3.Effects of the total flavonoids of scutellaria barbataon on atherosclerosis and expression of PLTP in ApoE gene deficiency mice
Pingting ZHU ; Yun SUN ; Zhaoguo LIU ; Yuping LIU ; Ping BU
Chinese Pharmacological Bulletin 2015;(6):833-837,838
Aim To observe the effects of the total fla-vonoids of scutellaria barbataon ( TFSB ) on high-fat
feeding ApoE gene deficiency mice in early atheroscle-rosis ( AS ) and its underlying mechanisms. Methods
40 ApoE-/ -male mice were divided into five groups:model group, SIM group and L-TFSB, M-TFSB, H-TFSB group, 5 C57BL/6J mice were selected as nor-mal control group. All mice in experimental group were fed with high-lipid diet for 4 weeks and all mice were killed after 8 weeks. H&E staining was used to observe morphology of aorta. Blood rheometer was used to ex-amine plasm viscosity and whole blood viscosity. Fully automatic biochemical analyser was used to detect the serum levels of TG, TC, LDL-C and HDL-C. The ex-pression levels of PLTP and VE in serum were meas-ured by ELISA. The expression levels of PLTP and FXR in liver were examined by Western blot. Results The model was established successfully. TFSB groups could improve the aorta AS morphology of model mice and significantly reduce the serum levels of TG, TC and LDL-C, while increase the level of HDL-C ( P<0. 05 or P<0. 01 ) . TFSB groups could decrease the
hematocrit value, plasma viscosity and whole blood vis-cosity of AS model mice significantly and had statistical significance when compared with model group ( P <0. 01 ) . The expression levels of PLTP of serum were reduced significantly when compared with model group ( P <0. 01 ) . We also found that the expression of PLTP was in negative correlation with VE ( r = -0. 675,P<0. 01). M-TFSB and H-TFSB group could decrease the expressions of PLTP and FXR of liver when compared with model group ( P <0. 01 ) . Con-clusion TFSB may exert its anti-AS effect partly through inhibiting the levels of FXR and PLTP of ApoE-/ -mice, increasing the level of VE, regulating blood lipids, improving blood rheology and reducing the damage of AS in mice.
4.A mete-analysis of the association of apoE gene polymorphisms and gallstone
Zhaoguo LIU ; Wenyuan SONG ; Ming LV ; Yong ZHANG ; Guozhen FU
Chinese Journal of Hepatobiliary Surgery 2011;17(5):397-400
Objective To evaluate the relationship between apoE gene polymorphisms and gallstone. Methods We included all the published studies on the association between apoE gene polymorphisms and gall-stone. A meta-analysis was employed to summarize all these studies, calculate the pooled OR and its 95% confidence interval (95% CI) , and test the overall effects. The Egger's publication bias analysis and sensitivity analysis were carried out to evaluate the reliability and stability of the meta-analysis. Results Eleven association studies between the apoE gene polymorphisms and gallstone fulfilled our inclusion criteria. There were 1248 patients with gallstones and 1660 controls. Remarkable heterogeneities were discovered in the allele ε4 and genotype E3/E4 of apoE between gallstone and control subjects in these studies (P<0. 05). Their ORs and 95%CIs were 1.32 (1.01, 1. 71), 1. 60 (1. 04, 2. 46), respectively (P<0. 05). The results of sensitivity analysis and publication bias analysis showed the reliability and stability of this meta-analysis. Conclusion apoE gene polymorphisms are associated with gallstone. Those with the alleleε4 or genotype E3 /E4 had a higher risk of suffering from gallstone.
