Publications by authors named "Meiyu Zhang"

47 Publications

Modification of EDC method for increased labeling efficiency and characterization of low-content protein in gum acacia using asymmetrical flow field-flow fractionation coupled with multiple detectors.

Anal Bioanal Chem 2021 Aug 20. Epub 2021 Aug 20.

Department of Chemistry, Hannam University, Daejeon, 34054, South Korea.

1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) is widely used as a crosslinker for fluorescence labeling of protein in the fields of biochemistry and food analysis. Many natural polysaccharides often contain some proteins or peptides that are very low in content but play a vital role in their biological function as well as technical applications. Determination of these low-content proteinaceous matters requires a highly sensitive and selective method. In this study, a methodological approach for investigations of the presence of proteinaceous material over the molar mass distribution (MD) of polysaccharides was developed using gum acacia (GA) as a model polysaccharide. EDC fluorescence-labeling method was modified by changing the pH (7, 9, and 11) of the solution for the analysis of low-content protein in food materials. Fluorescence spectroscopy and asymmetrical flow field-flow fractionation (AF4) were employed for characterizing the labeling efficiency and physiochemical properties of unlabeled and fluorescence-labeled GA. AF4 provided molar mass (M) and the radius of gyration (r) of arabinogalactan (AG) and arabinogalactan protein complex (AGP) and determined the presence of proteinaceous matter over the MD. The labeling efficiencies of GA at pH 7, 9, and 11 determined by fluorescence spectroscopy were 56.5, 68.4, and 72.0%, respectively, with an increment of 15.5% when pH was increased from 7 to 11. The modified EDC fluorescence-labeling method allows highly sensitive and selective analysis of low-content proteinaceous matters and their distribution in natural polysaccharides.
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http://dx.doi.org/10.1007/s00216-021-03587-yDOI Listing
August 2021

ZNF326 promotes colorectal cancer epithelial-mesenchymal transition.

Pathol Res Pract 2021 Sep 22;225:153554. Epub 2021 Jul 22.

Department of Pathology, College of Basic Medical Science, and the First Affiliated Hospital of China Medical University, Shenyang, China. Electronic address:

Zinc-finger protein 326 (ZNF326) activity has been reported in different tumors, but its expression and possible mechanism of action in colorectal cancer are not known. In this study, we applied immunohistochemistry to detect the expression of ZNF326 in colorectal tissues. Next, we used a ZNF326 expression plasmid and small interfering (si) RNA-ZNF326 (siZNF326) to transfect colorectal cancer cell lines in order to determine the effect of ZNF326 on cell migration and as well as its potential role in promoting epithelial-mesenchymal transition (EMT). A higher ZNF326 expression in the nuclei of colorectal tumor cells compared to normal mucosa was observed (70.3%, 109/155 specimens vs. 23.2%, 36/155 specimens). A high ZNF326 expression level was positively correlated with tumor differentiation, tumor-node-metastasis (TNM) staging, and lymph node metastasis. Transfection of cancer cell lines (SW480 and SW620) with a ZNF326-overexpression vector promoted colorectal cancer cell invasion and altered the expression of EMT-related proteins. Vimentin, N-cadherin, Snail, and Slug were upregulated, whereas E-cadherin and zonula occludens-1 (ZO-1) were downregulated. In contrast, downregulation of ZNF326 expression using siRNA-ZNF326 in cancer cell lines (CL187 and RKO) resulted in the opposite findings. ZNF326 overexpression also upregulated the expression of latent transforming growth factor beta binding protein 4 (LTBP4) and p-Smad2/3. In conclusion, ZNF326 promoted the EMT and invasiveness of colorectal cancer cells. These findings are likely due to LTBP4 and p-Smad2/3 upregulation and, in turn, transforming growth factor beta (TGF-β) signaling activation.
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http://dx.doi.org/10.1016/j.prp.2021.153554DOI Listing
September 2021

Simultaneous determination of multiple polypeptide antibiotics residues in lake water by lyophilization combined with liquid chromatography-tandem mass spectrometry.

Anal Sci 2021 May 21. Epub 2021 May 21.

Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics, Development and Safety Evaluation, South China Agricultural University.

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http://dx.doi.org/10.2116/analsci.21P037DOI Listing
May 2021

ST-AFN: a spatial-temporal attention based fusion network for lane-level traffic flow prediction.

PeerJ Comput Sci 2021 22;7:e470. Epub 2021 Apr 22.

College of Computer Science and Technology, Zhejiang University of Technology, Hangzhou, China.

Traffic flow prediction is the foundation of many applications in smart cities, and the granular precision of traffic flow prediction has to be enhanced with refined applications. However, most of the existing researches cannot meet these requirements. In this paper, we propose a spatial-temporal attention based fusion network (ST-AFN), for lane-level precise prediction. This seq2seq model consists of three parts, namely speed process network, spatial encoder, and temporal decoder. In order to exploit the dynamic dependencies among lanes, attention mechanism blocks are embedded in those networks. The application of deep spatial-temporal information matrix results in progresses in term of reliability. Furthermore, a specific ground lane selection method is also proposed to ST-AFN. To evaluate the proposed model, four months of real-world traffic data are collected in Xiaoshan District, Hangzhou, China. Experimental results demonstrate that ST-AFN can achieve more accurate and stable results than the benchmark models. To the best of our knowledge, this is the first time that a deep learning method has been applied to forecast traffic flow at the lane level on urban ground roads instead of expressways or elevated roads.
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http://dx.doi.org/10.7717/peerj-cs.470DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080424PMC
April 2021

p53 Promoted Ferroptosis in Ovarian Cancer Cells Treated with Human Serum Incubated-Superparamagnetic Iron Oxides.

Int J Nanomedicine 2021 12;16:283-296. Epub 2021 Jan 12.

Key Laboratory of Pathobiology, Ministry of Education, Department of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun 130021, People's Republic of China.

Methods: In this study, we used MTT assays to demonstrate that a combination of SPIO-Serum and wild-type p53 overexpression can reduce ovarian cancer cell viability . Prussian blue staining and iron assays were used to determine changes in intracellular iron concentration following SPIO-Serum treatment. TEM was used to evaluate any mitochondrial damage induced by SPIO-Serum treatment, and Western blot was used to evaluate the expression of the iron transporter and lipid peroxidation regulator proteins. JC-1 was used to measure mitochondrial membrane potential, and ROS levels were estimated by flow cytometry. Finally, xCT protein expression and mitochondrial ROS levels were confirmed using fluorescence microscopy.

