1.Lovastatin derivative dehydrolovastatin ameliorates ulcerative colitis in mice by suppressing NF-κB and inflammatory cytokine expression
Xu ZHANG ; Qing Hua DENG ; Jian Hua DENG ; Sheng Ju WANG ; Qiu CHEN
The Korean Journal of Physiology and Pharmacology 2020;24(2):137-147
Ulcerative colitis (UC) is associated with intestinal immune imbalance and inflammatory response. Because dehydrolovastatin (DLVT), a derivative of lovastatin, has been recently shown to inhibit inflammation and relieve immune arthritis induced by chemical stimuli, we studied its effect and possible mechanism on UC induced by dextran sulfate sodium. The BALB/c mice were classified into six groups: normal control group, model group, DLVT high dose group, DLVT low dose group, salazosulfapyridine (SASP) group and lovastatin (LVT) group. The disease activity indices of UC and pathological changes were investigated. The myeloperoxidase (MPO) activity in colon tissue and inflammatory factors such as IL-6, IL-10, IL-17, and TNF-α in the serum were analyzed by ELISA, while the expression of NF-κB p65 protein in colon tissue was detected by immunohistochemistry and western blot. DLVT relieved the disease activity indices and pathological damage of the UC mice. Furthermore, DLVT significantly decreased MPO activity and improved the imbalance of inflammatory cytokines through inhibiting the expression of NF-κB p65. Meanwhile, the positive drug of SASP has a similar effect to DLVT, but the effect of DLVT in both decreasing IL-17, TNF-α, and increasing IL-10 was significantly stronger than that of SASP. These results suggest that DLVT may ameliorates the symptoms of UC.
2.Lovastatin derivative dehydrolovastatin ameliorates ulcerative colitis in mice by suppressing NF-κB and inflammatory cytokine expression
Xu ZHANG ; Qing Hua DENG ; Jian Hua DENG ; Sheng Ju WANG ; Qiu CHEN
The Korean Journal of Physiology and Pharmacology 2020;24(2):137-147
Ulcerative colitis (UC) is associated with intestinal immune imbalance and inflammatory response. Because dehydrolovastatin (DLVT), a derivative of lovastatin, has been recently shown to inhibit inflammation and relieve immune arthritis induced by chemical stimuli, we studied its effect and possible mechanism on UC induced by dextran sulfate sodium. The BALB/c mice were classified into six groups: normal control group, model group, DLVT high dose group, DLVT low dose group, salazosulfapyridine (SASP) group and lovastatin (LVT) group. The disease activity indices of UC and pathological changes were investigated. The myeloperoxidase (MPO) activity in colon tissue and inflammatory factors such as IL-6, IL-10, IL-17, and TNF-α in the serum were analyzed by ELISA, while the expression of NF-κB p65 protein in colon tissue was detected by immunohistochemistry and western blot. DLVT relieved the disease activity indices and pathological damage of the UC mice. Furthermore, DLVT significantly decreased MPO activity and improved the imbalance of inflammatory cytokines through inhibiting the expression of NF-κB p65. Meanwhile, the positive drug of SASP has a similar effect to DLVT, but the effect of DLVT in both decreasing IL-17, TNF-α, and increasing IL-10 was significantly stronger than that of SASP. These results suggest that DLVT may ameliorates the symptoms of UC.
3. Comparative study of the chitooligosaccharides effect on the proliferation inhibition and radiosensitization of three types of human gastric cancer cell line
Yang LUO ; Liang DENG ; Qiu-Ju DENG ; Li WEN
Asian Pacific Journal of Tropical Medicine 2016;9(6):601-605
Objective To observe the chitooligosaccharides (COS) effect on the proliferation inhibition and radiosensitivity of three types of human gastric cancer cell line. Mothods CCK-8 assay was employed to obtain the inhibition ratio of COS on BGC823 cells, MKN45 cells and SGC7901 cells at 48 h after treatment and the proliferation-inhibition curve was drawn with the inhibition ratio of COS on three types of cells. The clonogenic assay was used to detect the cell viability of 0, 1, 2, 4, 6 and 8 Gy (6 dose grades) in RAY group and RAY + COS group after X-ray, and the cell survival curve was used to analyze the sensitization enhancement ratio of COS. Flow cytometry was employed to detect cell cycle and apoptosis rate in control group, RAY group and RAY + COS group after 48 h treatment. Results COS inhibited the proliferation of three types of cells. The inhibition rate was positively correlated with the concentration of COS, and the susceptibility of MKN45 cells, SGC7901 cells and BGC823 cells to COS decreased in turn. The cell viability decreased gradually with the increasing radiation dose in RAY group and RAY + COS group (P < 0.01). The cell viabilities of RAY + COS group were lower than those of RAY group at all the dose grades under X-ray exposure (P < 0.01), and the sensitization enhancement ratios of COS on BGC823 cells, MKN45 cells and SGC7901 cells were 1.06, 1.28 and 1.15, respectively. In controlled trials, apoptosis rate and percentage in the G
4.Association of TNF-alpha-238G/A and 308 G/A gene polymorphisms with pulmonary tuberculosis among patients with coal worker's pneumoconiosis.