5.MicroRNA-491-5p is involved in the pathogenesis of degenerative lumbar scoliosis by targeting matrix metalloproteinase 9
Lei WANG ; Tianwang LI ; Jianqiang LIU ; Xiaozong LIU ; Zhaoguo WANG ; Yan TIAN ; Yongxing ZHANG ; Wei WANG
Chinese Journal of Tissue Engineering Research 2016;(2):248-253
BACKGROUND:MicroRNAs are widely involved in the regulation of protein expression, and play a critical role in many physiological and pathological processes in the body. But microRNA expression profile in degenerative lumbar scoliosis is rarely reported and understood. OBJECTIVE:To compare the microRNA expression profile in the normal intervertebral disc and degenerative lumbar scoliosis and to identify degenerative lumbar scoliosis-specific microRNAs, folowed by functional validation. METHODS: Total RNA samples were extracted from the nucleus pulposus tissues of 57 patients with degenerative lumbar scoliosis as experimental groups and the normal nucleus pulposus tissues of 42 patients with lumbar fractures as control group. An initial screening of differentialy expressed microRNAs in the nucleus pulposus tissues by microRNA microarray was performed in 10 samples from each group. Subsequently, differentialy expressed microRNAs were validated using real-time quantitative RCR. The level of differentialy expressed microRNAs in the degenerative nucleus pulposus tissues was investigated. Then, the functional analysis of microRNAs in regulating colagen II expression was carried out. Western blot and luciferase reporter assay were also used to detect target genes. RESULTS AND CONCLUSION:We identified 22 microRNAs that were differentialy expressed (17 upregulated and 5 downregulated) in degenerative lumbar scoliosis patients compared with the controls. Folowing real-time quantitative RCR confirmation, miR-491-5p was significantly down-regulated in degenerative nucleus pulposus tissues in comparison with the controls. Moreover, its level was closely correlated with the pathological grading of disc degeneration. Overexpression of miR-491-5p promoted type II colagen expression in nucleus pulposus cels. Bioinformatics target prediction identified matrix metaloproteinase-9 as a putative target of miR-491-5p. Furthermore, luciferase reporter assays demonstrated that miR-491-5p directly targeted matrix metaloproteinase-9 and affected its protein expression in nucleus pulposus cels. These results show that the downregulation of miR-491-5p induces type II colagen loss by directly targeting matrix metaloproteinase-9, thereby resulting in degeneration of the intervertebral disc and degenerative lumbar scoliosis. This study also underscores the potential of miR-491-5p as a novel therapeutic target in degenerative lumbar scoliosis.
6.Downregulated Hsa-let-7f contributes to the loss of type II collagen by targeting interleukin-10/STAT3 signaling pathway in degenerative lumbar scoliosis
Lei WANG ; Tianwang LI ; Jianqiang LIU ; Xiaozong LIU ; Zhaoguo WANG ; Yan TIAN ; Yongxing ZHANG ; Wei WANG
Chinese Journal of Tissue Engineering Research 2016;20(15):2225-2232
BACKGROUND:MicroRNAs (miRNAs) play an important role in a variety of diseases. Investigation of miRNA expression profile in degenerative lumbar scoliosis is beneficial for understanding its pathogenesis, providing a novel therapeutic target. Therefore, we tested the hypothesis that miRNAs promote intervertebral disc degeneration through the interleukin-10/STAT3 signaling pathway, a potential regulator of intervertebral disc degeneration.
OBJECTIVE:To compare the differentialy expressed miRNAs in the intervertebral disc tissues from patients with degenerative lumbar scoliosis and normal controls and to identify specific miRNAs in degenerative lumbar scoliosis folowed by functional validation.
METHODS: An initial screening of miRNA expression in nucleus pulposus tissues by miRNA Solexa Sequencing was performed in samples from 10 patients with degenerative lumbar scoliosis and 10 controls, respectively. Subsequently, differentialy expressed miRNAs were validated using qRT-PCR. The level of differentialy expressed miRNAs in degenerative nucleus pulposus tissues was investigated. Then, functional analysis of the miRNAs in regulating type II colagen expression was carried out. Western blot and luciferase reporter assay were used to further confirm the target gene.
RESULTS AND CONCLUSION: We identified 30 miRNAs that were differentialy expressed (16 upregulated and 14 downregulated) in patients with degenerative lumbar scoliosis compared with controls. Folowing qRT-PCR confirmation, Has-let-7f was significantly down-regulated in degenerative nucleus pulposus tissues as compared with controls. Moreover, its level was correlated with the severity of disc degeneration. Overexpression of Has-let-7f promoted type II colagen expression in nucleus pulposus cels. Knockout of interleukin-10 induced effects on nucleus pulposus cels similar to Has-let-7f. Bioinformatics target prediction identified interleukin-10 as a putative target of Has-let-7f. Furthermore, luciferase reporter assays demonstrated that Has-let-7f altered the expression of STAT3 and matrix metaloproteinase-2. These findings indicate that the downregulation of Has-let-7f induces type II colagen loss by directly targeting inleukin-10, thereby resulting in intervertebral disc degeneration and degenerative lumbar scoliosis. Has-let-7f is likely to be a novel therapeutic target for degenerative lumbar scoliosis.
