Publications by authors named "Xiaona Zhao"

51 Publications

Label-Free Probing of Molecule Binding Kinetics Using Single-Particle Interferometric Imaging.

Anal Chem 2021 06 24;93(22):7965-7969. Epub 2021 May 24.

Department of Applied Chemistry, University of Science and Technology of China, Hefei 230026, China.

Probing molecular interactions is critical for screening drugs, detecting pollutants, and understanding biological processes at the molecular level, but these interactions are difficult to detect, especially for small molecules. A label-free optical imaging technology that can detect molecule binding kinetics is presented, in which free-moving particles are driven into oscillations with an alternating electrical field and the interferometric scattering patterns of the particles are imaged via an optical imaging method. By tracking the charge-sensitive variations in the oscillation amplitude with sub-nanometer precision, the small molecules and metal ions binding to the surface as well as protein-protein binding kinetics were measured. The capability of the label-free measurement of molecular interactions can provide a promising platform for screening small-molecule drugs, probing conformational changes in proteins, and detecting environmental pollutants.
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http://dx.doi.org/10.1021/acs.analchem.1c00828DOI Listing
June 2021

Evaluation of the differences between biofilm and planktonic Brucella abortus via metabolomics and proteomics.

Funct Integr Genomics 2021 Jul 19;21(3-4):421-433. Epub 2021 May 19.

MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, 1 Weigang, Xuanwu, Nanjing, Jiangsu Province, 210095, People's Republic of China.

This study analyzed the difference between biofilm and planktonic Brucella abortus using metabolomics and proteomics. Brucella abortus was cultured in different media to induce Brucella abortus biofilm formation and planktonic cells, followed by metabolomics and proteomics analyses for these two samples. Significant differential metabolites were identified, followed by KEGG pathway analysis. Differentially expressed proteins were identified, followed by subcellular localization, GO annotation, and KEGG pathway enrichment. Additionally, a correlation analysis of metabolomics and proteomics was performed. Metabolomics analysis showed 7682 positive and 4433 negative metabolites, including 188 positive and 117 negative significant differential metabolites. These differential metabolites were enriched in fatty acid/unsaturated fatty acid biosynthesis and linoleic acid metabolism. Proteomics analysis revealed 1759 proteins, including 486 differentially expressed proteins, which were enriched in various metabolic and degradation-related pathways. Subcellular localization showed that 74.3% of the differential proteins were cytoplasmic proteins. Correlation analysis showed that 1-palmitoyl-2-oleoyl-phosphatidylglycerol had the most significant correlations with proteins, followed by cytosine. Both metabolites correlated with the protein Q57EI7 (RbsB-1, ribose ABC transporter). One common pathway, fatty acid biosynthesis, was identified by both proteomics and metabolomics analyses that involved the metabolites, oleic acid, and protein Q57DK3 (biotin carboxylase). There were metabolomic and proteomic differences between Brucella abortus biofilm and planktonic cells, and these results provide novel insights into the biofilm-forming process of Brucella abortus.
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http://dx.doi.org/10.1007/s10142-021-00788-7DOI Listing
July 2021

Inflammatory injury and mitophagy of the brain in chicken exposed to Cr(VI).

Environ Sci Pollut Res Int 2021 Apr 4. Epub 2021 Apr 4.

College of Veterinary Medicine, Shandong Agricultural University, Tai`an, 271018, Shandong, China.

The aim of this study is to determine whether Cr(VI) can induce inflammatory injury in chicken brain and influence mitophagy and related mechanisms. A total of 120 hyline brown chickens (1 day old, 20±3g) were selected and randomly divided into four groups and given different doses of Cr(VI) (0, 10, 30, and 50 mg/kg) every day at 45 days. Results showed that excessive intake of Cr(VI) led to increased tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) levels and decreased interferon-gamma (IF-γ) level. Cr(VI) increased the production of mitochondrial reactive oxygen species (ROS) in chicken brain cells, causing the decline of mitochondrial membrane potential (MMP) and formation of autophagosomes for mitophagy. In addition, Cr(VI) promoted the translocation of Parkin to the mitochondrial outer membrane, increased LC3-II protein level, and inhibited p62 and TOM20 protein expression. In conclusion, excessive Cr(VI) intake can induce inflammatory injury and mitophagy in chicken brain.
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http://dx.doi.org/10.1007/s11356-021-13675-2DOI Listing
April 2021

The role of ATF6 in Cr(VI)-induced apoptosis in DF-1 cells.

J Hazard Mater 2021 05 19;410:124607. Epub 2020 Nov 19.

