Publications by authors named "Wan-Li Li"

27 Publications

  • Page 1 of 1

Biomineralization of Cd and inhibition on rhizobacterial Cd mobilization function by Bacillus Cereus to improve safety of maize grains.

Chemosphere 2021 Jun 10;283:131095. Epub 2021 Jun 10.

Guangdong Key Laboratory of Environmental Pollution and Health, School of Environment, Jinan University, Guangzhou, 510632, China. Electronic address:

Reducing cadmium (Cd) bioavailability and rhizobacterial Cd mobilization functions in the rhizosphere via the inoculation of screened microbial inoculum is an environmental-friendly strategy to improve safety of crop grains. In this study, Bacillus Cereus, a model Cd resistant strain, was selected to explore its effects on Cd bioavailability and uptake, bacterial metabolic functions related to Cd mobilization. Results indicated that inoculation of Bacillus Cereus in maize roots of sand pot with water-soluble Cd (0.06-0.15 mg/kg) and soil pot with high Cd-contaminated soil (total Cd: 2.33 mg/kg; Cd extracted by NHNO: 38.6 μg/kg) could decrease water-soluble Cd ion concentration by 7.7-30.1% and Cd extracted with NHNO solution by 7.8-22.5%, inducing Cd concentrations in maize grains reduced by 10.6-39.9% and 17.4-38.6%, respectively. Even for a single inoculation in soil, Cd concentration in maize grains still satisfy food safety requirements (Cd content: 0.1 mg/kg dry weight) due to its successful colonization on root surface of maize. Bacillus Cereus could enrich more plant growth promotion bacteria (PGPB) and down-regulate the expression of genes related to bacterial motility, membrane transports, carbon and nitrogen metabolism in the rhizosphere soil, decreasing Cd bioavailability in soil. Approximately 80% Cd in media was transferred into intracellular, meanwhile Cd salts (sulfide and/or phosphate) were produced in Bacillus Cereus through biomineralization process. Overall, this study could provide a feasible method for improving safety of maize grains via the inoculation of Bacillus Cereus under Cd pollution.
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http://dx.doi.org/10.1016/j.chemosphere.2021.131095DOI Listing
June 2021

Nitrogen fertilizer affects rhizosphere Cd re-mobilization by mediating gene AmALM2 and AmALMT7 expression in edible amaranth roots.

J Hazard Mater 2021 Jun 6;418:126310. Epub 2021 Jun 6.

Key Laboratory of Environmental Pollution and Health of Guangdong Province, School of Environment, Jinan University, Guangzhou 510632, China. Electronic address:

In-situ stabilization of Cd-contaminated farmland is a commonly used remediation technology. Yet, rhizosphere metabolites (e.g., organic acids) during crop cultivation may cause Cd re-mobilization and over-accumulation. Here, we identified four pivotal cytomembrane-localized genes underlying Cd accumulation difference between two contrasting edible amaranth cultivars based on root gene expression profile, studied their subcellular localization and functional characteristics, and then investigated effects of nitrogen fertilizer on their expression and rhizosphere Cd re-mobilization. Results showed that more Cd accumulated by edible amaranth was due to rhizosphere Cd mobilization by mediating high expression of AmALMT2 and AmALMT7 genes, not Cd transporters in roots. This was confirmed by heterologous expression of AmALMT2 and AmALMT7 genes in Arabidopsis thaliana, since they mediated malic, fumaric, succinic, and aspartic acids efflux. Furthermore, nitrogen influencing rhizosphere acidification might be closely associated with organic acids efflux genes. Compared with N-NO application, N-NH was massively assimilated into glutamates and oxaloacetates through up-regulating glutamine synthetase and alanine-aspartate-glutamate metabolic pathways, thereby enhancing TCA cycle and organic acids efflux dominated by binary carboxylic acids via up-regulating AmALMT2 and AmALMT7 genes, which finally caused Cd re-mobilization. Therefore, N-NO-dominated nitrogen retarded rhizosphere Cd re-mobilization via inhibiting organic acids efflux function of AmALMT2 and AmALMT7 proteins.
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http://dx.doi.org/10.1016/j.jhazmat.2021.126310DOI Listing
June 2021

Nitrogen fertilizer management affects remobilization of the immobilized cadmium in soil and its accumulation in crop tissues.

Environ Sci Pollut Res Int 2021 Jun 20;28(24):31640-31652. Epub 2021 Feb 20.

College of Resources and Environment, Zhongkai University of Agriculture and Engineering, Guangzhou, 510225, China.

Immobilization of soil cadmium (Cd) has been the strategy mostly used in remediation of Cd-contaminated arable soil. However, Cd might be remobilized after the immobilization process through the acid-soluble and complexation effects. Development of agronomic management technologies to prevent soil Cd remobilization after the immobilization process was an important pathway to control the food safety of agricultural products in soils with the immobilized Cd. In this study, the ammonia (NH-N) and nitrate (NO-N) forms with concentrations of 60, 90, and 150 mg-N kg soil were performed for evaluating their effects on Cd remobilization with planted or unplanted treatments and Cd accumulation in tissues of edible amaranth (Liuye). With an initial soil palygorskite-bound fraction Cd concentration of 0.6 mg kg, bioavailable Cd in rhizosphere soils and Cd in crop shoots respectively increased from 11.4 to 20.6 μg kg (dry soil weight) and 6.92 to 14.92 mg kg (dry plant weight) in planted NH-N treatments, while significantly lower concentrations of bioavailable Cd in rhizosphere soils and Cd in crop tissues were observed with planted NO-N treatments. Compared with that of planted NO-N treatments, decreasing pH value (i.e., 7.64 to 7.18) induced by root proton efflux during the absorption of NH-N, enhancive organic/amino acid (oxalic acid, lactic acid, L-proline, and so on) secretion from roots, and increasing abundance of bacteria distributed in phyla Proteobacteria, Cyanobacteria, and Bacteroidetes with Cd mobilization ability in rhizosphere soils were the main reasons found in this study for the higher Cd remobilization in soils and Cd accumulation in crop under NH-N treatments. Moreover, the direct effect of NH-N on remobilization of immobilized Cd by upregulating the expression abundances of genes associated with pyruvate metabolism and amino acids metabolism was more significant than that of NO-N. In summary, the use of NO-N as preferred N fertilizer was more efficient to ensure the food safety of agricultural products than that of NH-N in Cd-contaminated arable soil after immobilization process.
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http://dx.doi.org/10.1007/s11356-021-12868-zDOI Listing
June 2021

Metformin protects high glucose‑cultured cardiomyocytes from oxidative stress by promoting NDUFA13 expression and mitochondrial biogenesis via the AMPK signaling pathway.

