1.Protective effect of Polydatin against rat cortex mitochondria injury induced by ?OH
Jingwei TIAN ; Jianxiong YANG ; Fenghua FU ; Wanglin JIANG ; Zhenhua WANG ; Chaoyu WANG
Chinese Pharmacological Bulletin 2003;0(11):-
AIM To study the effects of polydatin on free radical induced rat cortex mitochondria injury. METHODS Fe 2++VitC system was used to produce ?OH. The mitochondria was isolated. Mitochondria membrane fluidity, swelling and contents of phospholipid were determined to measure the function of mitochondria membrane. The activities of ATPase and Cytochrome C oxidase were determined to measure the ability of mitochondria energy metabolism. The activity of superoxide dismutase (SOD) and content of malondial dehyde (MDA) were determined to measure the ability of anti oxygenation. RESULTS ?OH resulted in severe neuronal mitochondria injuries and the injuries and the injuries was alleviated by Polydatin (content of 100,200,400 mg?L -1). The swelling of mitochondria was ameliorated, the decomposability of mitochondrion membrane phospholipid was decreased, the membrane fluidity of mitochondria was increased. Polydatin also significantly inhibited the decrease in SOD, Cytochrome C oxidase and ATPase activity and the increase in MDA levels caused by free radical. CONCLUSION Polydatin has a protective action against the rat neuronal mitochondria injuries induced by oxygen free radical. The mechanisms may be derived from scavenging free radicals, reducing lipid peroxides, and improving the energy metabolism.
2.The trend and value of 18F-FDG PET/CT included in the criteria for liver transplantation in hepatocellular carcinoma
Chaoyu PU ; Jianjie WANG ; Li ZHOU
Journal of Clinical Hepatology 2020;36(2):421-425
Liver transplantation is an effective method for the treatment of hepatocellular carcinoma (HCC). In order to reduce the high recurrence rate of tumor after liver transplantation for HCC, some scholars put forward the famous Milan criteria. Since the Milan criteria are too strict, some HCC patients with relatively “good biological behavior” and large lesions or multiple nodules are excluded from the waiting list for liver transplantation, and thus a large number of “expanded versions of the Milan criteria” appeared around the world. As for the histopathology of HCC, microvascular invasion (MVI) and poorly differentiated tumor tissue are significantly associated with the high recurrence rate after liver transplantation for HCC. This article reviews and summarizes the articles on the application of 18F-FDG PET/CT in liver transplantation for HCC in China and foreign countries and points out that the uptake of 18F-FDG in HCC lesions reflects the difference in the biological behavior (i.e., invasion) of tumor tissue. The intense uptake of 18F-FDG is positively correlated with MVI and poor differentiation of HCC. In addition, 18F-FDG can detect extrahepatic metastatic lesions sensitively and accurately. Preoperative 18F-FDG PET/CT findings have a high value in predicting the prognosis of liver transplantation for HCC, and it is a trend to incorporate such findings into the criteria for liver transplantation in HCC. It is also expected to unify the various expanded versions of the Milan criteria. The new criteria for liver transplantation may be defined as follows: the Milan criteria should be followed in general; as for the patients who do not meet the Milan criteria, liver transplantation can be performed for those who have lesions with negative 18F-FDG PET/CT results, without the involvement of major blood vessels or extrahepatic metastasis.
3.Clinical analysis of autologous peripheral blood hematopoietic stem cell mobilization regimen in 61 lymphoma patients
Chaoyu WANG ; Bing XIA ; Wen XU ; Chen TIAN ; Haifeng ZHAO ; Hongliang YANG ; Zhigang ZHAO ; Xiaofang WANG ; Yafei WANG ; Yong YU ; Yizhuo ZHANG
Chinese Journal of Clinical Oncology 2017;44(8):377-383
Objective:To compare the efficacy between chemotherapy with granulocyte colony-stimulating factor (G-CSF) and chemo-therapy with G-CSF and granulocyte-macrophage colony-stimulating factor (GM-CSF) for the mobilization of peripheral blood hemato-poietic stem cells and hematological recovery post-transplantation in patients with malignant lymphoma. Methods:Autologous pe-ripheral blood hematopoietic stem cell mobilization data of 61 malignant lymphoma patients who were treated with chemotherapy plus G-CSF or chemotherapy plus G-CSF and GM-CSF from May 2008 to October 2016 were included in this study. The mobilization effi-cacy and hematopoietic recovery were analyzed. Results:During mobilization, White blood cells (WBC) of all patients decreased to 1.0×109/L and platelets (PLT) dropped to 40×109/L. The successful mobilization rates of CD34+cell are 52.5%in chemotherapy plus G-CSF group and 90.5%in chemotherapy plus G-CSF+GM-CSF group (P=0.003). All patients successfully underwent hematopoietic recon-struction without transplantation-related mortality. Conclusion: Although chemotherapy with G-CSF+GM-CSF can significantly in-crease the effect of autologous peripheral blood hematopoietic stem cell mobilization, the reconstruction of hematopoietic function after transplantation and side reaction between the two groups are the same. Thus, chemotherapy with G-CSF+GM-CSF is not superior to chemotherapy with G-CSF in mobilizing autologous peripheral blood hematopoietic stem cells.
