.
10.CT Features of Bone Flare Phenomena of Metastatic Bone Disease in Lung Cancer
Yanfang QIU ; Zhi WEN ; Xiaoyan XU ; Yongli WANG ; Yingying YU ; Yanping ZHAO
Chinese Journal of Medical Imaging 2015;(12):929-933
PurposeThe bone flare phenomena has been well described on bone scintigraphy for efficacy monitoring up to now, but our knowledge has been rarely described on MSCT, the phenomena may be erroneously classiifed as disease progression. This article intends to evaluate the existence and CT features of bone flare phenomena of metastatic bone disease in lung cancer patients treated with ibandronate, to raise awareness of this phenomenon.Materials and Methods The clinical and image data of 45 patients with bone metastases of lung cancer were retrospectively analyzed prior to treatment and 3, 6 months after treatment, the change of CT value and CT features 3 months after treatment between bone flare phenomena group, progressive disease group 1 and progressive disease group 2 were compared.Results The incidence of bone flare phenomena was 6.7% (3/45). 3 months after treatment, CT value of the bone flare phenomena group and progressive disease group 1 changed when compared with before treatment, the differences were statistically signiifcant (t=-5.787 and-2.788,P<0.05) and there was no statistically signiifcant difference (t=1.691,P>0.05) of CT value in the progressive disease group 2 after 3 months' treatment. After 3 months' treatment, the bone flare phenomena group mostly appeared as osteogenic sclerosis of osteolytic lesions, while the cases of progressive disease group mostly appeared as new periosteal reaction of the lesion, or osteogenic/mixed lesion combined with osteolytic damages, the difference between the two groups was statistically signiifcant (χ2=10.139, 8.041 and 4.154,P<0.01,P<0.05). There was no statistically signiifcant difference in increase of density in osteosclerotic lesions (χ2=0.059, P>0.05).Conclusion In patients treated with ibandronate, when there is therapeutic effect evaluation standard of bone metastases (disease progression) and clinical comprehensive curative effect evaluation standard (effective) discordance at 3 months after treatment, it can be interpreted as bone flare phenomena, and the change of CT features contributes to the differential diagnosis of bone flare phenomena with progressive disease.