Results: SPIO-Serum effectively induced lipid peroxidation and generated abundant toxic ROS. It also facilitated the downregulation of GPX4 and xCT, ultimately resulting in iron-dependent oxidative death. These effects could be reversed by iron chelator DFO and lipid peroxidation inhibitor Fer-1. SPIO-Serum treatment disrupted intracellular iron homeostasis by regulating iron uptake and the cells presented with missing mitochondrial cristae and ruptured outer mitochondrial membranes. Moreover, we were able to show that p53 contributed to SPIO-Serum-induced ferroptosis in ovarian cancer cells.

Conclusion: SPIO-Serum induced ferroptosis and overexpressed p53 contributed to ferroptosis in ovarian cancer cells. Our data provide a theoretical basis for ferroptosis as a novel cell death phenotype induced by nanomaterials.
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http://dx.doi.org/10.2147/IJN.S282489DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811475PMC
January 2021

Vitamin K2 Suppresses Proliferation and Inflammatory Cytokine Production in Mitogen-Activated Lymphocytes of Atopic Dermatitis Patients through the Inhibition of Mitogen-Activated Protein Kinases.

Biol Pharm Bull 2021 ;44(1):7-17

Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences.

Vitamin K2 is suggested to have a suppressive effect on the peripheral blood mononuclear cells (PBMCs) of pediatric atopic dermatitis patients. We examined the molecular targets of vitamin K2 to suppress proliferation and cytokine production in T-cell mitogen-activated PBMCs of atopic dermatitis patients from the viewpoint of mitogen-activated protein kinase signaling molecules. The study population included 16 pediatric vitamin K2 patients and 21 healthy subjects. The effect of vitamin K2 on concanavalin A-activated PBMC proliferation was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and cell counting assays. T-helper (Th)1/Th2/Th17 cytokine profiles in plasma and PBMC-culture supernatants were analyzed by a cytometric beads array assay. Mitogen-activated protein kinase signaling molecules in concanavalin A-activated PBMCs were examined by enzyme-linked immunosorbent assay (ELISA) assays. At 10-100 µM, vitamin K2 significantly suppressed the proliferation of mitogen-activated PBMCs derived from atopic dermatitis patients and healthy subjects (p < 0.05). The interleukin (IL)-10 concentrations in plasma and the PBMC culture supernatants of atopic dermatitis patients were significantly higher than those of healthy subjects (p < 0.05). The IL-2 concentrations in the culture supernatants of atopic dermatitis PBMCs were significantly lower than those of healthy PBMCs (p < 0.05). Vitamin K2 significantly inhibited the IL-17A, IL-10, and tumor necrosis factor α (TNF-α) production (p < 0.05), and increased the IL-2 production (p < 0.01) in the culture supernatant of atopic dermatitis PBMCs. At 10-100 µM, vitamin K2 markedly decreased the of Mek1, extracellular signal-regulated kinases (ERK)1/2 mitogen-activated protein kinase, and SAPK/c-Jun N-terminal kinase (JNK) expression in atopic dermatitis PBMCs (p < 0.05). Vitamin K2 is suggested to attenuate activated T-cell immunity in atopic dermatitis patients through the inhibition of mitogen-activated protein kinase-Mek1-ERK1/2 and SAPK/JNK signaling pathways.
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http://dx.doi.org/10.1248/bpb.b20-00079DOI Listing
August 2021

A homogeneous Cu-based polyoxometalate coupled with mesoporous TiO for efficient photocatalytic H production.

J Colloid Interface Sci 2021 Apr 7;587:613-621. Epub 2020 Nov 7.

State Key Laboratory of Applied Organic Chemistry, Key Laboratory of Nonferrous Metals Chemistry and Resources Utilization of Gansu Province, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, China; State Key Laboratory for Oxo Synthesis and Selective Oxidation, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000, China. Electronic address:

Developing a photocatalytic system for water splitting to H is a promising strategy to address fossil fuel consumption. Exploring photocatalysts with high-performance, steady and low-cost has been the essential goals toward photo-reduction of water. Herein, noble-metal-free polyoxometalate Na[(α-SbWO)Cu(HO)]·46HO (CuPOM) was coupled with mesoporous, multiphase TiO (Meso-TiO) for the first time to catalyze hydrogen production. The composite system exhibited excellent photocatalytic hydrogen production activity. After 2.5 h of illumination, the activity was enhanced 77 times (1284.8 μmol/g) in the presence of CuPOM compared to the blank Meso-TiO (16.6 μmol/g). Nitrogen adsorption-desorption isotherms results reveal the mesoporous characteristics of Meso-TiO which could increase the active sites of the reaction. The cycling experiment demonstrated the composite system remained stable after five cycles without activity loss. Multiple characterizations reveal that Ti is generated after the reaction, which further narrows the band gap and promotes the photocatalytic performance of the composite system. The suitable LUMO energy level of CuPOM was confirmed by electrochemical tests. It accelerates the transfer of photo-generated electrons from the CB of Meso-TiO to the protons in the solution, resulting in a high photocatalytic H production performance. The combination of Meso-TiO with reductive polyoxometalate innovatively provides novel insights into the design of efficient photocatalytic materials for H production.
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http://dx.doi.org/10.1016/j.jcis.2020.11.018DOI Listing
April 2021

PWP1 Promotes the Malignant Phenotypes of Lung Cancer Cells by Interacting with DVL2 and Merlin.

Onco Targets Ther 2020 8;13:10025-10037. Epub 2020 Oct 8.

Department of Pathology, College of Basic Medical Science, and First Affiliated Hospital of China Medical University, Shenyang, People's Republic of China.

Purpose: The significance of periodic tryptophan protein 1 (PWP1) expression in human cancer and its molecular mechanism of action have not been reported so far.

Materials And Methods: Immunohistochemistry was performed to analyze the expression of PWP1 in non-small cell lung cancer (NSCLC) tissues and statistical analysis was applied to analyze the relationship between PWP1 expression and the clinicopathological factors. The effects of PWP1 on NSCLC proliferation and invasion were determined by colony formation, transwell and MTT assays. Western blot analysis (WB), dual-luciferase reporter gene assays and immunofluorescence staining were performed to demonstrate whether PWP1 stimulates Wnt pathway and inhibits Hippo pathway. Co-immunoprecipitation (Co-ip) assays were used to confirm the potential role of PWP1 in Wnt and Hippo signaling pathways.