Mol Med Rep 2020 Dec 14;22(6):5262-5270. Epub 2020 Oct 14.

Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011, P.R. China.

Tissue damage in diabetes is at least partly due to elevated reactive oxygen species production by the mitochondrial respiratory chain during hyperglycemia. Sustained hyperglycemia results in mitochondrial dysfunction and the abnormal expression of mitochondrial genes, such as NADH: Ubiquinone oxidoreductase subunit A13 (NDUFA13). Metformin, an AMP‑activated protein kinase (AMPK) activator, protects cardiomyocytes from oxidative stress by improving mitochondrial function; however, the exact underlying mechanisms are not completely understood. The aim of the present study was to investigated the molecular changes and related regulatory mechanisms in the response of H9C2 cardiomyocytes to metformin under high glucose conditions. H9C2 cells were subjected to CCK‑8 assay to assess cell viability. Reactive oxygen species generation was measured with DCFH‑DA assay. Western blotting was used to analyze the expression levels of NDUFA13, AMPK, p‑AMPK and GAPDH. Reverse transcription‑quantitative PCR was used to evaluate the expression levels of mitochondrial genes and transcription factors. It was observed that metformin protected H9C2 cardiomyocytes by suppressing high glucose (HG)‑induced elevated oxidative stress. In addition, metformin stimulated mitochondrial biogenesis, as indicated by increased expression levels of mitochondrial genes (NDUFA1, NDUFA2, NDUFA13 and manganese superoxide dismutase) and mitochondrial biogenesis‑related transcription factors [peroxisome proliferator‑activated receptor‑gamma coactivator‑1α, nuclear respiratory factor (NRF)‑1, and NRF‑2] in the metformin + HG group compared with the HG group. Moreover, metformin promoted mitochondrial NDUFA13 protein expression via the AMPK signaling pathway, which was abolished by pretreatment with the AMPK inhibitor, Compound C. The results suggested that metformin protected cardiomyocytes against HG‑induced oxidative stress via a mechanism involving AMPK, NDUFA13 and mitochondrial biogenesis.
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http://dx.doi.org/10.3892/mmr.2020.11599DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646981PMC
December 2020

Improving cadmium mobilization by phosphate-solubilizing bacteria via regulating organic acids metabolism with potassium.

Chemosphere 2020 Apr 25;244:125475. Epub 2019 Nov 25.

Guangdong Key Laboratory of Environmental Pollution and Health, School of Environment, Jinan University, Guangzhou, 510632, China. Electronic address:

Organic acids secreted by phosphorus-solubilizing bacteria (PSB) is one of the main biological metabolites with cadmium (Cd) mobilization capacity in the conversion of insoluble precipitate forms to bioavailable forms in contaminated soil. However, the fluctuating concentrations of nutrient elements caused by agricultural activities may result in the substantial variances of carbohydrate metabolism of microorganisms involved in Cd remediation, it is therefore essential to study how metabolic strategies, especially for organic acids, affected by the environmentally friendly fertilizers, such as potassium (K). In this study, adding K (KCl) concentrations from 0.0 to 100.0 mg/L in medium clearly accelerated Cd mobilization from 15.9 to 35.9 mg/L via inducing the secretion of tartaric acid, 3-hydroxybutyrate, fumaric and succinic acids, increased by 10.0-, 7.5-, 4.3- and 4.1-fold changes, respectively. Current data revealed that the significant differences of metabolic pathways and genes expressions with the varied K concentrations included: ⅰ) K induces a substantial up-regulation in metabolic pathway of pyruvic acid to oxaloacetate and tartaric acids; ⅱ) the varied expression of genes involved in encoding enzymes of tricarboxylic acid cycle result in the up-regulated fumaric acid, succinic acid and 3-hydroxybutyrate; ⅲ) the expression of genes related enzyme cysteine and glutamate metabolism processes promoted with the increasing bioavailable Cd concentrations. Besides, P-type ATPase activity increased with K levels, indicating that H efflux and medium acidification were strengthened. In general, an appropriate enhancement of K based fertilizer is an effective manner for soil Cd remediation via the regulation of organic acids metabolism and H secretion of PSB.
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http://dx.doi.org/10.1016/j.chemosphere.2019.125475DOI Listing
April 2020

[Clinical Significance of CRLF2 High Expression in Bone Marrow Mononuclear Cells from Children with Acute Lymphoblastic Leukemia].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2019 Aug;27(4):1058-1063

Department of Hematology, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China,E-mail:

Objective: To detect the expression of CRLF2 in bone marrow mononuclear cells from children with newly diagnosed acute lymphoblastic leukemia(ALL) and to explore its clinical significance in pediatric ALL.

Methods: A total of 218 children with newly diagnosed ALL who achieveal the complete remission and had the complete follow-up information were selected, and the expression level of CRLF2 in bone marrow mononuclear cells of these children was detected by real-time fluorescent quantitative PCR, and the significance of CRLF2 expression level in clinical prognosis of ALL children was analyzed by using statistical method.

Results: 28 cases in 218 children with complete data showed high expression of CRLF2. The cumulative recurrence rate in the CRLF2 high expression group was significantly higher than that in the low expression group (53.6% vs 12.6%) (P<0.01). The predicted 5-year recurrence-free survival rate (RFS) of ALL children with CRLF2 high expression was significantly higher than that of low expression group (P<0.01). There was no significant difference in the predicted 5-year RFS between ALL children with CRLF2 low and high expression in the standard-risk(SR) group (P>0.05). The predicted 5-year RFS of ALL children with CRLF2 low expression was higher than that of ALL children with CRLF2 high expression in the intermediate-risk (IR) and high-risk (HR) groups. (P<0.05). Cox analysis showed that CRLF2 high expression is an independent risk factor for the relapse of children with ALL.

Conclusion: The recurrence rate of pediatric ALL with CRLF2 high expression is high, and CRLF2 high expression is an important prognostic factor for high risk of relapse in ALL children with IR and HR. It is necessary to use CRLF2 expression as an indicator of risk stratification in pediatric ALL.
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http://dx.doi.org/10.19746/j.cnki.issn.1009-2137.2019.04.011DOI Listing
August 2019

[Study on 4 weeks medium intensity aeraobic exercise induce the difference expression of the proteomics in rat atrial muscle].

Zhongguo Ying Yong Sheng Li Xue Za Zhi 2018 May;34(5):450-456 463

Department of Basic Medicine, Changsha Medical University, Changsha 410219, China.

Objective: To investigate the effect of moderate-intensity aerobic exercise on the differential expression of rat atrial muscle Proteomics and genes, which provide research basis for the rehabilitation of chronic cardiovascular diseases and exercise -induced cardiac remodeling research.

