1.The protective effect of Nrf2/ARE pathway on islet B cell in type 2 diabetic rats
Chinese Journal of Endocrine Surgery 2016;10(3):201-205
Objective To investigate the effects of Nrf2/ARE pathway activator upregulating the expression of phase Ⅱ detoxifcation enzymes and antioxidant enzymes in islet B cell on its morphological structure in type 2 diabetic rats.Methods Type 2 diabetic rats were divided into diabetes model group (DM group),and tertiary-Butylhydroquinone intervention group(tBHQ group).At the same time,the normal control group (NC group)was set up.All rats were killed after eight-week continuous intervention.Fasting blood glucose (FBG) and fasting insulin (FINS) level were determined.Morphological structure of islet cells and apoptosis were observed.ELISA was used to determine MDA,TNF-α and T-SOD levels in serum and pancreatic tissues and Western blot was used to detect the protein expression levels of total Nrf2 and nulear Nrf2 in pancreatic tissues.Results Compared with NC group,FBG and FINS levels significantly increased and decreased in DM group respectively (all P=0.000).Compared with DM group,FBG and FINS levels significantly decreased and increased in tBHQ group respectively (all P=0.000).Compared with NC group,the number of islet cells significantly decreased and swelling,necrosis and apoptosis occurred in DM group.Islet cells in tBHQ group were significantly better than those in DM group.Compared with NC group,MDA and TNF-α levels in serum and pancreatic tissue significantly increased and TSOD levels significantly decreased in DM group (all P=0.000).Compared with DM group,MDA and TNF-α levels in serum and pancreatic tissue significantly decreased and T-SOD levels significantly increased in DM group(all P=0.000).Total Nrf2 and nulear Nrf2 in protein expression in DM group were significantly lower of than those in NC group (P()=0.000,P nulear Nrf2=0.006).Rats in tBHQ group had significantly higher protein expression of total Nrf2 and nulear Nrf2 than in DM group (all P=0.000).Conclusions Activating Nrf2/ARE pathway can reduce injury of oxidative stress and chronic inflammation on islet B cells further through upregulating the expression of phase Ⅱ detoxifying enzymes and antioxidant enzymes in islet B cells.
2.Advance in Treatment of Spinal Cord Injuries with Schwann Cells Transplantion(review)
Lei XIA ; Hong WAN ; Zhong-cheng WANG
Chinese Journal of Rehabilitation Theory and Practice 2006;12(7):553-555
Schwann cells (SCs) have potently neuroprotective and myelinization abilities. They are one of the earliest and the most frequently used cells that are applied to therapeutic studies in spinal cord injury. At present, SCs are usually used as a platform for therapeutic alliance to integrate various interventions. This review will mainly discuss the issues met in therapeutic alliances with SCs for spinal cord injuries, results of various therapeutic alliances with SCs, positive effects of co-transplantation with SCs on neural stem cells, survival, migration of SCs after transplantation and roles of endogenetic SCs in repairing spinal cord injury.
3.Expression of NALP3 in the spleen of mice with portal hypertension.
Zefeng, XIA ; Guobin, WANG ; Chidan, WAN ; Tao, LIU ; Shuai, WANG ; Bo, WANG ; Rui, CHENG
Journal of Huazhong University of Science and Technology (Medical Sciences) 2010;30(2):170-2
This study examined the mRNA expression of NALP3 in the spleen of the mice with hypersplenism due to portal hypertension (PH). The mouse hypersplenism models were established by oral administration of tetrachloromethane (2 mL/kg/week for 12 weeks by oral gavage). All the mice were randomly divided into a control group and an experimental group. The blood routine test was conducted, spleen index was calculated and spleen was histologically examined. Portal vein sera were taken for detection of the level of uric acid. The mRNA expressions of NALP3 and IL-1beta in the spleen were detected by reverse transcriptase-polymerase chain reaction (RT-PCR). The results showed that the platelet count was significantly lower in the experimental group [(674+/-102)x10(9)/L] than in the control group [(1307+/-181)x10(9)/L] (P<0.05), while the spleen index was significantly higher [(9.83+/-1.36) mug/g] in the experimental group than in the control group [(4.11+/-0.47) mug/g] (P<0.05). The histopathological changes of spleen followed the pattern of congestive splenomegaly. No significant difference was found in the uric acid level in the portal vein between the control group and the experiment group. The mRNA expressions of NALP3 and IL-1beta were up-regulated significantly in the spleen in the experimental group as compared with those in the control group (P<0.05). It was concluded that NALP3 and IL-1beta may play important roles in the pathogenesis of hypersplenism.