Results: PWP1 expression in NSCLC was higher than that in normal bronchial epithelium and normal submucosal glands. In addition, PWP1 expression had a positive correlation with poor differentiation, high pathological tumor-node-metastasis (TNM) stage, and lymph node metastasis. Kaplan-Meier database demonstrated that the overall survival time of patients with high PWP1 expression was significantly shorter than that of patients with low PWP1 expression. Mechanistically, we found that PWP1 could interact with DVL2 to upregulate β-catenin (thereby activating the Wnt pathway), whereas PWP1 could interact with Merlin (NF2) to downregulate p-MST1 (thereby inhibiting the Hippo signaling pathway). The effects of PWP1 on promoting the Wnt pathway or inhibiting the Hippo pathway were offset in DVL2- or Merlin-knockdown cells transiently overexpressing PWP1.

Conclusion: PWP1 expression in NSCLC was correlated with poor prognosis. PWP1 enhanced the activity of the Wnt pathway by interacting with DVL2, whereas PWP1 inhibited the activity of the Hippo pathway by interacting with Merlin. Together, these two effects promoted the detrimental biological behaviors of NSCLC cells.
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http://dx.doi.org/10.2147/OTT.S263815DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7553635PMC
October 2020

Pharmacokinetics, Activity, and Residue Elimination of - and -Diclazuril in Broiler Chickens.

J Agric Food Chem 2020 Aug 7;68(33):8987-8995. Epub 2020 Aug 7.

National Reference Laboratory of Veterinary Drug Residues, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.

Diclazuril (DIC) is widely used as a racemic mixture to prevent and treat coccidiosis in farm animals, while the pharmacokinetics, bioactivity, and toxicity of DIC enantiomers are not known at all. This study first established a simple, sensitive, and reliable liquid chromatography tandem mass spectrometry method for separation of -DIC and -DIC and their analyses. Then, it was applied to investigate the stereoselective pharmacokinetics and residual elimination of individual enantiomers, and their anticoccidial activity was also evaluated in broiler chickens. The results indicated that the area under the concentration-time curve (AUC) and elimination half-life () were significantly different ( < 0.05) for two enantiomers in chicken plasma. The AUC and of -DIC were approximately 2 and 1.4 times those of -DIC, respectively. The residual elimination of DIC enantiomers in chicken tissues was also stereoselective. The concentrations of -DIC in chicken muscle and liver were greater than those of -DIC, and it is the opposite in the kidney. There was no significant difference ( > 0.05) in the anticoccidial activity of racemate and enantiomers when a single enantiomer in feed was added above 0.5 mg kg. However, the anticoccidial activity of -DIC (0.25 mg kg) was significantly higher ( < 0.05) than that of -DIC (0.25 mg kg) in the diet. It should be mentioned that in chicken small intestine and cecum, the enantiomerization rate of each enantiomer in the infection group was faster than that in the uninfected group.
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http://dx.doi.org/10.1021/acs.jafc.0c03091DOI Listing
August 2020

HPLC semi-preparative separation of diclazuril enantiomers and racemization in solution.

J Sep Sci 2020 Apr 15;43(7):1240-1247. Epub 2020 Jan 15.

School of Chemistry, South China Normal University, Guangzhou, P. R. China.

Diclazuril has been widely used in poultry feed for prevention and treatment of coccidiosis, and its chiral separation is rarely reported. Herein, semi-preparative separation method of diclazuril enantiomers has been developed through normal-phase high-performance liquid chromatography. Effects of chiral stationary phases, alcoholic modifiers, and column temperature on separation of diclazuril were discussed in detail. Both the single-urea-bound 4-chlorophenylcarbamoylated β-cyclodextrin and amylose tris(3,5-dimethylphenylcarbamate)-coated chiral stationary phases showed strong ability in separation of diclazuril by using n-hexane-trifluoroacetic acid-ethanol. Then, semi-preparative separation of diclazuril was carried out through stacked injection, and the "enantiomeric excess" purities of two fractions were over 98%. Next, the electronic circular dichroism profiles of these two fractions in ethanol solution displayed the mirror image of each other in the range 360-200 nm. Moreover, effects of acidic/basic additive, time, and temperature on racemization of diclazuril enantiomers in ethanol solution have been studied in detail through normal-phase high-performance liquid chromatography. Racemization of diclazuril enantiomers was remarkably accelerated through adding triethylamine at high temperature. We envision that this systematic investigation of diclazuril at an enantiomeric level would provide valuable information in future studies involving enantioselective bioactive, metabolic, and toxicological activities.
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http://dx.doi.org/10.1002/jssc.201901201DOI Listing
April 2020

Molecular Mechanisms of Tyrosine Kinase Inhibitor Resistance Induced by Membranous/Cytoplasmic/Nuclear Translocation of Epidermal Growth Factor Receptor.

J Thorac Oncol 2019 10 19;14(10):1766-1783. Epub 2019 Jun 19.

Department of Pathology, College of Basic Medical Sciences and First Affiliated Hospital of China Medical University, Shenyang, China. Electronic address:

Introduction: The molecular mechanism underlying the induction of resistance to tyrosine kinase inhibitors (TKIs) via the membranous/cytoplasmic/nuclear translocation of EGFR has not yet been reported.

Methods: We performed immunohistochemistry to detect the distribution of EGFR in lung adenocarcinoma specimens after TKI treatment and analyzed the relationship between different EGFR locations and patient survival duration. Mass spectrometry analysis and immunoprecipitation were performed to show the interaction of cytosolic EGFR with YY1 associated protein 1 (YAP) and salt inducible kinase 2 (SIK2). Dual-luciferase assays, immunoblotting, real-time polymerase chain reaction, and functional experiments were used to elucidate the role of EGFR cytoplasmic/nuclear translocation in Hippo pathway dysregulation.

Results: Patients with advanced lung adenocarcinoma with membranous mutant EGFR (19del or 21 L858R) showed significantly longer progression-free survival than those with cytoplasmic mutant EGFR after gefitinib treatment. The concentration that inhibits 50% in PC-9 with cytoplasmic EGFR was higher than that in hunman non-small cell lung cancer 827 with membranous EGFR. During first-generation TKI resistance induction, membrane EGFR translocated to the cytoplasm/nucleus, accompanied by the Hippo pathway inhibition. Cytoplasmic EGFR and SIK2 interaction inhibited large tumor suppressor kinase 1 (LATS1) and macrophage stimulating 1 (MST1) interaction, promoting YAP nuclear translocation. However, cells with osimertinib-induced resistance also showed EGFR translocation and lower phospho-EGF receptor but did not show Hippo pathway inhibition. Moreover, osimertinib and erlotinib could restore sensitivity to each other in resistant cells.

Conclusions: Plasma/nuclear translocation of EGFR and inhibition of the Hippo pathway are some of the important mechanisms underlying the resistance induced by first-generation TKIs. Membrane/plasma translocation of EGFR induced by osimertinib may be another resistance phenomenon besides MNNG HOS transforming gene (c-MET) amplification, C797S mutation, and ERK pathway inhibition.
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http://dx.doi.org/10.1016/j.jtho.2019.06.014DOI Listing
October 2019

Determination of residual enantiomers of diclazuril in chicken edible tissues by high performance liquid chromatography.