Methods: Twenty male SD rats were randomly divided into control group and experimental group (=10) according to body weight. Rats in the experimental group were trained (6 days per week),which lasted for 4 weeks of moderate-intensity aerobic exercise at a rate of 24 m·min for 40 min (load intensity equivalent to 60%~70% VO). The proteins were separated by two dimensional gel electrophoresis, and the tandem time-of- flight mass spectrometer technique was used to identify 13 candidate target protein spots. The expression levels of these 13 protein spots were up-regulated more than 5 times or down -regulated to below 1/5. The mRNA of six target proteins were detected by reverse transcription-polymerase chain reaction (RT-PCR).

Results: By software analysis, the experimental group compared with the control group, there were 8 protein points which their expression reduced more than 4/5 and 5 protein points up-regulated more than 5 times, 13 proteins were identified by mass spectrometry protein spots, the final identification results acquired 8 proteins and a unknown protein of molecular mass 54 KDa, such as:pyruvate dehydrogenase E1α1, mitochondrial aconitate hydratase, protein disulfide isomerase A3, methylmalonic acid semialdehyde dehydrogenase, mitochondrial dihydrolipoic acid dehydrogenase, isovaleryl coenzyme A dehydrogenase, glutathione synthetase, mitogen-activated protein kinase 3 and so on. Compared with the control group, the mRNA expression of methylmalonic acid semialdehyde dehydrogenase in the atrial muscle of rats was decreased after 4 weeks of moderate aerobic exercise (<0.05), the mRNA expression levels of mitochondria Ⅱ lipoic acid dehydrogenase, protein disulfide isomerase A3, mitochondrial aconitate hydratase and glutathione synthetase were decreased (>0.05); The mRNA expression level of isopentenyl-CoA dehydrogenase was increased (>0.05). The results indicated that the mRNA expression level was not completely consistent with the changes in mass spectrometry identification results.

Conclusions: The 4 weeks moderate-intensity aerobic exercise induced ignificant changes of rats atrial muscle protemics. The majority of the 13 identified target proteins in this experiment are energy metabolism enzymes. The majority of the expression of the target protein and the mRNA expression in the atrial muscle is inconsistent and different. Exercise may affect the regulation of gene transcription or downstream translation and modification of these target proteins, resulting in the change of differential expression.
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http://dx.doi.org/10.12047/j.cjap.5683.2018.102DOI Listing
May 2018

[Effects of minimal residual disease level on day 33 of remission induction and IKZF1 genotype on the survival of children with B-lineage acute lymphoblastic leukemia].

Zhongguo Dang Dai Er Ke Za Zhi 2018 Jul;20(7):538-542

Department of Hematology, Hunan Children's Hospital, Changsha 410007, China.

Objective: To study the effects of minimal residual disease (MRD) level on day 33 of remission induction and IKZF1 genotype on the survival of children with B-lineage acute lymphoblastic leukemia (B-ALL).

Methods: A total of 152 children with newly-diagnosed B-ALL who had complete remission after the first cycle of the chemotherapy and had complete follow-up information were enrolled in this study. According to the MRD detection by flow cytometry on day 33 of remission induction, they were divided into three groups: standard-risk (SR) group (MRD <10; n=60), intermediate-risk (IR) group (10≤ MRD <10; n=55), and high-risk (HR) group (MRD ≥10; n=37). Nested RT-PCR was used to determine the IKZF1 genotype of all children before chemotherapy. The effects of MRD level on day 33 of remission induction and IKZF1 genotype on the recurrence-free survival (RFS) of children with B-ALL were analyzed.

Results: There were 7 common IKZF1 subtypes in all the 152 children with B-ALL: IK1, IK2/3, IK4, IK6, IK8, IK9, and IK10. Of the 152 children, 130 had functional subtypes of IKZF1 and 22 had non-functional subtypes of IKZF1. During the follow-up period, relapse occurred in 26 (17%) children, and the recurrence rate was highest in the HR group (P<0.05). However, there was no significant difference in the recurrence rate between the SR group and the IR group (P>0.05). The cumulative recurrence rate of the children with non-functional subtypes of IKZF1 was significantly higher than that of those with functional types of IKZF1 (P<0.01). The predicted 5-year RFS rates in the SR, IR, and HR groups were (94.2±2.9)%, (86.7±3.8)%, and (56.2±4.5)% respectively (P<0.05). The 5-year RFS rate of the children with functional subtypes of IKZF1 was significantly higher than that of those with non-functional subtypes of IKZF1 (P<0.01). There was no significant difference in the predicted 5-year RFS rate between the children with functional subtypes of IKZF1 and those with non-functional subtypes of IKZF1 in the SR group (P>0.05). However, the predicted 5-year RFS rate of the children with functional subtypes of IKZF1 was significantly higher than that of those with non-functional subtypes of IKZF1 in the IR group and the HR group (P<0.05).

Conclusions: B-ALL children with non-functional subtypes of IKZF1 have a high recurrence rate, and the recurrence rate will be even higher in B-ALL children with non-functional subtypes of IKZF1 and MRD ≥10 on day 33 of chemotherapy.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7389200PMC
July 2018

Serum and urine metabolomics study reveals a distinct diagnostic model for cancer cachexia.

J Cachexia Sarcopenia Muscle 2018 02 19;9(1):71-85. Epub 2017 Nov 19.

Department of Pharmacy, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.

Background: Cachexia is a multifactorial metabolic syndrome with high morbidity and mortality in patients with advanced cancer. The diagnosis of cancer cachexia depends on objective measures of clinical symptoms and a history of weight loss, which lag behind disease progression and have limited utility for the early diagnosis of cancer cachexia. In this study, we performed a nuclear magnetic resonance-based metabolomics analysis to reveal the metabolic profile of cancer cachexia and establish a diagnostic model.

Methods: Eighty-four cancer cachexia patients, 33 pre-cachectic patients, 105 weight-stable cancer patients, and 74 healthy controls were included in the training and validation sets. Comparative analysis was used to elucidate the distinct metabolites of cancer cachexia, while metabolic pathway analysis was employed to elucidate reprogramming pathways. Random forest, logistic regression, and receiver operating characteristic analyses were used to select and validate the biomarker metabolites and establish a diagnostic model.

Results: Forty-six cancer cachexia patients, 22 pre-cachectic patients, 68 weight-stable cancer patients, and 48 healthy controls were included in the training set, and 38 cancer cachexia patients, 11 pre-cachectic patients, 37 weight-stable cancer patients, and 26 healthy controls were included in the validation set. All four groups were age-matched and sex-matched in the training set. Metabolomics analysis showed a clear separation of the four groups. Overall, 45 metabolites and 18 metabolic pathways were associated with cancer cachexia. Using random forest analysis, 15 of these metabolites were identified as highly discriminating between disease states. Logistic regression and receiver operating characteristic analyses were used to create a distinct diagnostic model with an area under the curve of 0.991 based on three metabolites. The diagnostic equation was Logit(P) = -400.53 - 481.88 × log(Carnosine) -239.02 × log(Leucine) + 383.92 × log(Phenyl acetate), and the result showed 94.64% accuracy in the validation set.

