yanfei xin - Independent Researcher (original) (raw)
Papers by yanfei xin
The effect of different molecular PEG-g-PLG on the resistance of complex to the digestion of DNase I at N/P ratio of 2 and the PLG to DNA charge ratio of 1
1. marker, 2. DNA, 3. PEG-g-PLG, 4. PEG-g-PLG and 5. PEG-g-PLG.<b>Copyright information:<... more 1. marker, 2. DNA, 3. PEG-g-PLG, 4. PEG-g-PLG and 5. PEG-g-PLG.<b>Copyright information:</b>Taken from "A convenient and adjustable surface-modified complex containing poly-L-glutamic acid conjugates as a vector for gene delivery"International Journal of Nanomedicine 2008;3(2):249-256.Published online Jan 2008PMCID:PMC2527664.© 2008 Sun et al, publisher and licensee Dove Medical Press Ltd.
Nitrogen/oxygen dual-doped hierarchical porous carbons with inverse opal-like structure for high performance supercapacitors
Journal of Alloys and Compounds, 2021
Pharmaceutical Biology, 2020
Context: Shenmai Injection (SMI) is usually used to treat atherosclerotic coronary heart disease ... more Context: Shenmai Injection (SMI) is usually used to treat atherosclerotic coronary heart disease and viral myocarditis in China. However, the effect of SMI on multidrug resistance has not been reported. Objective: To investigate the reversal effect of SMI in adriamycin (ADR) resistant breast cancer cell line (MCF-7/ADR) and explore the related molecular mechanisms. Materials and methods: The effect of SMI (0.25, 0.5, 1 mg/mL) to reverse chemoresistance in MCF-7/ADR cells was elucidated by MTT, HPLC-FLD, DAPI staining, flow cytometric analysis, western blotting. At the same time, in vivo test was conducted to probe into the effect of SMI on reversing ADR resistance, and verapamil (10 lM) was used as a positive control. Results: The results showed that the toxicity of ADR to MCF-7/ADR cells was strengthened significantly after treated with SMI (0.25, 0.5, 1 mg/mL), the IC 50 of ADR was decreased 54.4-fold. The intracellular concentrations of ADR were increased 2.2-fold (p < 0.05) and ADR accumulation was enhanced in the nuclei (p < 0.05). SMI could strongly enhance the ADR-induced apoptosis and increase intracellular rhodamine 123 accumulation in MCF-7/ADR cells. Additionally, a combination of ADR and SMI (5 mg/kg) could dramatically reduce the weight and volume of tumour (p < 0.05). Furthermore, the results revealed that SMI might reverse MDR via inhibiting ADR-induced activation of the mitogen-activated protein kinase/nuclear factor (NF)-jB pathway to down-regulated the expression of P-glycoprotein (P-gp). Discussion and conclusions: SMI could potentially be used to treat ADR-resistance. This suggests possibilities for future clinical research.
Life Sciences, 2020
Aims: Doxorubicin (DOX) is an effective anthracycline anticancer drug. However, the clinical usag... more Aims: Doxorubicin (DOX) is an effective anthracycline anticancer drug. However, the clinical usage of it is limited due to its severe cardiotoxicity side effects. Metformin (Met) is a kind of first-line antihyperglycemic drug which has a potential protective effect on the heart,it is often used for oral treatment of type 2 diabetes. In this study, we explored whether Met could attenuate cardiotoxicity induced by DOX. Materials and methods: For the sake of exploring the Met protective effect and mechanism, we established the DOX-induced cardiotoxicity models both in H9C2 cells incubated with 5 μM DOX in vitro and Sprague-Dawley rats treated with 20 mg/kg cumulative dose of DOX. Key findings: Met is able to inhibit growth inhibition and apoptosis of H9C2 cells induced by DOX. The heart indexes of rats were examined to evaluate the Met cardiotoxicity protection. Met improved the abnormal indexes, serum markers of cardiac heart injury, echocardiography, electrocardiogram, cardiac pathology, cardiomyocyte apoptosis, and oxidative stress markers induced by DOX. Furthermore, in vivo and in vitro studies demonstrated that Met protected against DOX-induced increasing cleaved caspase-3 and Bax. Met also prevented the downregulation of Bcl-2, activated the AMPK pathway, and inhibited the MAPK pathway. Significance: Met showed protective effects on DOX-induced cardiotoxicity by reducing oxidative stress and apoptosis, as well as regulating AMPK and MAPK signaling pathways.
Journal of Ginseng Research, 2018
Background: Ginsenosides have been widely used clinically for many years and were regarded as ver... more Background: Ginsenosides have been widely used clinically for many years and were regarded as very safe. However, a few researches on the toxicities of these kinds of agents showed that some ginsenosides may have side-effect on the rats or dogs. So it is extremely necessary to further clarify the potential toxicity of ginsenosides. This study was carried out to investigate long-term toxicity and genotoxicity of 25-methoxydammarane-3, 12, 20-triol (25-OCH 3-PPD), a new derivative of ginsenoside, in beagle dogs. Methods: Twenty-four beagle dogs were divided randomly into four treatment groups and repeatedly orally administered with 25-OCH 3-PPD capsule at 60, 120, and 240 mg/kg/day for 91 consecutive days. Ames, micronucleus, and chromosomal aberration tests were established to analyze the possible genotoxicity of 25-OCH 3-PPD. Results: There was no 25-OCH 3-PPDeinduced systemic toxicity in beagle dogs at any doses. The level of 25-OCH 3-PPD at which no adverse effects were observed was found to be 240 mg/kg/day. The result of Ames test showed that there was no significant increase in the number of revertant colonies of 25-OCH 3-PPD administrated groups compared to the vehicle control group. There were also no significant differences between 25-OCH 3-PPD administrated groups at all dose levels and negative group in the micronucleus test and chromosomal aberration assay. Conclusion: The highest dose level of 25-OCH 3-PPD at which no adverse effects were observed was found to be 240 mg/kg per day, and it is not a genotoxic agent either in somatic cells or germs cells. 25-OCH 3-PPD is an extremely safe candidate compound for antitumor treatment.