Hong-Min FAN ; Zhuo WANG ; Fu-Min FENG ; Kong-Lai ZHANG ; Ju-Xiang YUAN ; Hong SUI ; Hong-Yan QIU ; Li-Hua LIU ; Xiao-Juan DENG ; Jing-Xue REN
Biomedical and Environmental Sciences 2010;23(2):137-145
OBJECTIVESTumor necrosis factor-alpha (TNF-alpha) may play an important role in host's immune response to mycobacterium tuberculosis (M. tuberculosis) infection. This study was to investigate the association of TNF-alpha gene polymorphism with pulmonary tuberculosis (TB) among patients with coal worker's pneumoconiosis (CWP).
METHODSA case-control study was conducted in 113 patients with confirmed CWP complicated with pulmonary TB and 113 non-TB controls with CWP. They were matched in gender, age, job, and stage of pneumoconiosis. All participants were interviewed with questionnaires and their blood specimens were collected for genetic determination with informed consent. The TNF-alpha gene polymorphism was determined with polymerase chain reaction of restriction fragment length polymorphism (PCR-RFLP). Frequency of genotypes was assessed for Hardy-Weinberg equilibrium by chi-square test or Fisher's exact probability. Factors influencing the association of individual susceptibility with pulmonary TB were evaluated with logistic regression analysis. Gene-environment interaction was evaluated by a multiplicative model with combined OR. All data were analyzed using SAS version 8.2 software.
RESULTSNo significant difference in frequency of the TNF-alpha-308 genotype was found between CWP complicated with pulmonary TB and non-TB controls (chi2 = 5.44, P = 0.07). But difference in frequency of the TNF-alpha-308 A allele was identified between them (chi2 = 5.14, P = 0.02). No significant difference in frequencies of the TNF-alpha-238 genotype and allele (P = 0.23 and P = 0.09, respectively) was found between cases and controls either, with combined (GG and AA) OR of 3.96 (95% confidence interval of 1.30-12.09) at the -308 locus of the TNF-alpha gene, as compared to combination of the TNF-alpha-238 GG and TNF-alpha-308 GG genotypes. Multivariate-adjusted odds ratio of the TNF-alpha-238 GG and TNF-alpha-308 GA genotypes was 1.98 (95% CI of 1.06-3.71) for risk for pulmonary TB in patients with CWP. There was a synergic interaction between the TNF-alpha-308 GG genotype and body mass index (OR = 4.92), as well as an interaction between the TNF-alpha-308 GG genotype and history of BCG immunization or history of TB exposure. And, the interaction of the TNF-alpha-238 GG genotype and history of BCG immunization or TB exposure with risk for pulmonary TB in them was also indicated.
CONCLUSIONSTNF-alpha-308 A allele is associated with an elevated risk for pulmonary TB, whereas TNF-alpha-238 A allele was otherwise.
Aged ; Aged, 80 and over ; Anthracosis ; complications ; Case-Control Studies ; Environmental Exposure ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Logistic Models ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Promoter Regions, Genetic ; Tuberculosis, Pulmonary ; genetics ; Tumor Necrosis Factor-alpha ; genetics
6.Effect of graft-versus-host disease on relapse and survival in 100 patients after allogeneic hematopoietic stem cell transplantation.
Xue-Rong DENG ; Han-Yun REN ; Xi-Nan CEN ; Li-Hong WANG ; Ze-Yin LIANG ; Wen-Sheng WANG ; Zhi-Xiang QIU ; Jin-Ping OU ; Wei-Lin XU ; Mang-Ju WANG ; Yuan LI ; Yue YIN
Journal of Experimental Hematology 2009;17(4):994-998
The study was aimed to investigate the incidences and risk factors of acute and chronic graft-versus-host diseases (GVHD) and to clarify their effects on relapse and survival of recipients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The clinical data of 100 cases of allo-HSCT were retrospectively analyzed. The incidences and risk factors of aGVHD and cGVHD, relapse and survival were studied. The results showed that 31 cases developed aGVHD of II - IV grade (34.4%) and 14 cases developed aGVHD of III - IV grade (17.7%). HLA matched or mismatched did not show significant difference in the development of aGVHD of II - IV grade (p > 0.05). Previous occurrence of aGVHD was the risk factor for cGVHD (HR = 2.303, p = 0.088). The female was a favorable factor for cGVHD (HR = 0.401, p = 0.055). The relapse rate was lower in patients who developed cGVHD. The development of aGVHD of II - IV grade was the risk factor for overall survival (p < 0.05). The mortality of patients with aGVHD of III - IV grade and mortality of patients with aGVHD of 0 - I grade were 81.0% and 35.7% respectively, there was very significant difference between them (p = 0.000). In conclusion, till now GVHD and graft-versus-leukemia (GVL) effect can not be separated. The positive effect of GVL could be counteracted by GVHD-related mortality. It is necessary to prevent and control the development of severe aGVHD. The development of local cGVHD may be beneficial to the long-term disease-free survival of patients after allo-HSCT.