4.Change of subunit of NADPH oxidation enzyme complex nox -1 protein in cardiocyte hypoxia - reoxygenation injury and the role of cardiotrophin -1
Lei WAN ; Juxiang LI ; Kui HONG ; Hao DING ; Zirong XIA ; Hai SU ; Sujuan YAN ; Yanqing WU ; Qinghua WU ; Xiaoshu CHENG
Chinese Journal of Pathophysiology 2009;25(11):2113-2117
AIM: To observe the change of subunit of NADPH oxidation enzyme complex nox - 1 protein in cardiocyte hypoxia - reoxygenation injury and the role of cardiotrophin -1.METHODS: Cardiomyocytes from the hearts of 1 -3 d old neonatal rats were prepared by a modified method. Five groups were included in the study: control; hypoxia/ reoxygenation; hypoxia/reoxygenation + CT - 1; CT - 1 + hypoxia/reoxygenation + LY294002 (PIK3/Akt inhibitor) ; CT -1 + hypoxia/reoxygenation + PD98059 (ERK inhibitor) ; CT - 1 + hypoxia/reoxygenation + DMSO. The concentration of CT -1 was 10 μg/L. The survival rate of myocytes was evaluated by MTS method. Apoptosis, mitochondrial permeability transition pore ( △ψm) and reactive oxygen species ( ROS) were detected by flow cytometry. Nox - 1 protein was determined by Western blotting. RESULTS: Apoptosis of cardiomyocytes and the level of ROS (19.7% ±1.4% vs 2.1% ± 0.5% , 14.07% ± 1.25% vs 3.54% ± 0.86% , P < 0.05 ) increased markedly after hypoxia/reoxygenation, but cardio-myocyte survival rate and the level of△ψm (40.55% ±4.25% vs 86.28% ±7.15% , P <0.01) decreased significantly. The expression of nox - 1 protein was upregulated markedly. With CT - 1 intervention, cardiomyocyte survival rate increased markedly, apoptosis, both ROS and expression of nox - 1 protein reduced significantly. The level of△ψm increased obviously. The effect of CT - 1 was inhibited by LY294002.No significant effect was observed on cells survival in DMSO group, which confirmed that LY294002 was specifically involved in blocking the protective effect of CT - 1.CONCLUSION : The expression of subunit of NADPH oxidation enzyme complex nox - 1 protein is upregulated markedly in cardiocyte hypoxia - reoxygenation injury.CT - 1 protects cardiac cells against hypoxia - reoxygenation injury by downregulating the expression of nox -1 protein to decrease the level of ROS.
5.Comparison of RECIST1.1, PERCIST1.0, WHO and EORTC in the evaluation of treatment response in colorectal liver metastases after neoadjuvant chemotherapy
Qian XIA ; Cheng WU ; Linjun TONG ; Yiping SHI ; Dewei TANG ; Chunfeng SHEN ; Liangrong WAN ; Bo XU ; Gang HUANG ; Jianjun LIU
Chinese Journal of Nuclear Medicine and Molecular Imaging 2017;37(9):559-563
Objective To compare treatment response according to the PERCIST1.0,RECIST1.1,EORTC,and WHO criteria in patients with colorectal liver metastases (CLM) who received neoadjuvant chemotherapy.Methods A total of 41 CLM patients (27 males,average age 68.48 years;14 females,average age 62.43 years) from January 2010 to September 2013 were included in this retrospective study.PET/CT scan was performed before chemotherapy and after 4-6 cycles′ chemotherapy.The baseline and the sequential follow-up 18F-FDG PET/CT of each patient were evaluated according to the PERCIST1.0,RECIST1.1,EORTC,and WHO criteria.The response was categorized into 4 levels including CR,PR,SD,PD.PET/CT images were used for both metabolic and anatomic evaluation.The concurrent diagnostic CT or MRI images (performed within 1 week of PET/CT) were also utilized when needed.The agreements of criteria were analyzed using Kappa test.The response rate (RR) and disease control rate (DCR) were compared using χ2 test.Results The RR and DCR according to the PERCIST1.0,EORTC and RECIST1.1 criteria were 