1.Osteopontin Promoter Polymorphism at Locus-156 is Associated with HCC in Patients with HBV Infection in Chinese Population
Hong SHI ; Yuankai WU ; Guoli LIN ; Xiangyong LI
Journal of Sun Yat-sen University(Medical Sciences) 2017;38(5):717-721
[Objective]To study the association between the polymorphisms in the promoter region of Osteopontin(OPN)with hepatitis B virus(HBV)-related HCC.[Methods]A total of 225 cases diagnosed with hepatitis B virus(HBV)-related HCC and 200 age-matched patients with HBV infection without HCC were collected. Three polymorphisms(-156delG/G,-443T/C and-616T/G)in the Osteopontin promoter were genotyped using direct sequencing.[Results]The frequency of-156delG/delG genotype in the HCC group was higher than that of in the control group (P = 0.003). There was a significantly increased frequency of the allele-156delG(P<0.001)in HCC patients. Logistic regression analysis was performed to show an increase HCC risk associated with the delG variant genotype(OR1.64;95%CI 1.25~2.16). There were no differences between the groups in the genotype distributions and allele frequencies of SNP-443T/C and-616T/G.[Conclusion]Our findings suggest that allele-156delG in the Osteopontin promoter may be a marker for risk of HCC with HBV infection in Chinese Han population.
2.Analysis of Effectiveness of Deep Brain Stimulation for Forty Cases of Parkinson's Disease
Guoli SHI ; Mingrui ZHOU ; Jiachu ZHANG ; Ninghui ZHAO ; Boming SUN
Journal of Kunming Medical University 2016;37(9):113-115
Objective To investigate the effectiveness of deep brain stimulation (DBS) treating Parkinson's disease.Methods Forty cases of Parkinson's disease were selected from March 2014 to August 2015.The clinical symptoms of these patients were described and quantitatively analyzed with Unified Parkinson's Disease Rating Scale (UPDRS) before and after the procedure of DBS surgery.Results After deep brain stimulation surgery,the symptoms including muscle stiffness,static tremor,bradykinesia were improved,UPDRS scores were significantly lower and the demanding dosage of Parkinson disease drugs such as L-dopa/benserazide and L-dopa/carbidopa were also reduced.Conclusion Deep brain stimulation for Parkinson's disease is safe and effective.It can obviously control the symptoms,reduce the dosage of oral drugs,and improve the quality of life.
3.PDX-1 transfected human adipose-derived mesenchymal stem cells:differentiation into islet-like cells and treatment of type 1 diabetes via cell transplantation
Guangjun SHI ; Guoli BAI ; Xueying TAN ; Jijun ZHU ; Ping XU
Chinese Journal of Tissue Engineering Research 2017;21(13):2062-2067
BACKGROUND:Recent studies have shown that adipose-derivedmesenchymal stem cells (ADMSCs) not only have multilineage differentiation potential, but also exert an important role in blood sugar balance and hormone production.OBJECTIVE:To observe the differentiation potential of human ADMSCs (hADMSCs) into functional islet-like cells and the therapeutic effect of hADMSCs transplantation in diabetic rats.METHODS:PDX-1 gene was transfected into hADMSCs by adenovirus. Cell differentiation and insulin secretion were identified and detected by dithizone staining and ELISA, respectively. Twenty male Sprague-Dawley rats were randomly divided into control group (n=4), diabetes group (n=8) and transplantation group (n=8). Rats in the latter two groups were subjected to making diabetic models by 65 mg/kg streptozotocin injection. Afterwards, rats in the transplantation group were given PDX-1 transfected ADMSCs via the tail vein.RESULTS AND CONCLUSION:At 15 days after transfection, the number of insulin positive cells and insulin secretion were both increased significantly (P < 0.05). Fasting glucose levels in the transplantation group decreased significantly (P < 0.05), while the body weight increased significantly (P < 0.05). In the diabetic group, the fasting glucose level still maintained at a high level, and the body weight of rats was significantly decreased. These results implicated that PDX-1 gene could induce hADMSCs differentiating into functional islet-like cells. PDX-1 transfected ADMSCs transplantation is effective in treating diabetic rats, but the mechanism needs further study.