Conclusions: This metabolomics study revealed a distinct metabolic profile of cancer cachexia and established and validated a diagnostic model. This research provided a feasible diagnostic tool for identifying at-risk populations through the detection of serum metabolites.
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http://dx.doi.org/10.1002/jcsm.12246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5803608PMC
February 2018

Scutellarin protects against doxorubicin-induced acute cardiotoxicity and regulates its accumulation in the heart.

Arch Pharm Res 2017 Jul 17;40(7):875-883. Epub 2017 Mar 17.

Department of Pharmacy, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600, Road Yishan, Shanghai, 200233, People's Republic of China.

The clinical use of doxorubicin (DOX) is limited by its dose-dependent cardiotoxicity. The present study investigated the effects of scutellarin against DOX-induced cardiotoxicity in rats using pharmacodynamic and pharmacokinetic approaches. DOX (20 mg/kg) was injected intraperitoneally (i.p.) as a single dose, and scutellarin (5 mg/kg/day) was injected intravenously (i.v.) for 3 days. Rats treated with DOX showed acute cardiotoxicity as indicated by the elevated serum lactate dehydrogenase (LDH) activity (4057.8 ± 107.2 vs. 2032.7 ± 70.95), tissue malondialdehyde (MDA) level (2.083 ± 0.10 vs. 1.103 ± 0.09), cardiac troponin T (cTnT) concentration (0.1695 ± 0.0114 ng/mL), the decreased left ventricular ejection fraction (LVEF) (47.75 ± 15.79 vs. 78.72 ± 7.25) and left ventricular fractional shortening (LVFS) (20.66 ± 8.06 vs. 43.7 ± 6.76) compared with those of the control group. Cotreatment with scutellarin significantly decreased the LDH activity (2595.9 ± 72.73), MDA level (1.380 ± 0.06), cTnT concentration (0.0222 ± 0.0041 ng/m L), increased LVEF (76.70 ± 3.91) and LVFS (40.28 ± 3.68). Histopathological studies showed disruption of cardiac tissues in the DOX groups. Cotreatment with scutellarin reduced the damage to cardiac tissues. In the pharmacokinetic and tissue distribution study, scutellarin reduced the heart tissue exposure to DOX but did not change the AUC of plasma. These results suggest that scutellarin can protect against DOX-induced acute cardiotoxicity through its antioxidant activity and alterations of heart concentrations.
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http://dx.doi.org/10.1007/s12272-017-0907-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5537312PMC
July 2017

Selumetinib Attenuates Skeletal Muscle Wasting in Murine Cachexia Model through ERK Inhibition and AKT Activation.

Mol Cancer Ther 2017 02 6;16(2):334-343. Epub 2016 Sep 6.

Department of Pharmacy, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, P.R. China.

Cancer cachexia is a multifactorial syndrome affecting the skeletal muscle. Previous clinical trials showed that treatment with MEK inhibitor selumetinib resulted in skeletal muscle anabolism. However, it is conflicting that MAPK/ERK pathway controls the mass of the skeletal muscle. The current study investigated the therapeutic effect and mechanisms of selumetinib in amelioration of cancer cachexia. The classical cancer cachexia model was established via transplantation of CT26 colon adenocarcinoma cells into BALB/c mice. The effect of selumetinib on body weight, tumor growth, skeletal muscle, food intake, serum proinflammatory cytokines, E3 ligases, and MEK/ERK-related pathways was analyzed. Two independent experiments showed that 30 mg/kg/d selumetinib prevented the loss of body weight in murine cachexia mice. Muscle wasting was attenuated and the expression of E3 ligases, MuRF1 and Fbx32, was inhibited following selumetinib treatment of the gastrocnemius muscle. Furthermore, selumetinib efficiently reduced tumor burden without influencing the cancer cell proliferation, cumulative food intake, and serum cytokines. These results indicated that the role of selumetinib in attenuating muscle wasting was independent of cancer burden. Detailed analysis of the mechanism revealed AKT and mTOR were activated, while ERK, FoxO3a, and GSK3β were inhibited in the selumetinib -treated cachexia group. These indicated that selumetinib effectively prevented skeletal muscle wasting in cancer cachexia model through ERK inhibition and AKT activation in gastrocnemius muscle via cross-inhibition. The study not only elucidated the mechanism of MEK/ERK inhibition in skeletal muscle anabolism, but also validated selumetinib therapy as an effective intervention against cancer cachexia. Mol Cancer Ther; 16(2); 334-43. ©2016 AACR.
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http://dx.doi.org/10.1158/1535-7163.MCT-16-0324DOI Listing
February 2017

Nilotinib reverses ABCB1/P-glycoprotein-mediated multidrug resistance but increases cardiotoxicity of doxorubicin in a MDR xenograft model.

Toxicol Lett 2016 Sep 1;259:124-132. Epub 2016 Aug 1.

Department of Pharmacy, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 200233 Shanghai, China. Electronic address:

The BCR-Abl tyrosine kinase inhibitor (TKI), nilotinib, was developed to surmount resistance or intolerance to imatinib in patients with Philadelphia-positive chronic myelogenous leukemia. Recent studies have shown that nilotinib induces potent sensitization to anticancer agents by blocking the functions of ABCB1/P-glycoprotein (P-gp) in multidrug resistance (MDR). However, changes in P-gp expression or function affect the cardiac disposition and prolong the presence of both doxorubicin (DOX) and doxorubicinol (DOXol) in cardiac tissue, thus, enhancing the risk of cardiotoxicity. In this study, we used a MDR xenograft model to evaluate the antitumor activity, tissue distribution and cardiotoxicity of DOX when co-administered with nilotinib. This information will provide more insight into the pharmacological role of nilotinib in MDR reversal and the risk of DOX cardiotoxicity. Our results showed that nilotinib significantly enhanced DOX cytotoxicity and increased intracellular rhodamine 123 accumulation in MG63/DOX cells in vitro and strongly enhanced DOX inhibition of growth of P-gp-overexpressing MG63/DOX cell xenografts in nude mice. Additionally, nilotinib significantly increased DOX and DOXol accumulation in serum, heart, liver and tumor tissues. Importantly, nilotinib induced a disproportionate increase in DOXol in cardiac tissue. In the co-administration group, CBR1 and AKR1A1 protein levels were significantly increased in cardiac tissue, with more severe necrosis and vacuole formation. These results indicate that nilotinib reverses P-gp- mediated MDR by blocking the efflux function and potentiates DOX-induced cardiotoxicity. These findings represent a guide for the design of future clinical trials and studies of pharmacokinetic interactions and may be useful in guiding the use of nilotinib in combination therapy of cancer in clinical practice.
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http://dx.doi.org/10.1016/j.toxlet.2016.07.710DOI Listing
September 2016

Missed diagnosis of oesophageal perforation in ankylosing spondylitis cervical fracture: Two case reports and literature review.