College of Veterinary Medicine, Shandong Agricultural University, Tai'an, Shandong 271018, China. Electronic address:

Hexavalent chromium (Cr(VI)) is a common heavy metal pollutant in environment and has been proved possessing the cytotoxicity. In this study, we aimed to investigate the role of activating transcription factor 6 (ATF-6) in apoptosis of chicken embryo fibroblasts cell line (DF-1) induced by Cr(VI). Firstly, DF-1 cells were exposed to Cr(VI) to establish the cytotoxicity model, then the cell apoptosis and ATF-6 protein level were analyzed. By silencing ATF-6 gene, changes of the apoptosis rate and apoptotic proteins were examined. To further explore the regulatory mechanism of ATF-6, endoplasmic reticulum (ER) stress, mitochondrial function, reactive oxygen species (ROS) level, as well as the related pathway were evaluated. Results showed that Cr(VI) can result in DF-1 cell apoptosis, along with mitochondrial membrane potential (MMP) reducing and ER stress. Meanwhile, ATF-6 silencing lowered the apoptosis rate and ER stress level, showing with the decrease of XBP-1, PERK, GRP78, Caspase-12, Cleaved Caspase-3 and the increase of Bcl-2. Further analysis found that ATF-6 silencing down-regulated ROS and caused MMP loss, suggesting that ATF-6 silencing inhibited Cr(VI)-induced mitochondrial damage. In conclusion, this study indicate that ATF-6 plays an important regulatory role in Cr(VI)-induced DF-1 cell apoptosis through the ER stress and mitochondrial pathway.
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http://dx.doi.org/10.1016/j.jhazmat.2020.124607DOI Listing
May 2021

NAD administration decreases microvascular damage following cardiac ischemia/reperfusion by restoring autophagic flux.

Basic Res Cardiol 2020 08 10;115(5):57. Epub 2020 Aug 10.

Department of Cardiology, Huadong Hospital, Fudan University, 221 West Yanan Road, Shanghai, 200040, China.

Microvascular damage is a key pathological change in myocardial ischemia/reperfusion (I/R) injury. Using a rat model of myocardial I/R, our current study has provided the first evidence that nicotinamide adenine dinucleotide (NAD) administration can significantly attenuate myocardial I/R-induced microvascular damage, including reduced regional blood perfusion, decreased microvessel density and integrity, and coronary microvascular endothelial cells (CMECs) injury. In studies with primary cultured CMECs under hypoxia/reoxygenation (HR) and a rat model of I/R, our results suggested that the protective effect of NAD on CMECs exposed to HR or I/R is at least partially mediated by the NAD-induced restoration of autophagic flux, especially lysosomal autophagy: NAD treatment markedly induced transcription factor EB (TFEB) activation and attenuated lysosomal dysfunction in the I/R or HR-exposed cells. Collectively, our study has provided the first in vivo and in vitro evidence that NAD significantly rescued the impaired autophagic flux and cell apoptosis that was induced by I/R in rat CMECs, which is mediated in part through the action of TFEB-mediated lysosomal autophagy.
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http://dx.doi.org/10.1007/s00395-020-0817-zDOI Listing
August 2020

Platycodon grandifloras polysaccharides inhibit mitophagy injury induced by Cr (VI) in DF-1 cells.

Ecotoxicol Environ Saf 2020 Oct 25;202:110901. Epub 2020 Jun 25.

College of Veterinary Medicine, Shandong Agricultural University, Tai'an, Shandong, 271018, China. Electronic address:

This study aimed to investigate the role of Platycodon grandiflorus polysaccharide (PGPS) in chromium (VI)-induced autophagy in a chicken embryo fibroblast cell lines (DF-1 cells). DF-1 cells were exposed to Cr (VI), PGPS, and Cr (VI) + PGPS, and their effects on cell viability, reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and autophagy-related proteins were examined. The results showed that the cell viability was reduced after Cr (VI) treatment, and 3-MA, CsA or PGPS suppressed this decrease. Cr (VI) treatment increased the ROS levels and decreased the MMP, thereby enhancing the expression of mitochondrial autophagy marker proteins (PINK1, Parkin, and LC3-II), inhibiting mitophagy autophagy protein TOMM20 expression, and promoting the degradation of autophagy-related marker p62. These changes led to exceeding mitochondrial autophagy and cell trauma and could be mitigated by PGPS. Overall, our research showed that Cr (VI) can induce exceeding mitochondrial autophagy in DF-1 cells, whereas PGPS can improve Cr (VI)-induced mitochondrial autophagy by inhibiting ROS and restoring MMP.
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http://dx.doi.org/10.1016/j.ecoenv.2020.110901DOI Listing
October 2020

Mitophagy Induced by Mitochondrial Function Damage in Chicken Kidney Exposed to Cr(VI).

Biol Trace Elem Res 2021 Feb 21;199(2):703-711. Epub 2020 May 21.

College of Veterinary Medicine, Shandong Agricultural University, Taiàn, 271018, Shandong, China.