4.The study on pathological changes of tau protein in the APP/tau/PS1 triple transgenic Alzheimer's disease mice
Zhonghao ZHANG ; Qingxue SHI ; Lei WEN ; Ming YING ; Ao WANG ; Guoli SONG
Chinese Journal of Geriatrics 2014;33(6):657-660
Objective To identify the genotype of the APP/tau/PS1 triple transgenic Alzheimer's disease (AD) mice,and investigate the pathological changes of tau protein in the pathogenic process.Methods Using specific primers of PS1,APP,tau gene,the genotypes of the triple transgenic AD mice were identified.Expression of tau protein in hippocampal tissue of mouse model aged 2,4,8 month was detected by immunohistochemistry.The expression of tau and its hyperphosphorylation in different sites in the hippocampal tissue and different month old mice was detected by Western blotting.Results PCR amplification fragment of 960 bp,530 bp and 400 bp of transgenic mouse genome were the expected size of APP,PS1,tau,respectively.Expression of tau in hippocampal CA3 region was increased obviously in the 8 month old mice.Compared with the normal wild-type mice,the expressions of tau and phosphorylation of pS262,pS404 and pS202 were increased significantly in hippocampus tissue of the transgenic mice (P<0.01).Expression of tau were significantly higher in 8-and 12-monthsold mice than in 2 months-old mice (P < 0.01).Phosphorylation level of pS404 and Ps202 was significantly increased since 2-months-old in transgenic mouse compared to the wild type mouse (P<0.01),and in 8-monthold mice,there was also a significant increase as compared to that in 2 month-old mice (P<0.01).As to the phosphorylation level of pSs262,the significant increase did not appear until 12 months old in transgenic mouse as compared to the wild type mouse (P<0.01).Conclusions The triple transgenic mice can stably express the APP/tau/PS1 gene.The transgenic animals can be a useful model with the pathological features of tau of AD.The phosphorylation level of tau in different site increases in different time,which will provide useful research reference in Alzheimer's disease pathology and medication research.
5.miR-10b overexpressionpromotes the proliferation of lung cancer cell line A549
Jing TANG ; Zhongquan SHI ; Ling HU ; Guoli LI ; Xiaoling FENG ; Feng LIU
Basic & Clinical Medicine 2017;37(8):1108-1112
Objective To explore the of miR-10b cordribution in patients with non-small cell lung cancer (NSCLC) and adjacent tissues,and to investigate the effect of miR-10b on the malignant change of lung cancer cell A549 by regulating the expression of Kruppel-like factor 4 (KLF4).Methods Fourty patients with NSCLC were selected with lung cancer and in miR-10b expression adjacent tissues of lung cancer cell A549 transfected miR-10b mimics,changes of CCK-8 assay were used to detect the proliferation of lung cancer cells;real time PCR and Western blot were used to examine the cell KLF4 mRNA and protein levels;soft agar colony formation assay was used to detect the expression of miR-10b on the proliferation of lung cancer cell A549 tumor malignant.Results miR-10b expression in lung cancer A549 cells and lung cancer tissue were higher than that of normal lung epithelial 16HBE cells and cancer adjacent tissues;overexpression of miR-10banalogue in A549 cells,KLF4 protein levels significantly decreased,KLF4 mRNA was not changed significantly;miR-10b expression significantly increased the growth of A549 cells.Conclusions The distribution of miR-10b in different cell types and tissues may be different,which may promote the proliferation and malignancy of lung cancer cells by inhibitingthe expression of KLF4.
6.Estimation of postmortem interval by determination of K~+ concentration in aqueous humor
Guoli LV ; Yaping ZHOU ; Zhigang LI ; Xinshu XU ; Licong YU ; Xin WANG ; He SHI ; Chuanchao XU
Chinese Journal of Forensic Medicine 2010;25(1):24-26
Objective To investigate the applicability of the K~+ concentration in aqueous humor to estimate postmortem interval(PMI).Methods 30 White New-Zealand rabbit were sacrificed by air embolism and divided into 10 groups.Aqueous humor and vitreous humor were sampled at 0.5h,1h,3h,6h,8h,12h,16h,20h,and 24h after death.The concentration of potassium,sodium and calcium were analyzed by an autoanalyzer and the data were statistically processed by SPSS software for Windows.Results Increase in potassiam concentration in aqueous humor was correlated with the postmortem interval(R~2=0.956).Conclusion Measurement of potassium concentration in aqueous humor may be used for PMI estimation.
7.11'-Deoxyverticillin A induces caspase-dependent cell apoptosis in PC3M cells.