Regulatory Toxicology and Pharmacology, 2019
To investigate the possibility of tedizolid phosphate's application in the treatment of intracran... more To investigate the possibility of tedizolid phosphate's application in the treatment of intracranial infection, a preclinical comparative pharmacokinetic study was designed. Based on the assumption that the classic efflux transporters P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) may participate in the transportation of TDZ, two groups of rats were intravenously administered 6 mg/kg tedizolid phosphate alone or 6 mg/kg tedizolid phosphate combined with 1 mg/kg elacridar which was an inhibitor of P-gp and BCRP. Plasma and cerebrospinal fluid samples were collected according to a pharmacokinetic schedule. All the plasma and cerebrospinal fluid samples were assessed with a validated LC-MS/MS method. The penetration ratio of tedizolid from the blood to cerebrospinal fluid was calculated, and a comparison of the penetration ratios between the two groups was made. The mean C max of tedizolid in the CSF in the tedizolid phosphate group and the tedizolid phosphate combined with elacridar group was 154 ng/mL and 300 ng/mL, respectively, and the mean penetration ratio of tedizolid in the tedizolid phosphate group and the tedizolid phosphate combined with elacridar group was 2.16% and 3.53%, respectively. The relatively high C max in the CSF proved the possibility of tedizolid phosphate's application in the treatment of intracranial infection, and the higher penetration ratios, C max, csf and AUC csf of the rats in co-administered elacridar group than those in the single-administration group indicated that the transporters P-gp and BCRP might be involved in the transportation of tedizolid.
Oxidative medicine and cellular longevity, 2017
Fermented papaya extracts (FPEs) are obtained by fermentation of papaya by Aspergillus oryzae and... more Fermented papaya extracts (FPEs) are obtained by fermentation of papaya by Aspergillus oryzae and yeasts. In this study, we investigated the protective effects of FPEs on mammary gland hyperplasia induced by estrogen and progestogen. Rats were randomly divided into 6 groups, including a control group, an FPE-alone group, a model group, and three FPE treatment groups (each receiving 30, 15, or 5 ml/kg FPEs). Severe mammary gland hyperplasia was induced upon estradiol benzoate and progestin administration. FPEs could improve the pathological features of the animal model and reduce estrogen levels in the serum. Analysis of oxidant indices revealed that FPEs could increase superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, decrease malondialdehyde (MDA) level in the mammary glands and serum of the animal models, and decrease the proportion of cells positive for the oxidative DNA damage marker 8-oxo-dG in the mammary glands. Additionally, estradiol benzoate and pr...
International Journal of Nanomedicine, 2008
In order to quantify the amount of ligands or poly(ethylene glycol) (PEG) on each vector, here we... more In order to quantify the amount of ligands or poly(ethylene glycol) (PEG) on each vector, here we developed a system in which poly-L-glutamic acid (PLG) was used as surface modifi cation loading backbone, to which one PEG (MW 5000, 10000, 20000) or epidermal growth factor (EGF) was linked. The PLG conjugates can electro-statically adsorb upon DNA/ polycation complex with positive charge, and, the amount of EGF or PEG on the surface of complexes could be varied. We have made a series of complexes containing the various PLG conjugates and examined their physicochemical properties, and made a comparison of properties and transfection effi ciency between these complexes. EGF-and PEG-modifi ed complexes showed 10-25-folds higher cell transfection effi ciency than unmodifi ed complexes in medium with or without serum.
Human genomics, Jul 25, 2016
Chronic inflammation has been widely considered to be the major risk factor of coronary heart dis... more Chronic inflammation has been widely considered to be the major risk factor of coronary heart disease (CHD). The goal of our study was to explore the possible association with CHD for inflammation-related single nucleotide polymorphisms (SNPs) involved in cytosine-phosphate-guanine (CpG) dinucleotides. A total of 784 CHD patients and 739 non-CHD controls were recruited from Zhejiang Province, China. Using the Sequenom MassARRAY platform, we measured the genotypes of six inflammation-related CpG-SNPs, including IL1B rs16944, IL1R2 rs2071008, PLA2G7 rs9395208, FAM5C rs12732361, CD40 rs1800686, and CD36 rs2065666). Allele and genotype frequencies were compared between CHD and non-CHD individuals using the CLUMP22 software with 10,000 Monte Carlo simulations. Allelic tests showed that PLA2G7 rs9395208 and CD40 rs1800686 were significantly associated with CHD. Moreover, IL1B rs16944, PLA2G7 rs9395208, and CD40 rs1800686 were shown to be associated with CHD under the dominant model. Furth...