J Int Med Res 2016 Feb 5;44(1):170-5. Epub 2016 Jan 5.

Department of Orthopaedic Surgery, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China

Oesophageal perforation after blunt injury cervical fracture in patients with ankylosing spondylitis (AS) is rarely reported. The early diagnosis of oesophageal perforation is extremely important. We present two cases of patients with AS who sustained cervical fracture dislocation and spinal cord injury. The ossified sharp fragments caused oesophageal perforation, and the delayed diagnoses had serious consequences. Oesophageal perforation should be suspected in patients with AS and cervical fracture if bone fragments are pressing against the oesophagus and a gas shadow is visible around the fracture site on computed tomography imaging.
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http://dx.doi.org/10.1177/0300060515614230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5536578PMC
February 2016

Activation of novel estrogen receptor GPER results in inhibition of cardiocyte apoptosis and cardioprotection.

Mol Med Rep 2015 Aug 24;12(2):2425-30. Epub 2015 Apr 24.

Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.

Several studies have recently demonstrated that G protein-coupled estrogen receptor (GPER) 30 directly binds to estrogen and mediates its action. The aim of the present study was to investigate the effects of GPER on cardiocyte apoptosis following ischemia/reperfusion injury (MIRI) in H9C2 myocardial cells. H9C2 cells were treated with a specific GPER agonist (G1), 17β-estradiol (E2) or the vehicle. The cells were subjected to 20 min of myocardial ischemia followed by 120 min of reperfusion. They were then randomly assigned to three experimental groups: Control, G1, E2. B-cell lymphoma 2 (Bcl-2) and Bcl-2 associated X (Bax) levels were measured, Hoechst 33258 staining was performed to assess apoptosis, and superoxide dismutase (SOD), tumor necrosis factor (TNF)-α and adenosine triphosphatase (ATPase) levels were determined. To test the specificity of G1, GPER-knockout cells were treated with G1 and analyzed as stated above. Compared with the vehicle-treated groups, G1 and E2-treated groups exhibited elevated Bcl-2 levels, decreased Bax levels and cell apoptosis, significantly increased SOD and ATP levels and decreased TNF-α levels following ischemia-reperfusion. However, G1 had no evident effects on the GPER-knockout cells. In conclusion, the present study suggested that GPER activation provided a cardioprotective effect following ischemia-reperfusion by inhibiting cardiocyte apoptosis.
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http://dx.doi.org/10.3892/mmr.2015.3674DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4464361PMC
August 2015

[Influence of thymidylate synthase gene polymorphisms on high-dose methotrexate-related toxicities in childhood acute lymphoblastic leukemia].

Zhongguo Dang Dai Er Ke Za Zhi 2015 Jan;17(1):11-4

Department of Pediatrics, First Affiliated Hospital of Hunan Normal University/Hunan Province People's Hospital, Changsha 410005, China.

Objective: To investigate the influence of thymidylate synthase (TS) gene polymorphisms on high-dose methotrexate (HD-MTX)-related toxicities in childhood acute lymphoblastic leukemia (ALL).

Methods: A total of 73 children who were diagnosed with ALL between March 2011 and March 2013 were included into this study. Genomic DNAs were extracted from their peripheral blood. And then the genotypes of TS 5'-UTR were determined by direct DNA sequencing after PCR. The toxicity response of 73 patients receiving HD-MTX chemotherapy were observed and recorded, and plasma MTX concentrations at 42-48 hours after chemotherapy were measured.

Results: The main HD-MTX-related toxicities of 73 patients receiving HD-MTX chemotherapy were neutropenia, decreased hemoglobin level, thrombocytopenia, liver toxicity, mucosal damage, and gastrointestinal reactions. There were no significant differences in the incidence rate of HD-MTX-related toxicities between children with different TS 5'-UTR genotypes after chemotherapy (P>0.05). TS 5'-UTR genotype was not significantly correlated with plasma MTX concentrations at 42-48 hours after chemotherapy (P>0.05).

Conclusions: TS gene polymorphisms have no influence on the incidence of HD-MTX-related toxicities in childhood ALL.
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January 2015

Elucidation of fluoranthene degradative characteristics in a newly isolated Achromobacter xylosoxidans DN002.

Appl Biochem Biotechnol 2015 Feb 9;175(3):1294-305. Epub 2014 Nov 9.

Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, College of Life Science, Northwest University, Xi'an, Shaanxi, 710069, China,

Strain DN002 isolated from petroleum-contaminated soil was identified as Achromobacter xylosoxidans based on morphological and biochemical properties and 16S rRNA phylogeny, and investigated for its potential to utilize numerous polycyclic aromatic hydrocarbons (PAHs) such as fluoranthene and pyrene as sole carbon and energy resource. Biodegradation studies showed that 500 mg(·)l(-1)fluranthene was degraded to 35.6 ± 0.3 mg(·)l(-1) by DN002 after 14 days incubation. During fluoranthene biodegradation, catechol 2,3 dioxygenase (C23O) activity was augmented 1.5 times more than catechol 1,2 dioxygenase (C12O), which indicated that C23O played a major role in fluoranthene degradation by DN002. Protein profiles were examined by sodium dodecyl sulfate polyacrylamide gel electrophoresis and two-dimensional electrophoresis then analyzed by mass spectrometry induced by fluoranthene; a molecular mass range of 18 ∼ 66 kDa proteins were found upregulated compared with the uninduced control sample, including multiple isoenzymes of β-oxidation and dehydrogenases as well as dioxygenases. Besides, some new proteins, i.e., dihydrolipoamide succinyltransferase and aldehyde dehydrogenase family proteins and isocitrate lyase were also synthesized.
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http://dx.doi.org/10.1007/s12010-014-1347-7DOI Listing
February 2015

Evaluation of the pharmacokinetics and cardiotoxicity of doxorubicin in rat receiving nilotinib.

Toxicol Appl Pharmacol 2013 Oct 14;272(1):238-44. Epub 2013 Jun 14.

Department of Pharmacy, Affiliated Sixth People's Hospital, Shanghai Jiao Tong University, 200233 Shanghai, China; School of Pharmacy, Shanghai Jiao Tong University, 200240 Shanghai, China.