Yingdi SHI ; Yingqiu ZHANG ; Yangxiao NI ; Guoli SHI ; Huaiyi YANG
Chinese Journal of Biotechnology 2012;28(1):96-103
Recent years, the incidence and mortality of prostate cancer have increased dramatically in China. At earlier stages, most diagnosed prostate cancers are responsive to androgen depletion treatment, yet, nearly all patients will eventually progress to metastatic androgen-independent prostate cancer (AIPC), which still has no effective therapeutic method or drug to deal with. 11'-Deoxyverticillin A (C42) belongs to the family of epipolythiodioxopiperazines (ETPs), an interesting class of fungal toxins that inhibit farnesyl transferase. Compounds holding such a property have been explored as putative anticancer agents. In this study, using PC3M cells, an AIPC cell line, we investigated the effect of the compound on apoptosis and explored the underlying mechanism. It revealed that C42 markedly enhanced the activity of caspase-3/7 and increased the accumulation of the cleaved PARP, all of which are the markers of apoptosis. It also revealed that C42 either decreased cell viability or inhibited the growth of PC3M cells. Moreover, we observed that the loss of cell viability and cell growth inhibition induced by C42 were both time- and dosage dependent. Taken together, we indicated that C42 can induce caspase-dependent apoptosis in AIPC cells, and the results presented here will broaden our knowledge about the molecular mechanisms by which C42 exerts its anticancer activity, and future work in this direction may provide valuable information in the development of these compounds into effective cancer therapeutic strategies against androgen-independent prostate cancer.
Apoptosis
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drug effects
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Caspase 3
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metabolism
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Caspase 7
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metabolism
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Cell Line, Tumor
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Disulfides
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pharmacology
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Farnesyltranstransferase
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antagonists & inhibitors
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Humans
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Male
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Mycotoxins
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pharmacology
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Piperazines
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pharmacology
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Prostatic Neoplasms
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pathology
8.Transcription factor p53 inhibits dengue virus infection through typeⅠinterferon signaling pathway
Guoli LI ; Junlei ZHANG ; Yanling HU ; Houliang SUN ; Zhongquan SHI ; Xiaoshan LI ; Jia LIU ; Xiancai RAO ; Fuquan HU
Chinese Journal of Microbiology and Immunology 2014;(4):278-281
Objective To investigate the role of a transcription factor p 53 in dengue virus infec-tion.Methods A plasmid expressing siRNA specific for p 53 gene was constructed and then used to prepare HepG2 cell line with a suppressed expression of p 53 protein.The expression of p53 protein was detected by Western blot assay .A wild type control group and a siRNA group were set up by infecting wildtype HepG 2 cells and p53 low expressing HepG2 cells with type 2 dengue viruses,respectively.The virus titers in two dif-ferent cells were determined by plaque forming assay using Vero cells .Indirect immunofluorescence assay was performed to detect virus multiplication .The apoptosis of virus infected cells were analyzed by flow cytome-try.ELISA was performed to analyze the levels of IFN-βsecreted by infected cells from two groups .Results Compared with wildtype control group ,the cells in siRNA group showed a suppressed expression of p 53 pro-tein,suggesting that the HepG2 cell line with low p53 protein expression was successfully established .The vi-rus titer in supernatants of the cells from siRNA group was about 100-fold higher than that of wildtype control group at 24 hours after viral infection .Fluorescence activated cell sorting analysis showed that the numbers of green fluorescence labeled cells were remarkably increased in siRNA group .We speculated that p53 protein might play a role in the inhibition of dengue virus infection as indicated by the observed results .The numbers of apoptotic cells showed no significant difference between two groups .However,the level of IFN-βsecreted by wildtype HepG2 cells was six times higher than that of the cells in siRNA group .Conclusion p53 pro-tein might inhibit dengue virus infection through the activation of type Ⅰ interferon signaling pathway rather than enhance cell apoptosis .
9.Efficacy of 48-week tenofovir disoproxil fumarate therapy in patients who were unresponsive to nucleoside-analogue treatments.
Mingxing HUANG ; Xinhua LI ; Yuankai WU ; Ling TAO ; Yusheng JIE ; Xiangyong LI ; Hong SHI ; Guoli LIN ; Fangji YANG ; Yunlong AO ; Yihua PANG ; Min ZHANG ; Yutian CHONG
Chinese Journal of Hepatology 2014;22(4):266-271
OBJECTIVETo evaluate the efficacy and safety of tenofovir disoproxil fumarate (TDF) in patients with chronic hepatitis B (CHB) after failure of nucleoside-analogues (NAs).
METHODSA total of 30 CHB patients who had been previously treated with NAs and had subsequently completed a 48-week course of TDF were retrospectively investigated. Patients' data of HBV DNA level (log10 copies/ml) and rate of undetectable HBV DNA at treatment weeks 0 (baseline), 4, 12, 24, 36 and 48 were collected for evaluation. The lower limit of HBV DNA detection was 100 IU/ml. The serum alanine aminotransferase (ALT) normalization rate, hepatitis B e antigen (HBeAg) seroconversion rate, viral breakthrough (VBT) rate, viral response (VR) rate, and adverse events were determined upon treatment completion. Statistical analyses were carried out using the Student's t-test, the x² test or the Kaplan-Meier method.