Regulatory toxicology and pharmacology : RTP, Jan 18, 2016
Panax notoginseng and its main active ingredients ginsenosides have long been used as medicines a... more Panax notoginseng and its main active ingredients ginsenosides have long been used as medicines and food additives in China. Comparing with the extensive uses and active researches of P. notoginseng and its products, the side effect and probable toxicity were rare. 25-Methoxydammarane-3,12,20-triol (25-OCH3-PPD), a novel dammarane-type triterpene sapogenin that was first isolated from the extract of Panax notoginseng, was proven to have strong antitumor activities against prostate cancer, breast cancer and lung cancer. The aim of the present study was to investigate the potential subchronic toxicity of 25-OCH3-PPD after it was repeatedly orally administered to Sprague-Dawley rats (5/sex/group/each time-point) at dose levels of 0, 150, 300 or 600 mg/kg/day for 13 weeks and 4-week recovery. No mortality and treatment-related toxicity effects were observed as a result of the administration of 25-OCH3-PPD at any dose level (150, 300 and 600 mg/kg) for 92 consecutive days. Although there...
Journal of Shanghai University (English Edition), 2009
The characterization of complexes is particularly critical for quality control and development of... more The characterization of complexes is particularly critical for quality control and development of gene delivery systems. Here, the method of capillary zone electrophoresis (CZE) for the characterization of DNA and poly-L-lysine (MW 28 500) or DNA and poly-L-lysine modified with polyethylene glycol (MW10 000) complexes at various charge ratios in phosphate buffer is described firstly. During the characterization, DNA complexes can be separated into various components with different charge-to-mass ratio, i.e, components with single physicochemical property. And also the size and zeta potential of complexes were characterized by using photon correlation spectroscopy. This method is useful to characterize various complexes formed by DNA and polycations, and has the potential to separate complexes into homogeneous component for better transfection efficiency in vitro and in vivo in future.
PLOS ONE, 2015
Objective Apolipoprotein A5 (APOA5) is associated with plasma triglyceride (TG) levels, a risk fa... more Objective Apolipoprotein A5 (APOA5) is associated with plasma triglyceride (TG) levels, a risk factor for coronary heart disease (CHD). This study explored the association between CHD and the APOA5 rs662799 polymorphism. Methods We collected 1,521 samples (783 CHD patients and 738 controls) for this case-control study. Meta-analysis was performed using Review Manager Software and Stata Software. Results Significant differences were observed between CHD cases and controls at the level of both genotype (χ 2 = 8.964, df = 2, P = 0.011) and allele (χ 2 = 9.180, df = 1, P = 0.002, OR = 1.275, 95% CI = 1.089-1.492). A breakdown analysis by gender showed a significant association of APOA5 rs662799 with CHD in males (χ 2 = 7.770, df = 1, P = 0.005; OR = 1.331, 95% CI = 1.088-1.628). An additional meta-analysis using 21378 cases and 28428 controls established that rs662799 is significantly associated with CHD (P < 0.00001). Conclusion Both our case-control study and meta-analysis confirm a significant association between APOA5 rs662799 and CHD. In addition, our results suggest a male-specific association between the APOA5 rs662799 polymorphism and CHD.
Association of seven thrombotic pathway gene CpG-SNPs with coronary heart disease
Biomedicine & pharmacotherapy = Biomédecine & pharmacothérapie, 2015
Coronary heart disease (CHD) has been considered a thromboembolic arterial diseases. The aim of t... more Coronary heart disease (CHD) has been considered a thromboembolic arterial diseases. The aim of this case-control study was to explore whether the CpG-SNPs of the thrombotic pathway genes contributed to the risk of CHD. A total of 784 CHD patients and 738 healthy controls were recruited in the current association study, which evaluated 7 CpG-SNPs of the thrombotic pathway genes. The CpG-SNPs included THBS4 rs17878919, CYP2C19 rs12773342, P2RY12 rs1491974, ITGA2 rs26680, FGB rs2227389, F7 rs510317 and F5 rs2269648. SNP genotyping was performed with a Sequenom Mass Spectrometry Genetic Analyzer. Our results demonstrated that CYP2C19 rs12773342 polymorphism was significantly associated with CHD in the recessive model (χ(2)=5.41, df=1, P=0.020, OR=1.455, 95% CI=1.060-1.996). A breakdown analysis by age showed that the association of CYP2C19 rs12773342 with CHD was mainly found in individuals aged 55-65 (genotype: χ(2)=7.93, df=2, P=0.019; allele: χ(2)=4.45, df=1, P=0.035). In addition, ...
Scientific reports, Jan 10, 2015
Aberrant DNA methylation can be a potential genetic mechanism in non-small cell lung cancer (NSCL... more Aberrant DNA methylation can be a potential genetic mechanism in non-small cell lung cancer (NSCLC). However, inconsistent findings existed among the recent association studies between cigarette smoking and gene methylation in lung cancer. The purpose of our meta-analysis was to evaluate the role of gene methylation in the smoking behavior of NSCLC patients. A total of 116 genes were obtained from 97 eligible publications in the current meta-analyses. Our results showed that 7 hypermethylated genes (including CDKN2A, RASSF1, MGMT, RARB, DAPK, WIF1 and FHIT) were significantly associated with the smoking behavior in NSCLC patients. The further population-based subgroup meta-analyses showed that the CDKN2A hypermethylation was significantly associated with cigarette smoking in Japanese, Chinese and Americans. In contrast, a significant association of RARB hypermethylation and smoking behavior was only detected in Chinese but not in Japanese. The genes with altered DNA methylation were...