Doxorubicin (DOX) is a potent chemotherapy drug with a narrow therapeutic window. Nilotinib, a small-molecule Bcr-Abl tyrosine kinase inhibitor, was reported to reverse multidrug resistance (MDR) mediated by P-glycoprotein (P-gp) transmembrane transporters. The present study aimed to investigate nilotinib's affection on the steady-state pharmacokinetics, disposition and cardiotoxicity of DOX. A total of 24 male Sprague-Dawley rats were randomized into four groups (6 in each) and received the following regimens: saline, intravenous DOX (5mg/kg) alone, and DOX co-administrated with either 20 or 40mg/kg nilotinib. Blood was withdrawn at 12 time points till 72h after DOX injection and the concentrations of DOX and its metabolite doxorubicinol (DOXol) in serum and cardiac tissue were assayed by LC-MS-MS method. To determine the cardiotoxicity, the following parameters were investigated: creatine kinase, lactate dehydrogenase, malondialdehyde, and superoxide dismutase. Histopathological examination of heart section was carried out to evaluate the extent of cardiotoxicity after treatments. The results showed that pretreatment of 40mg/kg nilotinib increased the AUC0-t and Cmax of DOX and DOXol. However, their accumulation in cardiac tissue was significantly decreased when compared with the group that received DOX alone. In addition, biochemical and histopathological results showed that 40mg/kg nilotinib reduced the cardiotoxicity induced by DOX administration. In conclusion, co-administration of nilotinib increased serum exposure, but significantly decreased the accumulation of DOX in cardiac tissue. Consistent with in vitro profile, oral dose of 40mg/kg nilotinib significantly decreased the cardiotoxicity of DOX in rat by enhancing P-gp activity in the heart.
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http://dx.doi.org/10.1016/j.taap.2013.06.002DOI Listing
October 2013

[Study on decellularized laryngeal scaffold in dogs].

Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2013 Jan;48(1):54-60

Department of Otorhinolaryngology Head and Neck Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an 710038, China.

Objective: To explore the survivorship and character of decellularized laryngeal scaffold in pectoralis major muscle flap in canine.

Methods: Eighteen donor larynx in experimental group were decellularized by perfusing sodium dodecyl sulphate. Three of them were used to detect the character of histology. The other fifteen ones were embedded in right pectoralis major muscle flap of acceptor canine. Donor larynx in control group were not perfused. Other experimental procedure was the same as experimental group. The specimens were harvested at two weeks, one month and two months after operation, respectively. Macroscopic view, histological examination and trypan blue staining were performed in the experimental group and control group.

Results: The size of the specimens decreased remarkably into disappearance in control group, there was statistical significance between the experimental group and the control group (which used least significant difference t test P < 0.05). There was only little neutrophils and lymphocytes infiltrating around the laryngeal scaffold at 2 weeks in the experimental group. One month after operation, loose connective tissue begin to form around the laryngeal scaffold. After two months of transplantation, the connective tissue became thicker and the number of blood vessels increased than before. There was a large number of lymphocytes and neutrophil infiltration around the laryngeal specimens in the control group at 2nd week. The perichondrium in the control group was damaged at one month post operation. The cartilage cells could not be detected two months after surgery. The survival rate of cartilage cell between experimental group (86.8% ± 3.2%) and the control group (88.6% ± 3.1%) did not show statistical significance before implantation (χ(2) = 0.19, P > 0.05). The survival rate of cartilage cell decreased insignificantly in experimental group while the survival rate declined obviously in the control group at two weeks and one month after operation, the difference had statistical significance (χ(2) were respectively 5.52 and 20.55, P were respectively < 0.05 and < 0.01), the survival rate of cartilage cell in experimental group was (65.8% ± 2.6%) at two months after operation, while the cartilage cell all disappeared in control group.

Conclusions: Perfused decellularation technique can construct a low immunogenicity laryngeal cartilage scaffold which can survive in the chest muscle package and establish a good blood supplement. The decellularized laryngeal scaffold could be used as a biological scaffold for whole laryngeal reconstruction.
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January 2013

[Effect of glucocorticoid on dendritic cells in children with chronic immune thrombocytopenia].

Zhongguo Dang Dai Er Ke Za Zhi 2013 Feb;15(2):91-4

Department of Hematology, Children's Hospital of Hunan, Changsha, China.

Objective: To investigate the change in dendritic cells (DCs) in children with chronic immune thrombocytopenia (cITP) and the effect of glucocorticoid on DCs in children with cITP.

Methods: Fifteen children with cITP and 20 healthy controls were included in the study. Flow cytometry was used to measure the DC subsets count in the 15 children with cITP before and after glucocorticoid treatment as well as the corresponding values in the 20 healthy controls. The DCs derived from peripheral blood monocytes in children with cITP were cultured in vitro and collected, and their immunophenotypes were determined by flow cytometry.

Results: Before glucocorticoid treatment, the children with cITP showed no notable change in the absolute count of myeloid DCs (mDCs) but showed decreased absolute count of plasmacytoid DCs (pDCs) and increased mDC/pDC ratio compared with the healthy controls (P<0.05). After glucocorticoid treatment, the children with cITP demonstrated increased absolute count of pDCs and decreased absolute count of mDCs and mDC/pDC ratio compared with before treatment (P<0.05). Before glucocorticoid treatment, the children with cITP had significantly higher positive rates of HLA-DR, CD80, CD83 and CD86 on peripheral blood DCs than the healthy controls (P<0.01). All the positive rates were significantly decreased after glucocorticoid treatment (P<0.01), so that there was no significant difference from the healthy controls (P>0.05).

Conclusions: Disproportion and functional disturbance of DC subsets is associated with the pathogenesis of cITP in children. Glucocorticoid can strengthen the immunosuppression of DCs in children with cITP, which may contribute to the effectiveness of glucocorticoid as a treatment.
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February 2013

[Adsorption characteristic and form distribution of silicate in lakes sediments].

Huan Jing Ke Xue 2012 Jan;33(1):135-41

College of Environment and Resources, Inner Mongolia University, Huhhot 010021, China.

Taking surface sediments from the Wuliangsuhai Lake and Daihai Lake as adsorbent, the isothermal adsorption experiments of silicate on sediments were carried out and the adsorption behavior was explained by Langmuir, Freundlich and Temkin crossover-type equations, then the form distribution characters of silicate were studied after adsorption in this work. The results showed that the adsorption behavior of silicate on the two lakes sediments can be linear fitting in the lower concentration dose (< or = 3.00 mg x L(-1)); the sediments from the Wuliangsuhai Lake behaved adsorbing silicate while the sediments from the Daihai Lake behaved releasing silicate under the experimental dose; all of the Langmuir, Freundlich and Temkin crossover-type equations can be used to explain the adsorption behavior of silicate on the two lakes sediments, and the native adsorption silicate (NAS) and equilibrium silicate concentration (ESC(0)) calculated by the three equations could be used to explain the sink and source effects of the sediments from the two lakes; the silicate form distribution in the sediments after adsorption indicated that silicate adsorbed on particles were mainly added on the form of IEF-Si, CF-Si, IMOF-Si and OSF-Si, and the IMOF-Si and OSF-Si had important potential bioavailability.
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January 2012

Evaluation of impact of Herba Erigerontis injection, a Chinese herbal prescription, on rat hepatic cytochrome P450 enzymes by cocktail probe drugs.