4.Effects of liver-specific Nampt knockout on ischemic stroke
Shengli QING ; Shuna WANG ; Dongsheng WANG ; Xiaoqun LYU ; Tianying XU ; Chaoyu MIAO
Journal of Pharmaceutical Practice 2022;40(1):12-19
Objective Nicotinamide phosphoribosyltransferase (Nampt) is a new therapeutic target for ischemic stroke. The aim of this study was to investigate protective effect of liver-derived Nampt on ischemic stroke. Methods Liver-specific Nampt knockout mice were generated using the Cre/loxP system. NamptloxP/loxP mice were crossed with liver-specific Cre recombinase expression mice (Alb-Cre), and the progeny genotypes were identified by polymerase chain reaction. Body weight of knockout mice and control mice were measured. Nampt in liver and brain was determined by Western blot assay. Middle cerebral artery occlusion (MCAO), a classical ischemic stroke model, was generated in liver-specific Nampt knockout mice and control mice by electrocoagulation. After 24 h of modeling, neurological deficit scores of each group were evaluated and TTC staining was performed to determine the cerebral infarction volume. The level of plasma Nampt in each group was determined by ELISA. Results Liver-specific Nampt knockout mice with the genotype of NamptloxP/loxPAlb-Cre were successfully constructed. The hepatic Nampt expression in knockout mice was significantly decreased by 74.2% compared to control mice, while there was no significant difference in the expression of brain Nampt protein between the knockout group and the control group. Specific knockout of liver Nampt gene expression had no effect on the body weight of mice. Under normal physiological conditions, there was no significant difference in plasma Nampt levels between liver-specific Nampt knockout mice and control mice of the same gender. 24 h after MCAO modeling, there were no significant differences in neurological deficit scores, cerebral infarct volume and plasma Nampt concentration between liver-specific Nampt knockout group and control group. Conclusion Liver-specific Nampt knockout mice are successfully constructed. Liver-derived Nampt has no significant protective effects on ischemic stroke.
5.Establishment of finite element model of ankle joint and its biomechanical study
Xingjun LI ; Chaoyu BAO ; Hua LI ; Weihao WANG ; Shuying LI ; Di WU
Chinese Journal of Trauma 2018;34(9):827-832
Objective The three-dimensional finite element model of the normal ankle joint was established to simulate the changes of stress and displacement under stress from different directions and of different magnitudes so as to provide a theoretical basis for the biomechanical mechanism of the ankle joint injury.Methods Spiral CT scan was performed on the left ankle of a 30 year old healthy male volunteer to obtain the original CT image data.The three-dimensional digital model of ankle joint generated by Mimics and Geomagic softwares was imported into the software Ansys.The three-dimensional finite element model of ankle joint with complete anatomical structure was obtained after the main steps of meshing,central node,element linking and module loading using finite element method.Stress from different directions and of different magnitudes were loaded unto the model.The stress changes were measured by foot stress distribution measurement system.The stress changes,displacement change distribution,the stress peak value of heel are,metatarsal stress,and plantar contact stress area as well as the maximum,minimum,and contact are of the tibial articular surface contact stress were compared between the finite element model and the volunteer himself to verify the consistency.Results For the finite element model of normal ankle joint,the plantar peak stress was [(0.33 ± 0.10) MPa],the metatarsal stress was [(0.13 ± 0.21)MPa],the foot contact stress area was [(78.60 ±0.32)mm2],the tibial articular surface maximum contact stress was [(2.72 ± 0.10) MPa],the minimum contact stress was [(1.35 ±0.12)MPa],and the contact stress area was [(79.1 ± 0.14)mm2].For the volunteer,double foot plantar peak stress was [(0.35 ± 0.12)MPa],the metatarsal stress [(0.13 ±0.16)MPa],the foot contact stress area was [(77.3 ± 0.42)mm2],the tibial articular surface maximum contact stress was [(2.79 ± 0.23) MPa],the minimum contact stress was [(1.37 ± 0.20) MPa],and the contact stress area was [(79.10 ±0.14)mm2] (P <0.05).Therefore,the three finite element model of ankle joint was basically consistent with the real human ankle joint because of the similiar distribution,trend,and values.Conclusion The three-dimensional finite element model of normal ankle joint can objectively reflect the anatomical structure and biomechanical characteristics of the joint,which is of great value to understand the changes of the internal mechanics and ankle joint injury.