Cr(VI) is a heavy metal environmental pollutant and carcinogen. Excessive Cr(VI) exposure injures kidneys. This study aimed to investigate mitophagy induced by mitochondrial function damage in chicken kidney exposed to Cr(VI). To explore the mechanism involved, we randomly divided 40 one-day-old Hy-line Brown cockerels into four groups, with each group exposed to different concentrations of Cr(VI), i.e., 0, 10, 30 and 50 mg kg, which were orally administered daily for 45 days. Excessive Cr(VI) increased tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and chemokine (C-X-C motif) ligand 1(CXCL1) expression and decreased Ca-adenosine triphosphatase (Ca-ATPase), Mg-ATPase and Na/k-ATPase activities in chicken kidney. Furthermore, Cr(VI) significantly increased reactive oxygen species (ROS) production and induced mitochondrial membrane potential (MMP) collapse and typical autophagosome formation. With the increase of Cr(VI) concentration, the Parkin translocation, value of LC3-II increased and decreased the content of p62/SQSTM1 and the translocase of outer mitochondrial membrane 20 (TOMM20). In summary, our findings explicated that mitochondrial function damage and mitophagy-related indicators were related to Cr(VI) concentration in chicken kidney.
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http://dx.doi.org/10.1007/s12011-020-02176-xDOI Listing
February 2021

Coronary Arteritis and Periaortitis in IgG4-Related Disease.

Can J Cardiol 2020 04 30;36(4):589.e5-589.e7. Epub 2019 Nov 30.

Department of Cardiology, Huadong Hospital, Fudan University, 221 West Yanan Road, Shanghai, 200040, China; Shanghai Key Laboratory of Clinical Geriatric Medicine, Shanghai, 200040, China. Electronic address:

We report an interesting case of coronary arteritis and periaortitis in a 62-year-old man with a history of biopsy-proven IgG4-related pulmonary disease. After 2 years of immune-suppressive therapy, the perivascular tissue surrounding all coronary arteries and the abdominal aorta was significantly attenuated, except that the luminal stenosis was aggravated to 70% in the left anterior descending coronary artery. Treatment with aspirin, atorvastatin, and ezetimibe was added. The patient was discharged under strict lesion surveillance at follow-up.
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http://dx.doi.org/10.1016/j.cjca.2019.11.028DOI Listing
April 2020

Protective effects of Platycodon grandiflorus polysaccharides against apoptosis induced by carbonyl cyanide 3-chlorophenylhydrazone in 3D4/21 cells.

Int J Biol Macromol 2019 Dec 12;141:1220-1227. Epub 2019 Sep 12.

Research Center for Animal Disease Control Engineering, Shandong Agricultural University, Tai'an, Shandong 271018, China. Electronic address:

This study aimed to investigate the potential protective effects of Platycodon grandiflorus polysaccharide (PGPS) on carbonyl cyanide 3-chlorophenylhydrazone (CCCP)-induced mitochondrial apoptosis in 3D4/21 cells. Apoptosis-related indicators such as cell viability, apoptosis rate, mitochondrial membrane potential (MMP), and apoptosis-related protein were examined. Results indicated that PGPS can inhibit CCCP-induced cell damage, with cell-survival rate reaching 81% and apoptotic rate decreasing to 23%. Nuclear deformation was also significantly reduced in the PGPS group, and changes in MMP were inhibited by PGPS. Further analyses showed that the protein expression of Caspase-9 and Bcl-2 increased and the expression of cleaved Caspase-3 decreased, indicating that PGPS significantly inhibited the CCCP-induced change in apoptotic protein expression. All these results suggested that PGPS can antagonize 3D4/21 cell apoptosis by restoring MMP, protecting the integrity of nuclear morphology, and increasing Bcl-2 expression.
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http://dx.doi.org/10.1016/j.ijbiomac.2019.09.086DOI Listing
December 2019

Effects of Cr(VI) exposure on electrocardiogram, myocardial enzyme parameters, inflammatory factors, oxidative kinase, and ATPase of the heart in Chinese rural dogs.

Environ Sci Pollut Res Int 2019 Oct 22;26(29):30444-30451. Epub 2019 Aug 22.

College of Veterinary Medicine, Shandong Agricultural University, Tai'an, 271018, China.