J Ethnopharmacol 2012 Jan 2;139(1):104-9. Epub 2011 Nov 2.

Department of Pharmacy, the Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, 600 Yi Shan Road, Shanghai 200233, PR China.

Ethnopharmacological Relevance: Herba Erigerontis injection (HEI), one of the most popular herbal prescription in China, is made from the aqueous extracts of Erigeron breviscapus whole plant. Now HEI is widely used for the treatment of cardiovascular diseases and cerebrovascular diseases such as coronary heart disease, anginapectoris and paralysis.

Aim Of The Study: The purpose of this study was to investigate the in vivo effect of HEI on rat cytochrome P450 enzymes (CYP1A2, CYP2C11, CYP2D4, CYP2E1 and CYP3A2) to assess its safety through its potential to interact with co-administered drugs.

Materials And Methods: Rats were randomly divided into five groups. Rats were intravenous administrated with HEI via the caudal vein at the dosage of 1.8ml/kg or 7.2ml/kg once daily for consecutive 3 days or 14 days. On the fourth or the fifteenth day, a cocktail solution at a dose of 5ml/kg, which contained caffeine (2.5mg/kg), tolbutamide (2.5mg/kg), chlorzoxazone (5mg/kg), midazolam (5mg/kg) and metoprolol (10mg/kg), was injected via the lingual vein to all rats. Then 0.8ml blood samples were collected at a set of time-points. The plasma concentrations of probe drugs were simultaneously determined by HPLC. Pharmacokinetic parameters simulated by DAS software were used for the evaluation of HEI on the activities of rat CYP1A2, CYP2C11, CYP2D4, CYP2E1 and CYP3A2 enzymes. ANOVA and Dunnett's test was used for data analysis.

Results: There were no significant influence of pharmacokinetic parameters of caffeine, tolbutamide and chlorzoxazone in HEI pretreated rats. But many pharmacokinetic parameters of metoprolol and midazolam in HEI pretreated rats were affected significantly (P<0.05), which indicated that metabolism of metoprolol and midazolam in these treatment groups was evidently slowed down.

Conclusions: The results from the present in vivo study suggested that HEI showed no effects on rat CYP1A2, CYP2C11 and CYP2E1, however, it demonstrated potential inhibitory effects on rat CYP2D4 and CYP3A2. Therefore, caution is needed when HEI is co-administered with drugs metabolized by human CYP2D6 or CYP3A4 in clinic, which may result in increased concentrations of these drugs and relevant herb-drug interactions.
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http://dx.doi.org/10.1016/j.jep.2011.10.019DOI Listing
January 2012

Alleviation of the acute doxorubicin-induced cardiotoxicity by Lycium barbarum polysaccharides through the suppression of oxidative stress.

Food Chem Toxicol 2011 Jan 5;49(1):259-64. Epub 2010 Nov 5.

Center of Safety Evaluation, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang, China.

The present study aims to investigate whether Lycium barbarum polysaccharides (LBP) could protect against acute doxorubicin (DOX)-induced cardiotoxicity. Rats received daily treatment of either distilled water (4 ml/kg) or LBP (200mg/kg) for 10 days and then followed by an intravenous injection at day 7 of either saline (10 ml/kg) or DOX (10 mg/kg). DOX induced significantly myocardial damage in rats, which were characterized as conduction abnormalities, decreased heart-to-body weight ratio, increased serum CK, and myofibrillar disarrangement. DOX treatment also increased MDA and decreased SOD and GSH-Px activity in cardiac tissues. Pretreatment with LBP significantly reduced DOX-induced oxidative injury in cardiac tissue, suggesting by the fact that LBP significantly attenuated DOX-induced cardiac myofibrillar disarrangement and LBP was effective in decreasing the levels of serum CK and thus improving conduction abnormalities caused by DOX. LBP treatment significantly increased SOD and GSH-Px activity and decreased the MDA level of heart tissues damaged by DOX exposure in rats. Furthermore, the cytotoxic study showed that LBP protect against cytotoxicity of DOX in cardiac myoblasts H9c2 but dose not attenuate the anti-tumor activity of DOX. In summary, our evidence indicates that LBP elicited a typical protective effect on DOX-induced acute cardiotoxicity via suppressing oxidative stress.
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http://dx.doi.org/10.1016/j.fct.2010.10.028DOI Listing
January 2011

Effects of quercetin on gene and protein expression of NOX and NOS after myocardial ischemia and reperfusion in rabbit.

Cardiovasc Ther 2009 ;27(1):28-33

Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Previous studies have suggested that reactive oxygen species (ROS), endothelial nitric oxide synthase (eNOS), and inducible nitric oxide synthase (iNOS) are involved in the pathophysiology of myocardial ischemia-reperfusion injury (MIRI). The NOX family of NADPH oxidases share the capacity to generate superoxide and ROS. Several studies have demonstrated that quercetin possesses a protective effect against MIRI. Our aim is to investigate the effects of quercetin on NOX2, eNOS, and iNOS after MIRI in rabbits. New Zealand rabbits were subjected to 30 min of myocardial ischemia followed by 12 h of reperfusion. They were then randomly assigned to four experimental groups: control, I/R (ischemia/reperfusion), quercetin (Que), I/R + Que. Gene and protein expression of NOX2, eNOS, and iNOS were compared. Both in real-time PCR and in the Western blotting studies, myocardial ischemia-reperfusion-induced NOX2 and iNOS expression were enhanced (P < 0.01) but eNOS mRNA and protein expression in I/R hearts were not significantly different from those in control (P < 0.01). Administration of quercetin reduced NOX2, eNOS, and iNOS mRNA and protein expression both in control and in I/R heart (P < 0.01). Gene and protein expression of NOX2 and iNOS were increased after MIRI. Quercetin not only inhibited myocardial ischemia-reperfusion-induced NOX2 and iNOS mRNA and protein expression but also inhibited eNOS mRNA and protein expression.
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http://dx.doi.org/10.1111/j.1755-5922.2009.00071.xDOI Listing
March 2009

[Investigation on effect of PVP on morphological changes and crystallization behavior of nylon 6 in PVP/nylon 6 blends by FTIR spectroscopy].