6.Research progress on animal model and potential therapeutic strategy in intracere-bral hemo rrhage
Chunchun WEI ; Pei WANG ; Chaoyu MIAO
Journal of Pharmaceutical Practice 2016;34(4):297-300,376
Intracerebral hemorrhage (ICH) refers to bleeding within the brain parenchyma due to the rupture of blood vessels ,and is a highly lethal stroke subtype ,accounting for nearly 10%-15% of all strokes .The morbidity and mortality of ICH are very high and its pathophysiological mechanisms are currently not fully understood .Therefore ,based on current clini-cal evidence-based medicine ,there is no definite and effective medical treatment that can improve the prognosis and survival of patients available yet .As an important tool for basic research ,the development and application of the ICH animal model pro-moted the understanding of the pathophysiological mechanisms and molecular mechanisms leading to brain injury by ICH .Re-cently ,the ICH animal model studies contributed to a number of proposed potential therapeutic strategies ,such as the inhibi-tion of thrombin and the reduction of pro-inflammatory pathways .In addition ,recent research of stem cells suggested that cell transplantation therapy for the treatment of ICH may also have good prospects .In this review ,we discuss the development and application of animal models for studies on ICH and the advances regarding the potential therapeutic strategies for ICH .
7.Establishment and evaluation of in vivo and in vitro D-galactose induced cognitive impairment models
Chen HONG ; Wenjun HU ; Shuna WANG ; Zhiyong LI ; Chaoyu MIAO
Journal of Pharmaceutical Practice 2019;37(1):14-18,73
Objective To construct and explore the in vivo and in vitro D-galactose induced cognitive impairment models and evaluate the application value of the combined models in the study of cognitive impairments.Methods The cognitive impairment mice model induced by D-gal was prepared by continuous intraperitoneal injection of D-gal saline solution for 8weeks, followed by detection of learning and memory functions with Morris water maze.The related molecular markers in the brain tissue were assayed to evaluate the effect and application value.D-gal cell model was prepared by adding D-gal in different concentrations into the cell cultural medium of neurons harvested from the hippocampus of young mice.The effect and application value were evaluated by detecting the molecular markers related to the level of cell injury.Results The Morris water maze on the D-gal model showed that the learning and memory functions of mice in the model group were significantly lower than those in the control group.Meanwhile, the levels of apoptosis and oxidative stress in the model group were significantly higher than those in the control group.In the hippocampal neuron model of D-gal, the neurons showed a dose-dependent morphologic and functional change with the increase of D-gal dose and the levels of apoptosis and oxidative stress were significantly higher than those in the negative control.Conclusion D-galactose can be successfully used to induce cognitive impairment models both in vivo and in vitro through the decrease of the learning and memory functions of mice and induction of apoptosis and oxidative stress in neurons.Combined application of the two models of D-gal can be one of effective and promising tools for the study of cognitive impairment and pharmacodynamic evaluation.
8.Clinical analysis of autologous peripheral blood hematopoietic stem cell mobilization regimen in 56 multiple myeloma patients
Xia BING ; Chaoyu WANG ; Wen XU ; Chen TIAN ; Haifeng ZHAO ; Zhigang ZHAO ; Xiaofang WANG ; Yafei WANG ; Yong YU ; Yizhuo ZHANG
Chinese Journal of Clinical Oncology 2018;45(11):557-561
Objective: To compare the efficacy between chemotherapy plus granulocyte colony-stimulating factor (G-CSF) and chemotherapy plus G-CSF and granulocyte-macrophage colony-stimulating factor (GM-CSF) for the mobilization of peripheral blood stem cells (PBSC) and hematopoietic recovery after transplantation in patients with multiple myeloma (MM). Methods: A retrospective study of autologous PBSC (APBSC) mobilization data of 56 MM patients who were treated with chemotherapy plus G-CSF or chemotherapy plus G-CSF and GM-CSF from May 2008 to July 2016 in Tianjin Medical University Cancer Institute and Hospital was conducted. The mobilization efficacy and hematopoietic recovery were analyzed. Results: In the univariate analysis, the successful collection rate of a single harvest in women and in patients with ISS stage Ⅲ and R-ISS stage Ⅱ/Ⅲ and treated with chemotherapy plus G-CSF was lower (P<0.05). However, age (≤60 years vs.>60 years), subtype, D-S staging (Ⅰ+Ⅱvs.Ⅲ), number of cycles of chemotherapy before mobilization (≤6 cycles vs.>6 cycles), disease phase before mobilization (PR vs. CR), and interval between diagnosis and mobilization (≤18 months vs.>18 months) were not correlated with CD34+ cell collection and successful mobilization rates (P>0.05). In the multivariate model, the successful mobilization rate in patients who received the chemotherapy plus G-CSF and GM-CSF mobilization regimen was higher (OR=12.009, 95% CI=1.961-73.537). The effect of mobilization regimens remained significant (P=0.007). Hematopoietic recovery without transplantation-related mortality occurred successfully in all patients. Conclusions: Chemotherapy plus G-CSF and GM-CSF mobilization regimens can significantly increase the effect of APBSC mobilization and ensure the recovery of hematopoietic function after transplantation. Chemotherapy plus G-CSF and GM-CSF mobilization regimens are safe and effective for mobilizing APBSCs.