J Chromatogr B Analyt Technol Biomed Life Sci 2019 Jun 22;1118-1119:203-209. Epub 2019 Apr 22.

National Reference Laboratory of Veterinary Drug Residues (SCAU), College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China. Electronic address:

A convenient, simple, selective and reliable method was established for separating diclazuril enantiomers and detecting their residues in chicken edible tissues by using high-performance liquid chromatography. The potential effects of chiral column, mobile phase and column temperature on chiral separation of racemic diclazuril were evaluated. Average recovery rates of R-diclazuril and S-diclazuril in three spiking levels ranged from 84.3% to 109.5%, and the relative standard deviations were <15.8%. The limits of quantification of two enantiomers were all 25 ng g in all chicken tissues. The method proposed was successfully applied to monitor distributions and residue elimination of diclazuril enantiomers in chicken muscle, liver, kidney and fat following oral administration. There are no obvious differences (p > 0.05) between R-diclazuril and S-diclazuril in the same tissue for each sampling time. The elimination rates in liver were the fastest and the residual time in kidney was the longest. These results can help further evaluate pharmokinetics, pharmodynamics and toxicity of each enantiomer of diclazuril in food-producing animals.
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http://dx.doi.org/10.1016/j.jchromb.2019.04.042DOI Listing
June 2019

Rapid multiresidue analysis of authorized/banned cyclopolypeptide antibiotics in feed by liquid chromatography-tandem mass spectrometry based on dispersive solid-phase extraction.

J Pharm Biomed Anal 2019 Jun 26;170:234-242. Epub 2019 Mar 26.

National Reference Laboratory of Veterinary Drug Residues (SCAU), College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China; Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou, 510642, China. Electronic address:

An effective analytical strategy was developed for simultaneous determination of seven cyclopolypeptide antibiotics (vancomycin, polymyxin B, polymyxin E, teicoplanin A2, bacitracin A, daptomycin and virginiamycin M1) in feed using liquid chromatography-tandem mass spectrometry. The extraction of sample was based on acidified methanol-aqueous solution, followed by a simply dispersive solid-phase extraction for further purification with primary secondary amine as an adsorbent. The method showed good linearity for target analytes in the experimental concentration ranges. At three spiked concentration levels of 50, 100 and 200 μg/kg, the average recoveries for target compounds were in the range of 63.1%-107.5% with the relative standard deviations less than 14.7%. Matrix effects in different feeds were evaluated and the strong signal suppression (>50%) was observed. Compared with the corresponding methods in literature, the developed method is more economical, more sensitive and involves the detection of authorized/banned cyclopolypeptides in animal feed. The proposed method was successfully applied to the routine supervision and rapid screening of cyclopolypeptide antibiotics in complete and premix feed.
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http://dx.doi.org/10.1016/j.jpba.2019.03.050DOI Listing
June 2019

LRRK2 is involved in the pathogenesis of system lupus erythematosus through promoting pathogenic antibody production.

J Transl Med 2019 01 22;17(1):37. Epub 2019 Jan 22.

Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.

Background: Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by the presence of pathogenic autoantibodies associated with polyclonal B cell hyperreactivity. Previous study reported that autophagy-related gene Leucine-rich repeat kinase 2 (LRRK2) was likely a susceptible gene for SLE. However, the pathogenic function of LRRK2 in SLE is undefined.

Methods: Using quantitative PCR, we compared the expression levels of LRRK2 in B cells between SLE patients and healthy controls. The expression levels of LRRK2 in in vitro induced CD19 B cells and naïve B cells were compared as well based on RNA-seq assay. A pristane-induced lupus-like mouse model was used to explore the effects of LRRK2 on the development of SLE. IgG level, B cell subsets in the spleens and bone marrows and pathological features in the kidneys were compared between wildtype (WT) and Lrrk2 littermates.

Results: It was obvious that LRRK2 expression was dramatically up-regulated in primary B cells from SLE patients compared to those from healthy controls, as well as in activated CD19 B cells. More significantly, LRRK2 expression in B cells was positively correlated with system lupus erythematosus disease activity index (SLEDAI), an indicator for disease severity, and serum IgG levels in SLE patients. Negative correlations were observed between LRRK2 expression and serum C3 or C4 levels, two clinical features associated with SLE-related nephritis. LRRK2 deficiency reduced the death rate of pristane treated mice. Decreased levels of total IgG and autoantibody were detected in the serum with less deposition of immune complexes and attenuated pathological symptoms in the kidneys of Lrrk2 mice. Consistent with the reduction in IgG production, the percentages of germinal center B cells and plasma cells decreased significantly as well with LRRK2 deficiency.

Conclusions: Our study demonstrates that LRRK2 expression is upregulated in B cells from SLE patients with strong correlations to disease severity. LRRK2 deficiency largely attenuates the pathogenic progress of lupus-like features in pristane-induced mice. This is probably achieved through affecting B cell terminal differentiation and subsequent immunoglobulin production.
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http://dx.doi.org/10.1186/s12967-019-1786-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6343316PMC
January 2019

PD-1 blockade augments humoral immunity through ICOS-mediated CD4 T cell instruction.

Int Immunopharmacol 2019 Jan 16;66:127-138. Epub 2018 Nov 16.

Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address:

Successful applications of PD-1/PD-L1 blockade in multiple cancers highlight the efficacy of immunotherapy mediated by enhancing CD8 T cell immunity both in mouse and human. How PD-1 blockade affects humoral immunity remains unclear. Herein we demonstrated that treatment of anti-PD-1 antibody led to the increase in both total IgG and OVA-specific IgG in OVA-immunized mice. However, no effect was observed on Ab affinity maturation. Accumulation of germinal center (GC) and memory B cells was observed in the spleens together with elevated percentages of plasma cells in the spleens and bone marrow. More interestingly, dramatic infiltration of CD4 T cells was apparent in GCs after PD-1 blockade with a significant increase in the expression of ICOS. When CD4 T cells and B cells from OVA-immunized mice were co-cultured with neutralizing anti-PD-1 Ab in vitro, PD-1 blockade recapitulated the up-regulation of ICOS expression on CD4 T cells with the activation of ERK signaling. Suppression of ERK activation not only reduced ICOS expression on CD4 T cells but also attenuated IgG production upon PD-1 blockade. Taken together, PD-1 blockade enhances humoral immunity. This process partially relies on more accumulation of CD4 T cells in GCs with the up-regulation of ICOS expression and the promotion of B cell terminal differentiation. The regulatory pattern of PD-1 blockade illustrated here provides a new mechanism of how immune checkpoint molecules regulating humoral immune responses.
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http://dx.doi.org/10.1016/j.intimp.2018.10.045DOI Listing
January 2019

Rapid determination of nosiheptide in feed based on dispersive SPE coupled with HPLC.