2010 International Conference on Audio, Language and Image Processing, 2010
Digital piano, is an electronic musical instrument for synthesizing traditional piano timbre. Wit... more Digital piano, is an electronic musical instrument for synthesizing traditional piano timbre. With the development of digital signal processing and music synthesis algorithm, the music performance of digital piano is rivaling the traditional piano. This paper use a novel piezoelectric material-Polyvinylidene Fluoride (PVDF) to capture the strength, velocity and duration of keystrokes to substitute the hammer and string of traditional piano. Timbre with different intension, duration is synthesized according to the keystroke information captured by the piezoelectric material.
PLoS ONE, 2013
The goal of our study is to investigate the contribution of promoter DNA methylation of a-adducin... more The goal of our study is to investigate the contribution of promoter DNA methylation of a-adducin (ADD1) gene to the risk of essential hypertension (EH). Using the bisulphite pyrosequencing technology, DNA methylation levels of five CpG dinucleotides on ADD1 promoter were measured among 33 EH cases and 28 healthy controls. Significantly higher ADD1 DNA methylation levels were observed in the females than in the males (CpG1: P = 0.016; CpG2-5: P = 0.021). A breakdown analysis by gender showed that lower CpG1 methylation was associated with an increased risk of EH in females (adjusted P = 0.042). A much more significant association between lower CpG2-5 methylation levels and the increased risk of EH was found in males (adjusted P = 0.008). CpG1 methylation was inversely correlated with age in females (r = 20.407, P = 0.019) but not in males. ADD1 CpG1 and CpG2-5 methylation levels were significantly lower in post-menopausal (.50 years) women than pre-menopausal (#50 years) women (CpG1: P = 0.006; CpG2-5: P = 0.034). A significant interaction between CpG1 methylation and age was found in females (CpG1*age: P = 0.029). CpG2-5 methylation was shown as a significant predictor of EH in males [area under curve (AUC) = 0.855, P = 0.001], in contrast that CpG1 methylation was a trend toward indicator in females (AUC = 0.699, P = 0.054). In addition, significant differences were observed between males and females for alanine aminotransferase (ALT, P = 0.001), aspartate aminotransferase (AST, P = 0.005) and uric acid (P,0.001). The concentration of AST was inversely correlated with ADD1 CpG2-5 methylation levels in female controls (r = 20.644, P = 0.024). These observations may bring new hints to elaborate the pathogenesis of EH.
Experimental and Toxicologic Pathology, 2012
N(G)-nitro-d-arginine (d-NNA) could convert into N(G)-nitro-l-arginine (l-NNA) in vivo, and kidne... more N(G)-nitro-d-arginine (d-NNA) could convert into N(G)-nitro-l-arginine (l-NNA) in vivo, and kidney is the major target organ. In the chiral inversion process, a number of reactive oxygen species (ROS) were generated and NOS activity was inhibited, which may cause renal damage. Salvia miltiorrhiza (SM), a traditional Chinese drug, was used in the treatment of cardiovascular diseases and chronic renal failure. The aim of the present study was to investigate the kidney damage caused by d-NNA administration for 12 weeks and to evaluate the effects of treatment with SM on d-NNA-induced kidney damage. The rats, induced with d-NNA for period of 12 weeks, showed significant elevation of Blood Urea Nitrogen (BUN), Creatinine (Crea) and MDA levels, and significant decrease of SOD and GSH-Px activities, as compared with control group. In addition, the kidney of rats induced with d-NNA only showed remarkable histopathology, including severe mononuclear cell infiltration, mild tubular dilatation and congestion, and moderate interstitial desmoplasia. After 4 weeks SM treatment, the activity of SOD, GSH-Px and iNOS and the production of NO were significantly higher (P < 0.05), and the levels of BUN, Crea and MDA were significantly lower than that of d-NNA only group (P < 0.05). In addition, treatment with SM showed histopathological protection in tubular dilatation, congestion, mononuclear cell infiltration and interstitial desmoplasia. The present results indicate that the toxicity of d-NNA relates to its ability to generate oxidative stress and upregulate NOS activity in rat kidney. SM probably ameliorates d-NNA-induced nephrotoxicity in rats according to scavenging free radical and upregulating NOS activity.
Chmp1A acts as a tumor suppressor gene that inhibits proliferation of renal cell carcinoma
Cancer Letters, 2012
Renal cell carcinoma (RCC) is a highly malignant and often fatal disease of the kidney. Chmp1A is... more Renal cell carcinoma (RCC) is a highly malignant and often fatal disease of the kidney. Chmp1A is a member of the Endosomal Sorting Complex Required for Transport (ESCRT-III) family, and plays a role in the cytoplasm in sorting proteins to the multivesicular body (MVB). Chmp1A functions as a tumor suppressor gene and has been reported in pancreatic tumor cells. Here, we examined the expression level of Chmp1A in human RCC tissues and renal tumor cells by real-time quantitative RT-PCR and western blot. We found that the expression level of Chmp1A is significantly lower in RCC tissues and renal tumor cells compared with adjacent non-tumorous tissues and normal renal cells. Additionally, inhibition of Chmp1A expression by shRNA induced tumor formation in normal renal cells. However, inhibition of Chmp1A did not significantly affect tumor cell proliferation in vitro and tumor progression in vivo. Interestingly, overexpression of Chmp1A using a eukaryotic plasmid inhibited the proliferation of renal tumor cells in vitro and the growth of renal tumor in vivo. Thus, our results demonstrate that Chmp1A functions as a tumor suppressor gene in renal cells and may be a useful target for treatment of RCC.