Guang Pu Xue Yu Guang Pu Fen Xi 2008 Sep;28(9):2048-52

State Key Laboratory of Polymer Physics and Chemistry, Joint Laboratory of Polymer Science and Materials, Beijing National Laboratory for Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.

Temperature-dependent FT IR, DSC and POM were used to investigate the interaction between PVPK90 and nylon 6 molecules and its effect on the thermal behavior and morphology of nylon 6. DSC results suggest that the melting and crystallization behavior of nylon 6 are obviously influenced by the introduction of PVP. With the PVP content increasing, the crystallization temperature, melting temperature and the crystallinity of nylon 6 decreased, and eventually, both the exothermal and endothermic peaks could not be observed when the PVP content reached 80%, implying that the aggregation structure of nylon 6 changes from the crystalline state to the amorphous state. FTIR provided the evidence of the interaction between PVP and nylon 6 molecules. With the increase in PVP content, the peak position of nu N-H of nylon 6 gradually shifts from 3311 to 3300 cm(-1) with 90% content of PVP, and the half height peak width is broadened correspondingly. Three peaks were obtained in the carbonyl group absorption band for PVPK90/Nylon 6(50/50) and PVPK90/Nylon 6(80/20) blends from the curve-fitting results. With the addition of PVP molecules, the nu C=O of nylon 6 shifts to higher wave number and a new peak located at about 1620 cm(-1) appears and its peak area increases with the content of PVP. The above spectral variation of nu C=O and nu N-H in the PVPK90/Nylon 6 blend indicates that the carbonyl group of PVP could form H-bonding with N-H group of nylon 6 molecule, and partially destroy the hydrogen bonding between the nylon 6 molecules. POM results showed that the spherulitic size of nylon 6 decreases with the increment of the PVP and becomes more imperfect, and when the PVP content reaches 80%, no spherulites could be observed. This phenomenon is attributed to the molecular interactions between the PVP and the nylon 6 molecules, which weakens the free mobility of nylon 6 chains to form regular packing and eventually induces the change in the spherulitic morphology of nylon 6. In summary, the molecular interactions between the carbonyl group of PVP molecules and N-H group of nylon 6 molecules account for the above changes in the crystalline structure and the morphology of nylon 6 in the blends.
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September 2008

[Establishment of the guinea pig model of synovial tuberculosis of knee joint by mycobacterium tuberculosis H37Rv infection].

Sichuan Da Xue Xue Bao Yi Xue Ban 2006 Sep;37(5):804-6, 809

Department of Orthopedic Surgery, West China Hospital, Sichuan University, Chengdu 610041, China.

Objective: To explore how to establish the guinea pig model of synovial tuberculosis of knee joint by mycobacterium tuberculosis H37Rv infection.

Methods: Two doses (1 x 10(7)/mL, 50 microL and 100 microL) of Mycobacterium strains were injected into the knee joint of the guinea pig that had been immunized and allergized with Freund's complete adjuvant six weeks previously. The pathological changes of the synovial membrane, cartilage and bone after infection of mycobacterium tuberculosis were investigated. At the same time, the synovial membrane tissues and culture for the mycobacterium tuberculosis were collected and examined.

Results: After the infection of mycobacterium tuberculosis H37Rv, the knee joint of guinea pig became swollen, but the interference to the whole conditions of the guinea pig was slight in both infection groups. The tissue sections of the synovial membrane showed tubercle and caseous necrosis of the knee joint in both groups. The mycobacterium tuberculosis could be detected by using Ziehl-neelsen stain and the culture from the synovial membrane of the knee joint.

Conclusion: By injecting suitable dosage of mycobacterium H37Rv strains into the joint of the immunized and allergized guinea pig, we have established the guinea pig model of synovial tuberculosis that is pathologically similar to synovial tuberculosis in humans, so it is fit for use in the diagnostic studies and pathological researches.
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September 2006

[Investigation of follicular development and oocyte maturation after cryopreservation and xenograft of newborn mouse ovaries].

Sheng Li Xue Bao 2006 Feb;58(1):41-6

The Laboratory of Developmental Biology, Xinhua Hospital, School of Medical Sciences, Shanghai Jiaotong University, Shanghai 200092, China.

In order to explore the feasibility of cryopreserving primordial follicles in attaining their developmental competence following freezing and thawing, ovaries from newborn mice were cryopreserved and the thawed ovaries were xenografted into kidney capsules of adult female mice. Ovaries were isolated from newborn B6C2F(1) female mice, infiltrated by Leibovitz 15 (L-15) medium containing 10% (V/V) fetal bovine serum (FBS) and 1.5 mol/L dimethylsulfoxide (DMSO), and then packed into 0.25 ml plastic straws. The ovaries contained in straws were frozen under nitrogen vapour at -40 degrees C in Cryocell 1200 programmable freezer, and stored in liquid nitrogen for periods ranging from 1 week to 6 months. Upon thawing, the straws were dipped into room temperature water for 10~20 s, after which the ovaries were collected and washed in L-15 buffer containing 10% (V/V) FBS without DMSO to remove cryoprotectant. The thawed ovaries were transplanted into kidney capsules of 8~12-week old adult B6C2F(1) female recipient mice by two protocols, with either 1 or 2 ovaries in each capsule. Upon withdrawal after at least 14 d of transplantation, only 45.00% (72/160) of the ovaries were recovered from 40 recipients transplanted with 2 ovaries in each capsule, compared to 82.50% (33/40) in 20 recipients with only 1 ovary in each capsule. The grafted ovaries exhibited similar follicular developmental progression to that of natural ovaries. There were antral follicles present in the transplanted ovaries on day 14, whose number increased more substantially on day 19 after transplantation. Following stimulation of the recipient mice with 10 IU PMSG on day 19 after xenografting, follicles further developed to preovulatory stage with appearance of cumulus oocytes and enlarged antrum. Oocytes from these fully grown antral follicles were collected and matured in vitro in modified essential medium-alpha (MEMalpha). After 16~17 h of culture, 40.90% of the oocytes exhibited germinal vesicle breakdown (GVBD) and among which 89.02% proceeded to the metaphase II (MII) stage as indicated by exclusion of the first polar body. The remaining oocytes were further cultured and 50.83% of which initiated GVBD by 20~21 h of culture, but only 21.40% of which proceeded to MII. The above results demonstrated that the primordial follicles in newborn mouse ovaries were capable of sustaining freezing and thawing, and reinitiating development following xenograft into kidney capsule in adult recipient female mice. Production of mature oocytes from such re-developed follicles following gonadotrophin priming and the subsequent oocyte in vitro maturation implied immense prospect of application of this method to preserve female germ cells, conserve endangered species, establish animal gene stock, and utilize oocytes in assisted reproductive techniques.
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February 2006