J Sep Sci 2019 Feb 11;42(3):706-715. Epub 2018 Dec 11.

National Reference Laboratory of Veterinary Drug Residues (SCAU), College of Veterinary Medicine, South China Agricultural University, Guangzhou, P. R. China.

A novel, simple, and reliable method based on high-performance liquid chromatography coupled with fluorescence detection has been developed for the determination of nosiheptide in feed. The feed samples were extracted with acetonitrile 0.1% formic acid aqueous solution and then purified via a dispersive solid-phase extraction procedure using silica gel powder as the sorbent. Using a mixture of acetonitrile and 5 mM ammonium acetate solution (containing 0.1% formic acid) as the mobile phase, good separation and peak shape were obtained for nosiheptide on a Poroshell C column (250 × 4.6 mm id, 4 μm) via the isocratic elution program. The resulting calibration curve shows high levels of linearity (r > 0.999) for nosiheptide concentrations of 50-1000 μg/L. At three spiked levels, i.e., 0.500, 2.50 and 5.00 mg/kg, the intra- and interday recoveries of nosiheptide in five types of feed ranged from 78.5-96.8 and 84.9-94.2%, respectively. The intra- and interday relative standard deviations were less than 10.8%. The limits of quantification for nosiheptide in complete feed and premixes were measured as 50 and 100 μg/kg, respectively. Compared with other common adsorbents, silica gel presents stronger recovery and purification results for feed samples during the dispersive solid-phase extraction process.
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http://dx.doi.org/10.1002/jssc.201801036DOI Listing
February 2019

Menthol facilitates dopamine-releasing effect of nicotine in rat nucleus accumbens.

Pharmacol Biochem Behav 2018 12 8;175:47-52. Epub 2018 Sep 8.

Department of Pathology, University of Mississippi Medical Center, Jackson, MS 39216, USA. Electronic address:

Menthol is a significant flavoring additive in tobacco products. Accumulating clinical evidence suggests that menthol may promote tobacco smoking and nicotine dependence. Our previous studies demonstrated that menthol enhanced nicotine reinforcement in rats. However, it is unclear whether menthol interacts with nicotine at the neurochemical level. The present study used intracranial microdialysis to examine whether and the ways in which menthol affects nicotine-induced dopamine release in rats in the nucleus accumbens core (NAc), a terminal field of brain reward circuitry. To make comparisons with our previous work that showed an enhancing effect of menthol on nicotine self-administration behavior, male Sprague-Dawley rats were first trained in 20 daily 1-h sessions to press a lever for intravenous nicotine self-administration (15 μg/kg/infusion). Dopamine levels were then measured in the right NAc using intracranial microdialysis coupled with high-performance liquid chromatography. Five minutes before microdialysis, the rats received an intraperitoneal injection of menthol (0, 1, 2.5, and 5 mg/kg), a subcutaneous injection of nicotine (0.2 mg/kg or its vehicle), or both. Menthol alone did not affect dopamine levels in dialysates, whereas nicotine alone elevated dopamine levels. Combined nicotine and menthol administration significantly increased dopamine levels compared with nicotine alone. These data indicate a facilitating effect of menthol on nicotine-induced dopamine release in the NAc. These findings shed light on our understanding of the neurobiological mechanisms that underlie the menthol-induced enhancement of nicotine reinforcement.
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http://dx.doi.org/10.1016/j.pbb.2018.09.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6240495PMC
December 2018

Analysis of Glycosylation Profiles of Serum Glycoprotein from Iron Overload Thalassemia.

Clin Lab 2018 Jul;64(7):1279-1287

Background: The aim of this study was to use a lectin microarray to detect differential glycan profiling of serous glycoprotein in iron overload thalassemia patients.

Methods: This study enrolled iron overload α/β-thalassemia patients and no iron overload α/β-thalassemia patients. Lectin microarray was used to detect the alteration of protein glycosylation. The reliability of the lectin microarray results was verified by the lectin blotting technique. Expression level of hepcidin, erythropoietin, ferritin, and transferrin were measured by western blotting. Data were analyzed using the SPSS 16.0 software.

Results: In this study, 19 differentiating lectins were screened from the iron overload α-thalassemia group, and 15 were screened from the iron overload β-thalassemia group. The agglutinin blotting technique demonstrated that the results of the Aleuria aurantia lectin (AAL), Lens culinaris agglutinin (LCA), and Wheat germ agglutinin (WGA) agglutinin affinity for serum glycoproteins were consistent with the results of the lectin microarray. In iron overload thalassemia groups, expression levels of erythropoietin and ferritin were increased, but hepcidin and transferrin were significantly reduced.

Conclusions: The differentially expressed glycoprotein database of iron overload thalassemia was successfully created, and the specific glycan patterns of serous glycoprotein might be efficient biomarkers for diagnosis or progression of iron overload thalassemia.
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http://dx.doi.org/10.7754/Clin.Lab.2018.180319DOI Listing
July 2018

[Determination of 3-methylquinoxaline-2-carboxylic acid of olaquindox marker residue in chicken muscles by liquid chromatography-tandem mass spectrometry].

Se Pu 2018 May;36(5):446-451

National Reference Laboratory of Veterinary Drug Residues(SCAU), College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.

A simple, sensitive, scientific and reproducible liquid chromatography-tandem mass spectrometric method was developed to determine 3-methylquinoxaline-2-carboxylic acid (MQCA) of olaquindox marker residue in chicken muscle tissues. The chickens were administered orally with olaquindox and used as positive samples. The approaches, enzyme, acid, and base hydrolysis, were adopted to digest MQCA in the medicated chicken muscles. The amounts of MQCA in the medicated chicken were determined and compared using different hydrolysis approaches. It was shown that the highest amount of MQCA was obtained for the base hydrolysis approach. Here, the sample was hydrolyzed with 1.0 mol/L NaOH solution, defatted with -hexane, and purified with a mixed anion-exchange solid-phase extraction cartridge. The chromatographic separation was performed on a reversed-phase C column and detected using mass spectrometry in selected reaction monitoring mode. The analyte showed good linearity in the range 1.0-100 μg/L. The correlation coefficient () was greater than 0.99. The limit of detection of the proposed method was 0.4 μg/kg. At the three spiked levels of 1.0, 5.0 and 50.0 μg/kg, the average recoveries of MQCA were in range 71.7%-82.4% obtained using external standard calibration, and in range 96.3%-103.7% for internal standard calibration, with relative standard deviations below 6.0%. The proposed method is suitable for routinely monitoring of MQCA residues in animal-derived foods.
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http://dx.doi.org/10.3724/SP.J.1123.2017.12023DOI Listing
May 2018

Quick Multi-Class Determination of Residues of Antimicrobial Veterinary Drugs in Animal Muscle by LC-MS/MS.