The effect of different molecular PEG-g-PLG on the resistance of complex to the digestion of DNase I at N/P ratio of 2 and the PLG to DNA charge ratio of 1
1. marker, 2. DNA, 3. PEG-g-PLG, 4. PEG-g-PLG and 5. PEG-g-PLG.<b>Copyright information:<... more 1. marker, 2. DNA, 3. PEG-g-PLG, 4. PEG-g-PLG and 5. PEG-g-PLG.<b>Copyright information:</b>Taken from "A convenient and adjustable surface-modified complex containing poly-L-glutamic acid conjugates as a vector for gene delivery"International Journal of Nanomedicine 2008;3(2):249-256.Published online Jan 2008PMCID:PMC2527664.© 2008 Sun et al, publisher and licensee Dove Medical Press Ltd.
Nitrogen/oxygen dual-doped hierarchical porous carbons with inverse opal-like structure for high performance supercapacitors
Journal of Alloys and Compounds, 2021
Pharmaceutical Biology, 2020
Context: Shenmai Injection (SMI) is usually used to treat atherosclerotic coronary heart disease ... more Context: Shenmai Injection (SMI) is usually used to treat atherosclerotic coronary heart disease and viral myocarditis in China. However, the effect of SMI on multidrug resistance has not been reported. Objective: To investigate the reversal effect of SMI in adriamycin (ADR) resistant breast cancer cell line (MCF-7/ADR) and explore the related molecular mechanisms. Materials and methods: The effect of SMI (0.25, 0.5, 1 mg/mL) to reverse chemoresistance in MCF-7/ADR cells was elucidated by MTT, HPLC-FLD, DAPI staining, flow cytometric analysis, western blotting. At the same time, in vivo test was conducted to probe into the effect of SMI on reversing ADR resistance, and verapamil (10 lM) was used as a positive control. Results: The results showed that the toxicity of ADR to MCF-7/ADR cells was strengthened significantly after treated with SMI (0.25, 0.5, 1 mg/mL), the IC 50 of ADR was decreased 54.4-fold. The intracellular concentrations of ADR were increased 2.2-fold (p < 0.05) and ADR accumulation was enhanced in the nuclei (p < 0.05). SMI could strongly enhance the ADR-induced apoptosis and increase intracellular rhodamine 123 accumulation in MCF-7/ADR cells. Additionally, a combination of ADR and SMI (5 mg/kg) could dramatically reduce the weight and volume of tumour (p < 0.05). Furthermore, the results revealed that SMI might reverse MDR via inhibiting ADR-induced activation of the mitogen-activated protein kinase/nuclear factor (NF)-jB pathway to down-regulated the expression of P-glycoprotein (P-gp). Discussion and conclusions: SMI could potentially be used to treat ADR-resistance. This suggests possibilities for future clinical research.
Life Sciences, 2020
Aims: Doxorubicin (DOX) is an effective anthracycline anticancer drug. However, the clinical usag... more Aims: Doxorubicin (DOX) is an effective anthracycline anticancer drug. However, the clinical usage of it is limited due to its severe cardiotoxicity side effects. Metformin (Met) is a kind of first-line antihyperglycemic drug which has a potential protective effect on the heart,it is often used for oral treatment of type 2 diabetes. In this study, we explored whether Met could attenuate cardiotoxicity induced by DOX. Materials and methods: For the sake of exploring the Met protective effect and mechanism, we established the DOX-induced cardiotoxicity models both in H9C2 cells incubated with 5 μM DOX in vitro and Sprague-Dawley rats treated with 20 mg/kg cumulative dose of DOX. Key findings: Met is able to inhibit growth inhibition and apoptosis of H9C2 cells induced by DOX. The heart indexes of rats were examined to evaluate the Met cardiotoxicity protection. Met improved the abnormal indexes, serum markers of cardiac heart injury, echocardiography, electrocardiogram, cardiac pathology, cardiomyocyte apoptosis, and oxidative stress markers induced by DOX. Furthermore, in vivo and in vitro studies demonstrated that Met protected against DOX-induced increasing cleaved caspase-3 and Bax. Met also prevented the downregulation of Bcl-2, activated the AMPK pathway, and inhibited the MAPK pathway. Significance: Met showed protective effects on DOX-induced cardiotoxicity by reducing oxidative stress and apoptosis, as well as regulating AMPK and MAPK signaling pathways.
Journal of Ginseng Research, 2018
Background: Ginsenosides have been widely used clinically for many years and were regarded as ver... more Background: Ginsenosides have been widely used clinically for many years and were regarded as very safe. However, a few researches on the toxicities of these kinds of agents showed that some ginsenosides may have side-effect on the rats or dogs. So it is extremely necessary to further clarify the potential toxicity of ginsenosides. This study was carried out to investigate long-term toxicity and genotoxicity of 25-methoxydammarane-3, 12, 20-triol (25-OCH 3-PPD), a new derivative of ginsenoside, in beagle dogs. Methods: Twenty-four beagle dogs were divided randomly into four treatment groups and repeatedly orally administered with 25-OCH 3-PPD capsule at 60, 120, and 240 mg/kg/day for 91 consecutive days. Ames, micronucleus, and chromosomal aberration tests were established to analyze the possible genotoxicity of 25-OCH 3-PPD. Results: There was no 25-OCH 3-PPDeinduced systemic toxicity in beagle dogs at any doses. The level of 25-OCH 3-PPD at which no adverse effects were observed was found to be 240 mg/kg/day. The result of Ames test showed that there was no significant increase in the number of revertant colonies of 25-OCH 3-PPD administrated groups compared to the vehicle control group. There were also no significant differences between 25-OCH 3-PPD administrated groups at all dose levels and negative group in the micronucleus test and chromosomal aberration assay. Conclusion: The highest dose level of 25-OCH 3-PPD at which no adverse effects were observed was found to be 240 mg/kg per day, and it is not a genotoxic agent either in somatic cells or germs cells. 25-OCH 3-PPD is an extremely safe candidate compound for antitumor treatment.