31.71%(13/41) and 63.41%(26/41),31.71%(13/41) and 60.98%(25/41),17.07%(7/41) and 68.29%(28/41),respectively.The general comparison of PERCIST1.0 and RECIST1.1,EORTC and RECIST1.1 criteria showed good agreements (κ values: 0.711,0.689).Significant difference was not found in the DCR(χ2=2.000,P>0.05) but found in the RR(χ2=6.000,P<0.05) between PERCIST1.0 and RECIST1.1.Difference of DCR between EORTC and RECIST1.1 was not significant(χ2=3.000,P>0.05),while the RR had significant difference(χ2=6.000,P<0.05).The RR and DCR according to WHO criterion were 12.20%(5/41) and 70.73%(29/41),which had a good consistency with those according to PERCIST1.0 criteria (κ=0.629).Significant statistical difference was not found in the DCR(χ2=3.000,P>0.05) but found in the RR(χ2=8.000,P<0.05) between PERCIST1.0 and WHO criteria.Conclusions In evaluating CLM treatment response,anatomical criteria and metabolic criteria have a good consistency.But metabolic criteria are more sensitive for RR evaluating.
6.PI3K/GSK-3β signaling pathway mediates cardiotrophin-1 cardioprotection against cardiocyte hypoxia-reoxygenation injury
Juxiang LI ; Lei WAN ; Hao DING ; Zirong XIA ; Hai SU ; Sujuan YAN ; Yanqing WU ; Qinghua WU ; Xiaoshu CHENG
Chinese Journal of Emergency Medicine 2009;18(8):814-818
Objective To study the effect of Cardiotrophin-1 (CT-1) on cardiocyte hypoxia-reoxygenation injury,and to investigate the signaling pathways involved in the protective effect. Method This study was carried out in Key Lab of Molecular Medicine in Jiangxi Province. Cardiomyocytes from the hearts of 2-day-old Sprague-Dawley neonatal rats were prepared by a modified method. Five groups were included in the study. Group (ⅰ): control, Group (ⅱ): hypoxia/reoxygeuation, Group (ⅲ): hypoxia / reoxygenation + CT-1, Group (iv) : CT- 1 + hypoxia/ reoxygenation + LY294002 (PIK3/Akt inhibitor), Group (ⅴ): CT-1 + hypoxia / reoxygenation +DMSO. The concentration of CT-1 was 10 ng/mL. Myocytes survival rote was evaluated by MTS method, apopto-sis, mitochondrial permeability transition pore (△ψm) and reactive oxygen species(ROS) were detected by flow cy-tometer, phosphorylased GSK-3β and PI3K protein by western blotting. Analysis of variance and q test as statistical methods was used to analyze the data. Results Cardiomyocyte apoptosis and ROS increased markedly after hy-poxia/reoxygenation,but cardiomyocyte survival rate and the level of △ψm [(40.55±4.25) vs. (86.28±7.15), P < 0.01]decreased significantly. With CT-1 intervention, cardiomyocyte survival rate increased markedly (87%),apoptosis and ROS reduced significantly. The level of △ψm increased, the level of phosphorylased GSK-3β and phosphorylased PI3K protein obviously increased. The effect of CT-1 was inhibited by LY294002, but no significant effect was observed on ceils survival in DMSO group, which confirmed that LY294002 specifically in-volved blocking the protective effect of CT-1. Conclusions CT-1 can protect cardiac cells against hypoxia- reoxy-genation injury, these effects are dependent upon its ability to activate the PI3K/GSK-3β pathway.
7.The effect of HGF on graft-versus-host disease and graft-versus-leukemia after allogeneic bone marrow transplantation in acute lymphoblastic leukemia mice.
Yun-jin XIA ; Qing-ping GAO ; Chu-cheng WAN ; Fan-jun CHENG ; Zhi-xiang LIU ; Ren-ci GUO
Chinese Journal of Hematology 2005;26(7):404-407
OBJECTIVETo investigate the effect of hepatocyte growth factor (HGF) on graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) after allogeneic bone marrow transplantation (allo-BMT) and related mechanism in acute lymphoblastic leukemia (ALL) mice.