Molecules 2018 Jul 16;23(7). Epub 2018 Jul 16.

National Reference Laboratory of Veterinary Drug Residues (SCAU), College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.

On the basis of the highly sensitive and selective liquid chromatography-tandem mass spectrometry technique, a generic extraction solvent and a sample dilution method was developed for the residue analysis of different polar veterinary drugs known as fluoroquinolones, sulfonamides, macrolides, and tiamulin in chicken muscle. The results showed that the matrix-matched calibration curves of all 10 compounds were in an effective linear relationship (² ≥ 0.997) in the range of 0.2⁻100 μg L. At three spiking levels of 2 (5), 50, and 100 μg kg, average recoveries of analytes were between 67.1% and 96.6% with relative standard deviations of intra-day and inter-day below 20%. The limits of detection and limits of quantification of the method were in the range of 0.3⁻2.0 μg kg and 2.0⁻5.0 μg kg, respectively, which were significantly lower than their maximum residue limits. In addition, the intensity of the target analytes and its corresponding matrix effects were obviously related to the sample dilution times (matrix concentration). There were no significant differences ( > 0.05) in the average content of almost any of the analytes in medicated chickens between this method and the method in the literature for determining analytes. Lastly, the proposed method was successfully applied for the simultaneous analysis of 10 common veterinary drugs in food animal muscle tissues.
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http://dx.doi.org/10.3390/molecules23071736DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6099539PMC
July 2018

Determination of Ten Macrolide Drugs in Environmental Water Using Molecularly Imprinted Solid-Phase Extraction Coupled with Liquid Chromatography-Tandem Mass Spectrometry.

Molecules 2018 May 14;23(5). Epub 2018 May 14.

National Reference Laboratory of Veterinary Drug Residues (SCAU), College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.

With the extensive application of antibiotics in livestock, their contamination of the aquatic environment has received more attention. Molecularly imprinted polymer (MIP), as an eco-friendly and durable solid-phase extraction material, has shown great potential for the separation and enrichment of antibiotics in water. This study aims at developing a practical and economical method based on molecularly imprinted solid phase extraction (MISPE) combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) for simultaneously detecting ten macrolide drugs in different sources of water samples. The MIP was synthesized by bulk polymerization using tylosin as the template and methacrylic acid as the functional monomer. The MIP exhibited a favorable load-bearing capacity for water (>90 mL), which is more than triple that of non-molecularly imprinted polymers (NIP). The mean recoveries of macrolides at four spiked concentration levels (limit of quantification, 40, 100, and 400 ng/L) were 62.6⁻100.9%, with intra-day and inter-day relative standard deviations below 12.6%. The limit of detection and limit of quantification were 1.0⁻15.0 ng/L and 3.0⁻40.0 ng/L, respectively. Finally, the proposed method was successfully applied to the analysis of real water samples.
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http://dx.doi.org/10.3390/molecules23051172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6100474PMC
May 2018

Serum Proteomic Analysis by Tandem Mass Tags (TMT) Based Quantitative Proteomics in Gastric Cancer Patients.

Clin Lab 2018 May;64(5):855-866

Background: To use the tandem mass tags (TMT) based quantitative proteomics technique and bioinformatics method to identify potential serum diagnostic biomarkers for gastric cancer (GC).

Methods: This study enrolled GC patients and healthy control subjects. Mixed serum samples were pooled with 10 individual samples. The high-abundance proteins depleted serum proteins were collected by removing abundance albumin and immunoglobulin G (IgG). After desalting and ultrafiltration, the trypsin digested proteins were analyzed using TMT based quantitative proteomics system. The differential proteins were screened using the cutoff value of 1.2-fold change for up-regulation or down-regulation. The gene ontology (GO) was further analyzed using the UniProtKB/Swiss-Prot database. Then the differentially expressed protein ITIH4, S100A8, CD59, and COF1 were conducted using western blot.

Results: A total of 594 distinct serum proteins were identified between the GC group and the healthy controls. Forty-eight proteins were up-regulated and 57 were down-regulated using the cutoff value of 1.2-fold change. Using bioinformatics analysis, we found that the differentially expressed proteins were mainly concentrated in the extracellular exosome, extracellular region, extracellular space, and plasma membrane; their biological process activities included antigen binding, calcium ion binding, and protein homodimerization. In addition, the western blotting results showed that four differentially expressed proteins were completely coincident with the TMT quantification trend.

Conclusions: The results showed that we were able to successfully create the differentially expressed protein database of GC using TMT technology. These proteins are potential molecular markers that could help us understand the potential molecular mechanism of GC.
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http://dx.doi.org/10.7754/Clin.Lab.2018.171129DOI Listing
May 2018

Freeze-thaw approach: A practical sample preparation strategy for residue analysis of multi-class veterinary drugs in chicken muscle.

J Sep Sci 2018 Jun 25;41(11):2461-2472. Epub 2018 Apr 25.

National Reference Laboratory of Veterinary Drug Residues (SCAU), College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong, P. R. China.

Seven drugs from different classes, namely, fluoroquinolones (enrofloxacin, ciprofloxacin, sarafloxacin), sulfonamides (sulfadimidine, sulfamonomethoxine), and macrolides (tilmicosin, tylosin), were used as test compounds in chickens by oral administration, a simple extraction step after cryogenic freezing might allow the effective extraction of multi-class veterinary drug residues from minced chicken muscles by mix vortexing. On basis of the optimized freeze-thaw approach, a convenient, selective, and reproducible liquid chromatography with tandem mass spectrometry method was developed. At three spiking levels in blank chicken and medicated chicken muscles, average recoveries of the analytes were in the range of 71-106 and 63-119%, respectively. All the relative standard deviations were <20%. The limits of quantification of analytes were 0.2-5.0 ng/g. Regardless of the chicken levels, there were no significant differences (P > 0.05) in the average contents of almost any of the analytes in medicated chickens between this method and specific methods in the literature for the determination of specific analytes. Finally, the developed method was successfully extended to the monitoring of residues of 55 common veterinary drugs in food animal muscles.
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http://dx.doi.org/10.1002/jssc.201701510DOI Listing
June 2018

Sinomenine Hydrochloride Inhibits the Metastasis of Human Glioblastoma Cells by Suppressing the Expression of Matrix Metalloproteinase-2/-9 and Reversing the Endogenous and Exogenous Epithelial-Mesenchymal Transition.