Adolescent
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Adult
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Child
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Child, Preschool
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Disease-Free Survival
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Female
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Graft vs Host Disease
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etiology
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mortality
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Hematopoietic Stem Cell Transplantation
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adverse effects
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mortality
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Humans
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Incidence
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Male
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Middle Aged
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Recurrence
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Retrospective Studies
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Risk Factors
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Young Adult
7.Predictive value of left ventricular ejection fraction reserve assessed by SPECT G-MPI for major adverse cardiovascular event in patients with coronary artery disease.
Yi Han ZHOU ; Yao LU ; Jing Jing MENG ; Tian Tian MOU ; Yu Jie BAI ; Shuang ZHANG ; Ya Qi ZHENG ; Qiu Ju DENG ; Jian JIAO ; Zhi CHANG ; Xiao Fen XIE ; Ming Kai YUN ; Hong Zhi MI ; Xiang LI ; Xiao Li ZHANG
Chinese Journal of Cardiology 2023;51(6):626-632
Objective: To evaluate the prognostic value of left ventricular ejection fraction (LVEF) reserve assessed by gated SPECT myocardial perfusion imaging (SPECT G-MPI) for major adverse cardiovascular event (MACE) in patients with coronary artery disease. Methods: This is a retrospective cohort study. From January 2017 to December 2019, patients with coronary artery disease and confirmed myocardial ischemia by stress and rest SPECT G-MPI, and underwent coronary angiography within 3 months were enrolled. The sum stress score (SSS) and sum resting score (SRS) were analyzed by the standard 17-segment model, and the sum difference score (SDS, SDS=SSS-SRS) was calculated. The LVEF at stress and rest were analyzed by 4DM software. The LVEF reserve (ΔLVEF) was calculated (ΔLVEF=stress LVEF-rest LVEF). The primary endpoint was MACE, which was obtained by reviewing the medical record system or by telephone follow-up once every twelve months. Patients were divided into MACE-free and MACE groups. Spearman correlation analysis was used to analyze the correlation between ΔLVEF and all MPI parameters. Cox regression analysis was used to analyze the independent factors of MACE, and the optimal SDS cutoff value for predicting MACE was determined by receiver operating characteristic curve (ROC). Kaplan-Meier survival curves were plotted to compare the difference in the incidence of MACE between different SDS groups and different ΔLVEF groups. Results: A total of 164 patients with coronary artery disease [120 male; age (58.6±10.7) years] were included. The average follow-up time was (26.5±10.4) months, and a total of 30 MACE were recorded during follow-up. Multivariate Cox regression analysis showed that SDS (HR=1.069, 95%CI: 1.005-1.137, P=0.035) and ΔLVEF (HR=0.935, 95%CI: 0.878-0.995, P=0.034) were independent predictors of MACE. According to ROC curve analysis, the optimal cut-off to predict MACE was a SDS of 5.5 with an area under the curve of 0.63 (P=0.022). Survival analysis showed that the incidence of MACE was significantly higher in the SDS≥5.5 group than in the SDS<5.5 group (27.6% vs. 13.2%, P=0.019), but the incidence of MACE was significantly lower in the ΔLVEF≥0 group than in theΔLVEF<0 group (11.0% vs. 25.6%, P=0.022). Conclusions: LVEF reserve (ΔLVEF) assessed by SPECT G-MPI serves as an independent protective factor for MACE, while SDS is an independent risk predictor in patients with coronary artery disease. SPECT G-MPI is valuable for risk stratification by assessing myocardial ischemia and LVEF.
Humans
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Male
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Middle Aged
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Aged
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Coronary Artery Disease/diagnostic imaging*
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Stroke Volume
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Myocardial Perfusion Imaging
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Retrospective Studies
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Ventricular Function, Left
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Myocardial Ischemia