METHODSTwenty nude mice were randomly divided into control (group A) and test (group B) groups for monitoring relapse, and 20 BALB/c mice into control (group C) and test (group D) groups for GVHD. HGF as injected from day 0 to day 7 after BMT for groups B and D, while PBS for A and C. CD4(+) and CD8(+) T cell were evaluated by flow cytometry. The survival of mice after BMT was recorded. The level of tumor necrosis factor-alpha (TNF-alpha) was evaluated by ELISA.
RESULTSThe median past-BMT survival were 7.00 +/- 1.58, 9.00 +/- 1.58, 11.00 +/- 3.95 and 24.00 +/- 13.44 days for groups A, B, C, D, respectively, being prolonged in group D. HGF could decrease the quantity of CD4(+) T cells [group D (10.39 +/- 1.15)% vs group C (13.50 +/- 1.80)%, P < 0.01] and increase CD8(+) T cell [group D (12.25 +/- 2.85)% vs group C (6.12 +/- 1.99)%, P < 0.01], decrease the level of TNF-alpha in transplanted ALL mice [group D (112.10 +/- 18.99) pg/ml vs group C (143.90 +/- 25.35) pg/ml, P < 0.01] and reduce the degree of GVHD.
CONCLUSIONHGF could alleviate post-allo-BMT GVHD but retain GVL effect.
Animals ; Bone Marrow Transplantation ; Disease Models, Animal ; Female ; Graft vs Host Disease ; prevention & control ; Graft vs Leukemia Effect ; drug effects ; Hepatocyte Growth Factor ; pharmacology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; immunology ; surgery ; Random Allocation ; Transplantation, Homologous
8.Effects of Triptolide on Expression of Drebrin and Cofilin in Hippocampus of Rats with Alzheimer's Disease
Sai-Sheng ZHANG ; Bao-Lin YANG ; Li-Xia CHENG ; Bin WAN ; Jing NIE ; Xiao-Ling HU ; Cheng LÜ
Chinese Journal of Rehabilitation Theory and Practice 2018;24(1):23-28
Objective To observe the effects of triptolide on drebrin and cofilin expression in the hippocampus of rats with Alzheim-er's disease (AD). Methods Sixty male Sprague-Dawley rats were equally divided into control group, model group and triptolide-treated group with 20 cases in each group. The AD model was established with unilateral injection of beta amyloid 1-40 (Aβ1- 40) into hippocampus in rats. The control group was established with unilateral injection of normal saline with the same volume into hippocampus in rats. The triptolide-treated group was administered triptolide intraperi-toneally, 0.4 mg/kg, once a day, for 15 days after modeling. Spine density of hippocampal neurons was assayed by Golgi staining. Drebrin and cofilin expression of hippocampal neurons was assayed by immunohistochemical staining and reverse transcription polymerase chain reaction (RT-PCR). Results The spine density of hippocampal neurons was higher in the triptolide-treated group than in the model group (P<0.05). The average optical density of drebrin was higher in the triptolide-treated group than in the the model group (P<0.01), while the cell number and average optical density of cofilin were lower (P<0.05). The drebrin mRNA expression was higher in the triptolide-treated group than in the model group (P<0.05), and the cofilin mRNA expression was lower (P<0.01). Conclusion Triptolide may delay the degeneration of dendritic spines in hippocampal neurons of AD rats by regulating the expression of drebrin and cofilin.
9.Respiratory syncytial virus infection promotes the production of thymic stromal lymphopoietin and accelerates Th2 inflammation in mouse airway.
Hu XIA ; Shao-xi CAI ; Wan-cheng TONG ; Li-min LUO ; Hua-peng YU
Journal of Southern Medical University 2009;29(4):724-728
OBJECTIVETo investigate the effect of respiratory syncytial virus (RSV) infection on the production of thymic stromal lymphopoietin (TSLP) and Th1/Th2 balance in asthmatic mice.