Regulatory Toxicology and Pharmacology, 2019
To investigate the possibility of tedizolid phosphate's application in the treatment of intracran... more To investigate the possibility of tedizolid phosphate's application in the treatment of intracranial infection, a preclinical comparative pharmacokinetic study was designed. Based on the assumption that the classic efflux transporters P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) may participate in the transportation of TDZ, two groups of rats were intravenously administered 6 mg/kg tedizolid phosphate alone or 6 mg/kg tedizolid phosphate combined with 1 mg/kg elacridar which was an inhibitor of P-gp and BCRP. Plasma and cerebrospinal fluid samples were collected according to a pharmacokinetic schedule. All the plasma and cerebrospinal fluid samples were assessed with a validated LC-MS/MS method. The penetration ratio of tedizolid from the blood to cerebrospinal fluid was calculated, and a comparison of the penetration ratios between the two groups was made. The mean C max of tedizolid in the CSF in the tedizolid phosphate group and the tedizolid phosphate combined with elacridar group was 154 ng/mL and 300 ng/mL, respectively, and the mean penetration ratio of tedizolid in the tedizolid phosphate group and the tedizolid phosphate combined with elacridar group was 2.16% and 3.53%, respectively. The relatively high C max in the CSF proved the possibility of tedizolid phosphate's application in the treatment of intracranial infection, and the higher penetration ratios, C max, csf and AUC csf of the rats in co-administered elacridar group than those in the single-administration group indicated that the transporters P-gp and BCRP might be involved in the transportation of tedizolid.
Oxidative medicine and cellular longevity, 2017
Fermented papaya extracts (FPEs) are obtained by fermentation of papaya by Aspergillus oryzae and... more Fermented papaya extracts (FPEs) are obtained by fermentation of papaya by Aspergillus oryzae and yeasts. In this study, we investigated the protective effects of FPEs on mammary gland hyperplasia induced by estrogen and progestogen. Rats were randomly divided into 6 groups, including a control group, an FPE-alone group, a model group, and three FPE treatment groups (each receiving 30, 15, or 5 ml/kg FPEs). Severe mammary gland hyperplasia was induced upon estradiol benzoate and progestin administration. FPEs could improve the pathological features of the animal model and reduce estrogen levels in the serum. Analysis of oxidant indices revealed that FPEs could increase superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, decrease malondialdehyde (MDA) level in the mammary glands and serum of the animal models, and decrease the proportion of cells positive for the oxidative DNA damage marker 8-oxo-dG in the mammary glands. Additionally, estradiol benzoate and pr...
International Journal of Nanomedicine, 2008
In order to quantify the amount of ligands or poly(ethylene glycol) (PEG) on each vector, here we... more In order to quantify the amount of ligands or poly(ethylene glycol) (PEG) on each vector, here we developed a system in which poly-L-glutamic acid (PLG) was used as surface modifi cation loading backbone, to which one PEG (MW 5000, 10000, 20000) or epidermal growth factor (EGF) was linked. The PLG conjugates can electro-statically adsorb upon DNA/ polycation complex with positive charge, and, the amount of EGF or PEG on the surface of complexes could be varied. We have made a series of complexes containing the various PLG conjugates and examined their physicochemical properties, and made a comparison of properties and transfection effi ciency between these complexes. EGF-and PEG-modifi ed complexes showed 10-25-folds higher cell transfection effi ciency than unmodifi ed complexes in medium with or without serum.
Human genomics, Jul 25, 2016
Chronic inflammation has been widely considered to be the major risk factor of coronary heart dis... more Chronic inflammation has been widely considered to be the major risk factor of coronary heart disease (CHD). The goal of our study was to explore the possible association with CHD for inflammation-related single nucleotide polymorphisms (SNPs) involved in cytosine-phosphate-guanine (CpG) dinucleotides. A total of 784 CHD patients and 739 non-CHD controls were recruited from Zhejiang Province, China. Using the Sequenom MassARRAY platform, we measured the genotypes of six inflammation-related CpG-SNPs, including IL1B rs16944, IL1R2 rs2071008, PLA2G7 rs9395208, FAM5C rs12732361, CD40 rs1800686, and CD36 rs2065666). Allele and genotype frequencies were compared between CHD and non-CHD individuals using the CLUMP22 software with 10,000 Monte Carlo simulations. Allelic tests showed that PLA2G7 rs9395208 and CD40 rs1800686 were significantly associated with CHD. Moreover, IL1B rs16944, PLA2G7 rs9395208, and CD40 rs1800686 were shown to be associated with CHD under the dominant model. Furth...