9.Ibrutinib inhibits diffuse large B-cell lymphoma cell survival
WU DONGWEI ; XIA BING ; WU LING ; XU WEN ; NING QIAOYANG ; YUAN TIAN ; WANG CHAOYU ; JIN XIN ; YU YONG ; ZHANG YIZHUO
Chinese Journal of Clinical Oncology 2017;44(18):903-908
Objective:To illustrate the effect and mechanism of ibrutinib,a Bruton's tyrosine kinase(BTK)inhibitor that inhibits diffuse large B-cell lymphoma(DLBCL)cell survival.Methods:DLBCL cell lines SUDHL-10 and HBL-1 were treated with ibrutinib at different concentrations.A MTT assay was used to detect the inhibition of cell proliferation.Cell apoptosis was analyzed by Annexin V-binding assay,as well as flow cytometry and DAPI staining.The expression of phosphorylated BTK,AKT and ERK was detected by Western blot. DLBCL cells were co-cultured with MSC.The inhibitory effect of ibrutinib on DLBCL cells in tumor microenvironment was assessed in clonogenicity in vitro and in a tumor-bearing non-obese diabetic/severe combined immunodeficient mice in vivo.Results:Up to 2.5 μmol/L and high concentrations of ibrutinib significantly inhibited the proliferation of DLBCL cells in a dose-dependent manner.Approx-imately 1 and 2.5 μmol/L ibrutinib was added on SUDHL-10 cells for 24 h,and the cell apoptotic rates were(21.73±3.64)% and(34.71± 2.36)%,respectively.Both were superior to that of the control group(3.55±1.89)%(P<0.05).Both two DLBCL cell lines pretreated with 5 and 10 μmol/L ibrutinib for 24 h and exhibited nuclear shrinkage at 5 μmol/L and nuclear fragmentation at 10 μmol/L.The expres-sion of phosphorylated BTK,AKT,and ERK decreased significantly after ibrutinib treatment.Ibrutinib inhibited clonogenicity in vitro(P<0.01)and cell proliferation and growth in vivo of DLBCL cells in co-culture system.The differences were statistically significant.Conclu-sion:Ibrutinib can inhibit the proliferation and induce apoptosis of SUDHL-10 and HBL-1 cell lines through a mechanism of blocking the AKT and ERK signaling pathways,as well as the proliferation of DLBCL cells in tumor microenvironment.This finding can significant-ly benefit DLBCL treatment.
10.Effect of nicotinamide mononucleotide on mortality of mice with endotoxic shock
Dongsheng WANG ; Sili ZHENG ; Minghe CHENG ; Chaoyu MIAO
Journal of Pharmaceutical Practice 2021;39(2):134-137
Objective To study the effect of nicotinamide mononucleotide (NMN) on the mortality of the lipopoly-saccharide (LPS)-induced endotoxic shock mouse model. Methods 10-week-old C57BL/6J male mice were randomly divided into groups, and were injected intraperitoneally (i.p.) with LPS (10 mg/kg) to induce endotoxic shock models. NMN was i.p. injected in three ways: (1) 0.5 h after modeling, doses of 10, 30, 100 and 300 mg/kg; (2) 0.5 h before modeling, doses of 30, 100, 300 and 600 mg/kg; or (3) 0.5 and 12 h after modeling, dose of 300 mg/kg each time. The death times of each group were recorded, and the survival curves were drawn. Results Compared with the solvent control group, NMN at different doses given 0.5 h after or before modeling didn’t improve the survival rate or delay the death time of endotoxic shock mice; But when given at 0.5 and 12 h 300 mg/kg after modeling, NMN accelerated the death of mice and increased the mortality of mice. NMN products by two manufacturers showed similar effects. Conclusion NMN has no therapeutic effect on LPS-induced endotoxic shock, and repeated administration of NMN after endotoxic shock will increase the mortality.