7.Role of ADAM8 in tumor metastasis
Qi JIA ; Zhaoguo LIU ; Suyun YU ; Lichuan CHEN ; Pingting ZHU ; Wenxing CHEN ; Aiyun WANG ; Yin LU
Chinese Pharmacological Bulletin 2017;33(8):1037-1040
Tumor metastasis is one of the important biological characteristics of malignant tumor,which is closely related with the prognosis of the cancer patients.High expression of ADAM8 in varieties of tumors was revealed in many recent studies,and such aberrant expression played a crucial role in regulating of tumor metastasis.Studies showed that overexpression of ADAM8 attenuated the intercellular adhesion effect,promoted tumor angiogenesis,and enhanced the degradation of ECM as well as the releasing of cytokines.Therefore,suppression of ADAM8 may lead to inhibition of tumor metastasis,which makes ADAM8 a particular attractive target as it can be used as a prognostic indicator and a potential therapeutic target of malignant tumor.A review about the relations between ADAM8 protein′s abnormal expression and tumor occurrence was discussed in this paper,also include discussion about the mechanisms of ADAM8 protein′s disorder-induced tumor formation,as well as therapeutic strategies based on ADAM8-targeted,which may provide references for follow-up research and clinical treatment.
8.Research progress of a new oncotherapy target TRAP1
Peiliang SHEN ; Zhaoguo LIU ; Lihua SUN ; Xu WANG ; Ying SHEN ; Hongyan WU ; Aiyun WANG ; Yin LU
Chinese Pharmacological Bulletin 2016;32(4):459-462,463
Tumor necrosis factor receptor-associated protein 1 (TRAP1),as one of the main members of the heat shock protein 90 family, resists oxidative stress-induced apoptosis as well as predominantly maintains the integrity of mitochondria and cellu-lar homeostasis. Abnormal expression of TRAP1 was herein closely related to the onset and progression of a wide variety of tumors. As a key regulatory factor mediating energy metabolism within tumor cells, TRAP1 may be able to kill them by interfer-ing with such metabolism. More importantly, the abnormal ex-pression of TRAP1 played a less important role in normal cells, allowing TRAP1 to be a particularly attractive target as it can be used in tumor treatment or interference. The relationship be-tween abnormal expression of TRAP1 protein and tumor onset was reviewed. Besides, the mechanism by which disordered TRAP1 protein expression induced tumor formation was postula-ted, which may provide references for future research and clini-cal treatment.
9.Research progress of salvianolic acid B in cardiovascular diseases
Chao LIN ; Zhaoguo LIU ; Xing QIAN ; Yuan YAO ; Bin XU ; Huimin BIAN
Chinese Pharmacological Bulletin 2015;(4):449-451,452
Cardiovascular disease is a serious threat to human health and quality of life ,and it has become the leading cause of death in human.Thus,looking for effective drugs to reduce the mortality and morbidity of such a disease has become a problem to be solved.Due to its good efficacy of activating blood circula-tion and dissipating blood stasis,salvia miltiorrhiza has been widely used in the treatment of cardiovascular disease and ob-tained a good curative effect.Salvianolic acid B is one of the main water-soluble components of salvia miltiorrhiza extract and studies have shown that salvianolic acid B possesses many biolog-ical activities,which not only has a good protective effect on my-ocardial infarction,but could significantly alleviate myocardial ischemia-reperfusion injury.This article reviews the research progress of salvianolic acid B in cardiovascular diseases,and al-so includes discussion about the mechanisms of salvianolic acid B in the regulation of cardiovascular diseases,which may provide references for follow-up research and clinical treatment.
10.Research progress on the role of autophagy in cardiovascular diseases
Chao LIN ; Zhaoguo LIU ; Xing QIAN ; Bin XU ; Dongqiao BAO ; Yu LI ; Huimin BIAN
Chinese Pharmacological Bulletin 2014;(10):1347-1349
Autophagy is a common phenomenon which widely ex-ists in eukaryotic cells. Researches have shown that autophagy plays a critical role in maintaining cellular hemostasis, cell com-ponents update and keeping a normal physiological state. In re-cent years, the study has found that autophagy is closely related to the growth, the development of cardiovascular diseases and tumors. Further studies show that in different pathological condi-tions, autophagy could both promote angiogenesis and inhibit the formation of blood vessels. Therefore, it is particularly critical to elucidate the mechanisms of autophagy in the regulation of angio-genesis in different pathological conditions. The role of autophagy in cardiovascular diseases especially in the regulation of angio-genesis is discussed in this paper. Besides, the paper also in-cludes the discussion about the mechanisms of autophagy in the regulation angiogenesis, which may provide references for follow-up research and clinical treatment.