Regulatory toxicology and pharmacology : RTP, Jan 18, 2016
Panax notoginseng and its main active ingredients ginsenosides have long been used as medicines a... more Panax notoginseng and its main active ingredients ginsenosides have long been used as medicines and food additives in China. Comparing with the extensive uses and active researches of P. notoginseng and its products, the side effect and probable toxicity were rare. 25-Methoxydammarane-3,12,20-triol (25-OCH3-PPD), a novel dammarane-type triterpene sapogenin that was first isolated from the extract of Panax notoginseng, was proven to have strong antitumor activities against prostate cancer, breast cancer and lung cancer. The aim of the present study was to investigate the potential subchronic toxicity of 25-OCH3-PPD after it was repeatedly orally administered to Sprague-Dawley rats (5/sex/group/each time-point) at dose levels of 0, 150, 300 or 600 mg/kg/day for 13 weeks and 4-week recovery. No mortality and treatment-related toxicity effects were observed as a result of the administration of 25-OCH3-PPD at any dose level (150, 300 and 600 mg/kg) for 92 consecutive days. Although there...
Journal of Shanghai University (English Edition), 2009
The characterization of complexes is particularly critical for quality control and development of... more The characterization of complexes is particularly critical for quality control and development of gene delivery systems. Here, the method of capillary zone electrophoresis (CZE) for the characterization of DNA and poly-L-lysine (MW 28 500) or DNA and poly-L-lysine modified with polyethylene glycol (MW10 000) complexes at various charge ratios in phosphate buffer is described firstly. During the characterization, DNA complexes can be separated into various components with different charge-to-mass ratio, i.e, components with single physicochemical property. And also the size and zeta potential of complexes were characterized by using photon correlation spectroscopy. This method is useful to characterize various complexes formed by DNA and polycations, and has the potential to separate complexes into homogeneous component for better transfection efficiency in vitro and in vivo in future.
PLOS ONE, 2015
Objective Apolipoprotein A5 (APOA5) is associated with plasma triglyceride (TG) levels, a risk fa... more Objective Apolipoprotein A5 (APOA5) is associated with plasma triglyceride (TG) levels, a risk factor for coronary heart disease (CHD). This study explored the association between CHD and the APOA5 rs662799 polymorphism. Methods We collected 1,521 samples (783 CHD patients and 738 controls) for this case-control study. Meta-analysis was performed using Review Manager Software and Stata Software. Results Significant differences were observed between CHD cases and controls at the level of both genotype (χ 2 = 8.964, df = 2, P = 0.011) and allele (χ 2 = 9.180, df = 1, P = 0.002, OR = 1.275, 95% CI = 1.089-1.492). A breakdown analysis by gender showed a significant association of APOA5 rs662799 with CHD in males (χ 2 = 7.770, df = 1, P = 0.005; OR = 1.331, 95% CI = 1.088-1.628). An additional meta-analysis using 21378 cases and 28428 controls established that rs662799 is significantly associated with CHD (P < 0.00001). Conclusion Both our case-control study and meta-analysis confirm a significant association between APOA5 rs662799 and CHD. In addition, our results suggest a male-specific association between the APOA5 rs662799 polymorphism and CHD.
Association of seven thrombotic pathway gene CpG-SNPs with coronary heart disease
Biomedicine & pharmacotherapy = Biomédecine & pharmacothérapie, 2015
Coronary heart disease (CHD) has been considered a thromboembolic arterial diseases. The aim of t... more Coronary heart disease (CHD) has been considered a thromboembolic arterial diseases. The aim of this case-control study was to explore whether the CpG-SNPs of the thrombotic pathway genes contributed to the risk of CHD. A total of 784 CHD patients and 738 healthy controls were recruited in the current association study, which evaluated 7 CpG-SNPs of the thrombotic pathway genes. The CpG-SNPs included THBS4 rs17878919, CYP2C19 rs12773342, P2RY12 rs1491974, ITGA2 rs26680, FGB rs2227389, F7 rs510317 and F5 rs2269648. SNP genotyping was performed with a Sequenom Mass Spectrometry Genetic Analyzer. Our results demonstrated that CYP2C19 rs12773342 polymorphism was significantly associated with CHD in the recessive model (χ(2)=5.41, df=1, P=0.020, OR=1.455, 95% CI=1.060-1.996). A breakdown analysis by age showed that the association of CYP2C19 rs12773342 with CHD was mainly found in individuals aged 55-65 (genotype: χ(2)=7.93, df=2, P=0.019; allele: χ(2)=4.45, df=1, P=0.035). In addition, ...
Scientific reports, Jan 10, 2015
Aberrant DNA methylation can be a potential genetic mechanism in non-small cell lung cancer (NSCL... more Aberrant DNA methylation can be a potential genetic mechanism in non-small cell lung cancer (NSCLC). However, inconsistent findings existed among the recent association studies between cigarette smoking and gene methylation in lung cancer. The purpose of our meta-analysis was to evaluate the role of gene methylation in the smoking behavior of NSCLC patients. A total of 116 genes were obtained from 97 eligible publications in the current meta-analyses. Our results showed that 7 hypermethylated genes (including CDKN2A, RASSF1, MGMT, RARB, DAPK, WIF1 and FHIT) were significantly associated with the smoking behavior in NSCLC patients. The further population-based subgroup meta-analyses showed that the CDKN2A hypermethylation was significantly associated with cigarette smoking in Japanese, Chinese and Americans. In contrast, a significant association of RARB hypermethylation and smoking behavior was only detected in Chinese but not in Japanese. The genes with altered DNA methylation were...