RESULTSOver the 48-week treatment period, HBV DNA levels declined significantly from baseline (week 4:(2.11 ± 0.38) log10 IU/ml, t =5.582; week 12:(0.93 ± 0.31) log10 IU/ ml, t =9.303; week 24:(0.75 ± 0.20) log10 IU/ml, t =3.123; week 36:(0.16 ± 0.19) log10 IU/ml, t =10.759; week 48:(0.14 ± 0.25) log10 IU/ml, t =12.202) (all P less than 0.01). However, the rates of HBV DNA reduction and of cumulative reduction were comparable at weeks 24, 36 and 48 (all P more than 0.05). The most robust decline in HBV DNA levels was observed at week 4 ((2.11 ± 0.38) log10 IU/ml) and the highest cumulative HBV DNA reduction was observed at week 24 ((3.79 ± 0.37) log10 IU/ml). The rate of undetectable HBV DNA at week 4 (26.7%) was significantly lower than that at weeks 24 (87.5%, P less than 0.01), 36 (80.0%, P=0.007), and 48 (88.9%, P=0.001). The median time to achieving undetectable HBV DNA was 10.4 weeks (range:3.43-34.0 weeks). At week 48, the rates of VR, HBeAg seroconversion, and VBT were 88.9% ,6.7%, and 0% respectively. During treatment, the levels of creatine kinase were more than two times the upper limit normal in 9.2% of the patients, and were comparable at each time point examined (all P more than 0.05). All patients showed a normal level of serum creatinine throughout the treatment period.
CONCLUSIONFor CHB patients with non-response to NAs, TDF can suppress HBV DNA replication very quickly and achieve a high rate of ALT normalization with a low rate of adverse events.
Adenine ; administration & dosage ; analogs & derivatives ; therapeutic use ; Adult ; Antiviral Agents ; administration & dosage ; therapeutic use ; DNA, Viral ; blood ; Female ; Hepatitis B e Antigens ; blood ; Hepatitis B, Chronic ; drug therapy ; Humans ; Male ; Middle Aged ; Organophosphonates ; administration & dosage ; therapeutic use ; Retrospective Studies ; Tenofovir ; Young Adult
10.Preventive and therapeutic effects of Bateri-7 on radiation-induced intestinal injury in mice
Guoli LIU ; Xiujun SONG ; Yemei WANG ; Zuyin YU ; Xing SHEN ; Lei SHI ; Hua JIN ; Xinru WANG
Chinese Journal of Radiological Medicine and Protection 2022;42(11):839-844
Objective:To study the protective effect of Mongolian medicine Bateri-7 on radiation-induced intestinal injury in mice.Methods:C57BL/6J male mice were randomly divided into control group, irradiation group and irradiation plus drug administration group, with 10 or 15 mice in each group. For irradiation group, the mice were given a single dose of 12 Gy 60Co γ-rays with total body irradiation. For drug treatment, the mice were gavaged with Bateri-7 (530 mg/kg) 7 d before irradiation until 3 d after IR. At 6 h and 24 h after irradiation, the Tunel positive cells in intestine were detected immunohistochemically. At 3.5 d after irradiation, the structure of intestinal villi was observed by HE staining, and the BrdU and Ki67 positive cells were detected immunohistochemically. The expression levels of IL-6, TNF-α and Cxcl-5 were detected by qPCR. The FITC-dextran in peripheral blood was also determined. Results:The survival of irradiated mice was significantly increased by Bateri-7 ( χ2= 5.84, P < 0.05), but there was no significant difference in weight between two groups ( P > 0.05). The villi length of small intestine in the irradiation plus drug group was significantly longer than that in the irradiation group ( t = 20.24, P < 0.05), and there was no significant difference in the depth of intestinal crypt between two groups ( P > 0.05). At 6 and 24 h after irradiation, the number of Tunel positive cells in intestinal crypts in the irradiation plus drug group was significantly reduced in comparison with the irradiation group ( t = 3.52, 2.90, P < 0.05). At 3.5 d after irradiation, the level of FITC-dextran in serum and the expressions of IL-6, TNF-α and Cxcl-5 in small intestine of mice in the irradiation plus drug group were significantly lower than those in the irradiation group, respectively( t = 6.92, 7.01, 7.18, 13.16, P < 0.05). The number of BrdU and Ki67 positive cells in the crypt of mice in the irradiation plus drug group was higher than that of the irradiation group ( t = 3.91, 2.57, P < 0.05). Conclusions:Mongolian medicine Bateri-7 can effectively alleviate irradiation-induced intestinal injury of mice, which may have a good preventive and therapeutic effect on radiation enteritis.