METHODSThirty-two female BALB/c mice were randomly divided into 4 groups, namely the PBS group, ovalbumin (OVA) group, RSV group and OVA/RSV group. The mice were sensitized by OVA and then stimulated with nebulized OVA, and RSV was inoculated into the nasal cavity of the mice. BUXCO noninvasive lung function detection was performed to examine the airway response to metacholine, and enzyme-linked immunosorbent assay (ELISA) was used to detect the serum levels of IL-4, IL-5, IL-13, and IFN-gamma in the mice. The cells in the bronchoalveolar lavage fluid (BALF) were counted and classified, and the supernatants of the BALF were used for the detection of TSLP. Histopathological changes in the lung tissues of the mice were examined using HE staining, and immunohistochemistry using anti-mouse TSLP antibody was performed to examine TSLP expressions in the airway epithelial cells.
RESULTSRSV infection promoted the production of TSLP in the asthmatic mice, and the concentration of TSLP in OVA/RSV group (2.13-/+0.05 ng/ml) was significantly higher than that in the other groups (P<0.01). RSV infection increased the serum levels of IL-4, IL-5, IL-13, and IFN-gamma in the mice. The total BALF cells, eosinophils, lymphocytes and neutrophils in OVA/RSV group were significantly higher than those in the other groups; noninvasive lung function examination showed higher Penh value in OVA/RSV group (318.66-/+50.87) than in the other groups when the inhaled metacholine increased to 6.25 mg/ml (P<0.01). More obvious and extensive airway inflammatory cell infiltration in OVA/RSV group were observed, and immunohistochemical staining also showed higher expression of TSLP in the airway epithelial cells of OVA/RSV group.
CONCLUSIONSRSV infection promotes the production of TSLP in the airway epithelial cells and increases the level of Th2 cytokines in asthmatic mice. Concurrent RSV infection can exacerbate Th2 inflammatory reaction in asthmatic mice.
Animals ; Bronchoalveolar Lavage Fluid ; Cytokines ; biosynthesis ; secretion ; Female ; Immunohistochemistry ; Inflammation ; immunology ; virology ; Interferon-gamma ; blood ; Interleukins ; blood ; Lung ; immunology ; metabolism ; virology ; Mice ; Mice, Inbred BALB C ; Respiratory Syncytial Virus Infections ; blood ; immunology ; metabolism ; Th2 Cells ; cytology ; immunology ; virology
10.Plasma concentrations of vascular endothelial growth factor and tissue factor in children with acute lymphoblastic leukemia.
Hua-Qiang YANG ; Rong-Huan ZHANG ; Zheng-Hua ZHANG ; Chu-Cheng WAN ; Yun-Jin XIA
Chinese Journal of Contemporary Pediatrics 2007;9(6):526-528
OBJECTIVETo detect plasma concentrations of vascular endothelial cell growth factor (VEGF) and tissue factor (TF) in children with acute lymphoblastic leukemia (ALL) and explore their clinical significance in ALL.
METHODSThirty-three children with newly diagnosed ALL, including 18 cases of low risk, 7 cases of moderate risk and 8 cases of high risk, were enrolled in this study. Twenty-five patients received a complete remission and 8 cases were in non-remission after conventional remission induction chemotherapy. Plasma concentrations of VEGF and TF in the patients were detected using ELISA before and after treatment. Sixteen healthy children served as normal control group.
RESULTSPlasma concentrations of VEGF and TF in ALL patients before treatment were significantly higher than those in normal controls (P < 0.01). Plasma concentrations of VEGF and TF in the non-remission group before treatment were significantly higher than those in the remission group (P < 0.05) and the control group (P < 0.01). After treatment the plasma concentrations of VEGF and TF in the non-remission group were not significantly reduced and higher than those in the remission and the control groups (P < 0.01). There were significant differences in plasma concentrations of VEGF and TF among the low-risk, moderate-risk and high-risk groups before and after treatment (P < 0.05). Plasma concentrations of VEGF and TF in the high risk group were not significantly reduced after treatment and higher than those in the control group (P < 0.01). A linear correlation was noted between plasma VEGF and TF concentrations in ALL patients before treatment (r=0.50, P < 0.01).
CONCLUSIONSVEGF and TF play an important role in the development of ALL and may be useful to the evaluation of the severity and the outcome in ALL.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; blood ; etiology ; Thromboplastin ; analysis ; Vascular Endothelial Growth Factor A ; blood