2010 International Conference on Audio, Language and Image Processing, 2010
Digital piano, is an electronic musical instrument for synthesizing traditional piano timbre. Wit... more Digital piano, is an electronic musical instrument for synthesizing traditional piano timbre. With the development of digital signal processing and music synthesis algorithm, the music performance of digital piano is rivaling the traditional piano. This paper use a novel piezoelectric material-Polyvinylidene Fluoride (PVDF) to capture the strength, velocity and duration of keystrokes to substitute the hammer and string of traditional piano. Timbre with different intension, duration is synthesized according to the keystroke information captured by the piezoelectric material.
PLoS ONE, 2013
The goal of our study is to investigate the contribution of promoter DNA methylation of a-adducin... more The goal of our study is to investigate the contribution of promoter DNA methylation of a-adducin (ADD1) gene to the risk of essential hypertension (EH). Using the bisulphite pyrosequencing technology, DNA methylation levels of five CpG dinucleotides on ADD1 promoter were measured among 33 EH cases and 28 healthy controls. Significantly higher ADD1 DNA methylation levels were observed in the females than in the males (CpG1: P = 0.016; CpG2-5: P = 0.021). A breakdown analysis by gender showed that lower CpG1 methylation was associated with an increased risk of EH in females (adjusted P = 0.042). A much more significant association between lower CpG2-5 methylation levels and the increased risk of EH was found in males (adjusted P = 0.008). CpG1 methylation was inversely correlated with age in females (r = 20.407, P = 0.019) but not in males. ADD1 CpG1 and CpG2-5 methylation levels were significantly lower in post-menopausal (.50 years) women than pre-menopausal (#50 years) women (CpG1: P = 0.006; CpG2-5: P = 0.034). A significant interaction between CpG1 methylation and age was found in females (CpG1*age: P = 0.029). CpG2-5 methylation was shown as a significant predictor of EH in males [area under curve (AUC) = 0.855, P = 0.001], in contrast that CpG1 methylation was a trend toward indicator in females (AUC = 0.699, P = 0.054). In addition, significant differences were observed between males and females for alanine aminotransferase (ALT, P = 0.001), aspartate aminotransferase (AST, P = 0.005) and uric acid (P,0.001). The concentration of AST was inversely correlated with ADD1 CpG2-5 methylation levels in female controls (r = 20.644, P = 0.024). These observations may bring new hints to elaborate the pathogenesis of EH.
Experimental and Toxicologic Pathology, 2012
N(G)-nitro-d-arginine (d-NNA) could convert into N(G)-nitro-l-arginine (l-NNA) in vivo, and kidne... more N(G)-nitro-d-arginine (d-NNA) could convert into N(G)-nitro-l-arginine (l-NNA) in vivo, and kidney is the major target organ. In the chiral inversion process, a number of reactive oxygen species (ROS) were generated and NOS activity was inhibited, which may cause renal damage. Salvia miltiorrhiza (SM), a traditional Chinese drug, was used in the treatment of cardiovascular diseases and chronic renal failure. The aim of the present study was to investigate the kidney damage caused by d-NNA administration for 12 weeks and to evaluate the effects of treatment with SM on d-NNA-induced kidney damage. The rats, induced with d-NNA for period of 12 weeks, showed significant elevation of Blood Urea Nitrogen (BUN), Creatinine (Crea) and MDA levels, and significant decrease of SOD and GSH-Px activities, as compared with control group. In addition, the kidney of rats induced with d-NNA only showed remarkable histopathology, including severe mononuclear cell infiltration, mild tubular dilatation and congestion, and moderate interstitial desmoplasia. After 4 weeks SM treatment, the activity of SOD, GSH-Px and iNOS and the production of NO were significantly higher (P < 0.05), and the levels of BUN, Crea and MDA were significantly lower than that of d-NNA only group (P < 0.05). In addition, treatment with SM showed histopathological protection in tubular dilatation, congestion, mononuclear cell infiltration and interstitial desmoplasia. The present results indicate that the toxicity of d-NNA relates to its ability to generate oxidative stress and upregulate NOS activity in rat kidney. SM probably ameliorates d-NNA-induced nephrotoxicity in rats according to scavenging free radical and upregulating NOS activity.
Chmp1A acts as a tumor suppressor gene that inhibits proliferation of renal cell carcinoma
Cancer Letters, 2012
Renal cell carcinoma (RCC) is a highly malignant and often fatal disease of the kidney. Chmp1A is... more Renal cell carcinoma (RCC) is a highly malignant and often fatal disease of the kidney. Chmp1A is a member of the Endosomal Sorting Complex Required for Transport (ESCRT-III) family, and plays a role in the cytoplasm in sorting proteins to the multivesicular body (MVB). Chmp1A functions as a tumor suppressor gene and has been reported in pancreatic tumor cells. Here, we examined the expression level of Chmp1A in human RCC tissues and renal tumor cells by real-time quantitative RT-PCR and western blot. We found that the expression level of Chmp1A is significantly lower in RCC tissues and renal tumor cells compared with adjacent non-tumorous tissues and normal renal cells. Additionally, inhibition of Chmp1A expression by shRNA induced tumor formation in normal renal cells. However, inhibition of Chmp1A did not significantly affect tumor cell proliferation in vitro and tumor progression in vivo. Interestingly, overexpression of Chmp1A using a eukaryotic plasmid inhibited the proliferation of renal tumor cells in vitro and the growth of renal tumor in vivo. Thus, our results demonstrate that Chmp1A functions as a tumor suppressor gene in renal cells and may be a useful target for treatment of RCC.