Int J Mol Sci 2018 Mar 14;19(3). Epub 2018 Mar 14.

Beijing Key Laboratory of Traditional Chinese Medicine Basic Research on Prevention and Treatment of Major Diseases, Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing 100000, China.

As shown in our previous study, sinomenine hydrochloride (SH), the major bioactive alkaloid isolated from Rehd. et Wils. (Fam. ), initiates the autophagy-mediated death of human glioblastoma cells by generating reactive oxygen species and activating the autophagy-lysosome pathway. However, its effects on the migration and invasion of human glioblastoma cells have not yet been elucidated. Therefore, human glioblastoma U87 and SF767 cells were treated with SH (0.125 and 0.25 mM) for 24 h, and cell migration and invasion were assessed using scratch wound healing, migration and invasion assays. SH promoted G0/G1 phase arrest, inhibited the migration and invasion of the two cell lines, suppressed the activation of nuclear factor kappa B (NFκB) and the expression of matrix metalloproteinase (MMP)-2/-9, triggered endoplasmic reticulum (ER) stress, reversed the exogenous epithelial-mesenchymal transition (EMT) induced by the inflammatory microenvironment and the endogenous EMT. Additionally, NFκB p65 overexpression blocked the SH-mediated inhibitory effects on MMP-2/-9 expression and cell invasion. SH-induced autophagy was reduced in CCAAT/enhancer binding protein (C/EBP) homologous protein (CHOP) or autophagy-related 5 (ATG5)-silenced human glioblastoma cells and cells treated with 4-phenylbutyric acid (4-PBA) or 3-methyladenine (3-MA), as shown by the decreased levels of the microtubule-associated protein light chain 3B (LC3B)-II and autophagic vacuoles (AVs) stained with monodansylcadaverine (MDC), respectively. Moreover, knockdown of CHOP or ATG5 and treatment with 4-PBA or 3-MA abolished the SH-mediated inhibition of mesenchymal markers (vimentin, Snail and Slug) expression and cell invasion, respectively. Importantly, SH also regulated the above related pathways in nude mice. Based on these findings, SH inhibited cell proliferation by inducing cell cycle arrest, and attenuated the metastasis of U87 and SF767 cells by suppressing MMP-2/-9 expression and reversing the endogenous and exogenous EMT in vitro and/or in vivo. Thus, SH might be a new potential anti-metastasis agent for the treatment of human glioblastoma.
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http://dx.doi.org/10.3390/ijms19030844DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5877705PMC
March 2018

Simultaneous determination of eight cyclopolypeptide antibiotics in feed by high performance liquid chromatography coupled with evaporation light scattering detection.

J Chromatogr B Analyt Technol Biomed Life Sci 2018 Feb;1076:103-109

National Reference Laboratory of Veterinary Drug Residues (SCAU), College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China; Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou 510642, China. Electronic address:

A high throughput, reliable and reproducible analysis strategy based on high performance liquid chromatography combined to evaporative light scattering detector (HPLC-ELSD) was developed for simultaneous determination of eight cyclopolypeptide antibiotics including vancomycin, polymyxin B (polymyxin B1 and polymyxin B2), polymyxin E (colistin A and colistin B), teicoplanin, bacitracin A, daptomycin and virginiamycin M1 in animal Feed. Feed samples were extracted with methanol-2% formic acid aqueous solution, followed by a solid-phase extraction step using a HLB cartridge. Under the optimum chromatographic conditions and ELSD parameters, target compounds were separated well on a short column filled with biphenyl stationary phase. The method was developed in accordance with pig complete feed and then extended to detect polypeptide antibiotics in piglet premix, pig feed additive, poultry complete feed and fattening pig premix. The results showed that logarithmic calibration curves of eight analytes were linear (r > 0.99) within the concentration range of 5-200 mg mL. The developed method provided good accuracy and precision for quantification of eight polypeptides in five kinds of feeds with recoveries ranging from 72.0% to 105.4% with relative standard deviations <9.5%. The limits of detection ranged from 2 to 5 mg kg. Finally, the method was successfully applied to analyze polypeptide antibiotics in commercial feed.
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http://dx.doi.org/10.1016/j.jchromb.2018.01.020DOI Listing
February 2018

Lamin B2 binding to minichromosome maintenance complex component 7 promotes non-small cell lung carcinogenesis.

Oncotarget 2017 Dec 18;8(62):104813-104830. Epub 2017 Aug 18.

Departments of Pathology, School of Basic Medical Sciences, China Medical University, Liaoning, China.

We investigated the role of lamin B2 in non-small cell lung cancer (NSCLC). We detected higher lamin B2 expression in 20 NSCLC tumor tissues obtained from The Cancer Genome Atlas than in adjacent normal lung tissues. LMNB2-RNAi knockdown in A549 and H1299 NSCLC cells inhibited colony formation, cell proliferation and G1-S cell cycle progression while increasing apoptosis. LMNB2 overexpression had the opposite effects. Tumor xenograft experiments showed diminished tumor growth with LMNB2 knockdown H1299 cells than with controls. Yeast two-hybrid studies revealed minichromosome maintenance complex component 7 (MCM7) to be a binding partner of lamin B2, which was confirmed by co-immunoprecipitation and co-localization studies. Lamin B2 binding enhanced DNA binding and helicase activities of MCM7. Deletion analysis with MCM7-N, MCM7-M or MCM7-C mutant proteins showed that lamin B2 binds to the C-terminus of MCM7, and competes with the binding of the tumor suppressor retinoblastoma (RB) protein. Immunohistochemical analysis of 150 NSCLC patient samples revealed that both lamin B2 and MCM7 levels positively correlated with histological grade and tumor TNM stage. Moreover, high lamin B2 and MCM7 levels correlated with shorter overall survival of NSCLC patients. In sum, these results show that lamin B2 interaction with MCM7 promotes NSCLC progression.
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http://dx.doi.org/10.18632/oncotarget.20338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5739603PMC
December 2017

Renoprotective Effects of Total Glucosides from Paeony against Nephrotoxicity Induced by Total Alkaloids from .

Evid Based Complement Alternat Med 2017 22;2017:8256278. Epub 2017 Oct 22.

School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.

have been shown to have therapeutic effect in improving blood circulation, relieving rheumatic pain, and treating cancer. However, could cause severe nephrotoxicity. The present study was designed to evaluate whether treatment with total glucosides from paeony (TGP) has renoprotective effect against nephrotoxicity induced by total alkaloids from (TAS). The levels of blood urea nitrogen (BUN) and creatinine (Cr) were determined and histopathological changes were also examined to evaluate renal injury. Moreover, a HPLC-MS method was developed and validated to investigate the comparative toxicokinetics of strychnine and brucine in rats plasma after oral administration of TAS and pretreatment with TGP. Results demonstrated that the levels of BUN and Cr were significantly increased ( < 0.05) in TAS group, together with tubule epithelium cloudy swelling, degeneration, and glomerular atrophy in rats' kidneys. The TAS-induced kidney damage was alleviated after pretreatment with TGP. Besides, of strychnine and brucine were increased and of strychnine and brucine were decreased after pretreatment with TGP. The toxicokinetics study showed that pretreatment with TGP could attenuate the absorption of strychnine and brucine, as well as accelerate their elimination. These results suggest that TGP possesses renoprotective effects.
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http://dx.doi.org/10.1155/2017/8256278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5671718PMC
October 2017

Effects of menthol and its interaction with nicotine-conditioned cue on nicotine-seeking behavior in rats.

Psychopharmacology (Berl) 2017 Dec 16;234(23-24):3443-3453. Epub 2017 Sep 16.

Department of Pathology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS, 39216, USA.

Rationale: Increasing clinical evidence suggests that menthol, a significant flavoring additive in tobacco products, may contribute to smoking and nicotine dependence. Relapse to smoking behavior presents a formidable challenge for the treatment of tobacco addiction. An unresolved issue is whether the mentholation of tobacco products precipitates relapse to tobacco use in abstinent smokers.

Objectives: The present study examined the effects of menthol on the perseverance and relapse of nicotine-seeking behavior in rats.

Methods: Male Sprague-Dawley rats were trained to press a lever for intravenous nicotine self-administration (0.03 mg/kg/infusion) under a fixed-ratio five schedule of reinforcement. Each nicotine infusion was signaled by the presentation of a sensory stimulus that was established as a discrete nicotine-conditioned cue. Five minutes prior to the sessions, the rats received an intraperitoneal injection of menthol (0.1 mg/kg) or vehicle. In the subsequent extinction test sessions, nicotine was unavailable with or without menthol and/or the nicotine-conditioned cue. The reinstatement tests were performed the following day after the extinction criterion was met. Menthol was also tested on food-seeking responses. In a subset of nicotine-trained rats, a transient receptor potential melastatin 8 (TRPM8) antagonist RQ-00203078 was given prior to menthol administration.

Results: Continued administration of menthol sustained responses on the previously active and nicotine-reinforced lever in the extinction tests. The readministration of menthol after extinction reinstated active lever responses. In both the extinction and the reinstatement tests, a combination of pre-session menthol administration and cue representation during the session produced a more robust behavioral effect than either menthol or the cue alone. No such effects of menthol was observed in food trained rats. RQ-00203078 did not change menthol effect on nicotine seeking.

Conclusion: These data demonstrated that menthol specifically sustained and reinstated nicotine-seeking behavior, and this effect was independent of TRPM8 activity. These findings suggest that menthol in most tobacco products, even not menthol labeled, may contribute to the perseverance of and relapse to tobacco-seeking behavior.
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http://dx.doi.org/10.1007/s00213-017-4736-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5693741PMC
December 2017

Value of Red Cell Distribution Width in Assessing the Severity of Hepatitis B Virus-Related Decompensated Cirrhosis.

Clin Lab 2017 Sep;63(9):1467-1474

Background: Hepatitis B virus infection is the main reason for liver cirrhosis in China. Thus, evaluating the disease severity of hepatitis B-related decompensated cirrhosis (HBV-DeCi) is very important. The red cell distribution width (RDW) is thought to be correlated with the severity of various diseases. The purpose of this investigation is to verify whether RDW can estimate the disease severity of HBV-DeCi.

Methods: This retrospective study included 172 subjects who had been diagnosed with HBV-DeCi. They were categorized into three groups on the basis of their RDW values. Receiver operating curve (ROC) was used to estimate the severity predictive performances and binary logistic regression was used to assess the independent variable predicting the severity of liver disease.

Results: The RDW values were evidently increased in the HBV-DeCi patients in comparison with the healthy controls (18.00% ± 0.04 vs. 13.19% ± 0.74, p < 0.001). There was also a significant difference in the model for endstage liver disease score of the three different RDW groups of A, B and C (13.2 ± 4.6, 16.0 ± 9.0, and 18.8 ± 6.5, p = 0.002). The RDW was an independent risk factor of the severity of HBV-DeCi. The cutoff level for RDW was > 14.0%, where the sensitivity and specificity were 90.7%, 100.0%, respectively, and the area under the curve (AUC) of ROC was 0.969. For a combination of RDW and MELD score, the AUC was 0.997, and the sensitivity and specificity were 98.3% and 99.1%, respectively.

Conclusions: The RDW is a simple biomarker that may play an important role in predicting the severity of HBVDeCi.
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http://dx.doi.org/10.7754/Clin.Lab.2017.170331DOI Listing
September 2017

Increased Red Blood Cell Volume Distribution Width: Important Clinical Implications in Predicting Gastric Diseases.

Clin Lab 2017 Jul;63(7):1199-1206

Background: The red blood cell distribution width (RDW) is a blood analyzer marker showing the peripheral blood erythrocyte volume heterogeneity parameters. It is a normal diagnosis index of many diseases. This study was performed to evaluate the relationship between the RDW and gastric diseases.

Methods: A total of 189 patients with GC, 68 patients with gastric ulcers, 92 patients with chronic gastritis, and 157 healthy controls were enrolled in this study. Each patient's RDW and other biomarkers were recorded. All of the statistical analyses and comparisons between each group were determined using SPSS16.0 software. The statistical significance level was set to a p-value < 0.05.

Results: The RDW was significantly higher in those patients with gastric diseases when compared to the control group (p < 0.05). In addition, the RDW was independently correlated with the presence of GC and gastric ulcers. Significantly positive correlations between the RDW, platelets, and platelet distribution width (PDW) were observed in those patients with GC and gastric ulcers, although there were negative correlations with the red blood cells (RBCs), hemoglobin, and mean corpuscular volume (MCV) (p < 0.05). In the chronic gastritis group, elevated RDW values were closely associated with the hemoglobin, platelet, and MCV values (p < 0.05). The specificities of the gastric diseases groups were greater than 90%.

Conclusions: In cases of gastric diseases, the RDW values were increased and were associated with several laboratory parameters. These finding may have important clinical implications in predicting gastric diseases.
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http://dx.doi.org/10.7754/Clin.Lab.2017.170115DOI Listing
July 2017
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