Heavily chromium-polluted areas, where people are prohibited from entering, are paradises for stray dogs. In this study, stray dogs were used to study the effects of chromium exposure on the heart of dogs in severely Cr(VI)-contaminated rural areas of China. The dogs were given water (control), low dose (L, 0.92 mg/kg), medium dose (M, 1.15 mg/kg), and high dose (H, 1.38 mg/kg) of Cr(VI). The changes of electrocardiogram (ECG), myocardial enzyme parameters, inflammatory factors, oxidative kinase, and ATPase were measured to determine the toxicity of chromium on the heart of dogs. Results showed that the ST segment of ECG increased significantly, and the amplitude of T wave increased in the experimental group. The myocardial enzyme (CK-MB, AST, CK, and LDH) content in groups M and H increased significantly over time. The values of CAT, T-SOD, IL-10, and ATPase (K-Na-ATPase and Ca-Mg-ATPase) decreased with the increase of Cr(VI) dose, and the content of MDA, IL-1β, IL-8, and TNF-α increased with the increase of Cr(VI) dose. Our study suggested that the heart of Chinese rural dog was damaged by Cr(VI), and Cr(VI) could cause oxidative damage and alteration of ATPase content in dogs.
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http://dx.doi.org/10.1007/s11356-019-06253-0DOI Listing
October 2019

Identification of Nanoparticles via Plasmonic Scattering Interferometry.

Angew Chem Int Ed Engl 2019 03 19;58(13):4217-4220. Epub 2019 Feb 19.

CAS Key Laboratory of Urban Pollutant Conversion, Department of Applied Chemistry, University of Science & Technology of China, Hefei, 230026, China.

The development of optical imaging techniques has led to significant advancements in single-nanoparticle tracking and analysis, but these techniques are incapable of label-free selective nanoparticle recognition. A label-free plasmonic imaging technology that is able to identify different kinds of nanoparticles in water is now presented. It quantifies the plasmonic interferometric scattering patterns of nanoparticles and establishes relationships among the refractive index, particle size, and pattern both numerically and experimentally. Using this approach, metallic and metallic oxide particles with different radii were distinguished without any calibration. The ability to optically identify and size different kinds of nanoparticles can provide a promising platform for investigating nanoparticles in complex environments to facilitate nanoscience studies, such as single-nanoparticle catalysis and nanoparticle-based drug delivery.
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http://dx.doi.org/10.1002/anie.201813567DOI Listing
March 2019

Riboflavin attenuates myocardial injury via LSD1-mediated crosstalk between phospholipid metabolism and histone methylation in mice with experimental myocardial infarction.

J Mol Cell Cardiol 2018 02 8;115:115-129. Epub 2018 Jan 8.

Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China. Electronic address:

The underlying mechanisms responsible for the cardioprotective effects of riboflavin remain elusive. Current study tested the hypothesis that riboflavin protects injured myocardium via epigenetic modification of LSD1. Here we showed that myocardial injury was attenuated and cardiac function was improved in riboflavin-treated mice with experimental myocardial infarction (MI), while these protective effects of riboflavin could be partly blocked by cotreatment with LSD1 inhibitor. Riboflavin also reduced apoptosis in hypoxic (1% oxygen) H9C2 cell lines. Results of ChIP-seq for H9C2 cells showed that riboflavin activated LSD1, as verified by decreased H3K4me2 levels of target genes. Subsequent LEGO bioinformatics analysis indicated that phospholipid metabolism genes Lpcat2 and Pld1 served as the potential target genes responsible for the LSD1 mediated protective effects. Overexpressions of Lpcat2 and Pld1 aggravated hypoxic injury in H9C2 cells, while these detrimental effects could be attenuated by overexpression of LSD1. We thus propose that riboflavin alleviates myocardial hypoxic/ischemic injury by activating LSD1 cellular activity and modulating the expression of phospholipid metabolism genes. LSD1-mediated crosstalk between phospholipid metabolism and histone methylation might thus be an important mechanism for the cardioprotective effects of riboflavin.
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http://dx.doi.org/10.1016/j.yjmcc.2018.01.006DOI Listing
February 2018

Analysis of molecular evolution of nucleocapsid protein in Newcastle disease virus.

Oncotarget 2017 Nov 28;8(57):97127-97136. Epub 2017 Sep 28.

College of Animal Medicine and Veterinary Medicine, Shandong Agricultural University, Tai'an 271018, PR China.

The present study investigated the molecular evolution of nucleocapsid protein (NP) in different Newcastle disease virus (NDV) genotypes. The evolutionary timescale and rate were estimated using the Bayesian Markov chain Monte Carlo (MCMC) method. The p-distance, Bayesian skyline plot (BSP), and positively selected sites were also analyzed. The MCMC tree indicated that NDV diverged about 250 years ago with a rapid evolution rate (1.059 × 10 substitutions/site/year) and that different NDV genotypes formed three lineages. The p-distance results reflected the great genetic diversity of NDV. BSP analysis suggested that the effective population size of NDV has been increasing since 2000 and that the basic reproductive number (R) of NDV ranged from 1.003 to 1.006. The abundance of negatively selected sites in the NP and the mean dN/dS value of 0.07 indicated that the NP of NDV may have undergone purifying selection. However, the predicted positively selected site at position 370 was located in the known effective epitopic region of the NP. In conclusion, although NDV evolved at a high rate and showed great genetic diversity, the structure and function of the NP had been well conserved. However, R>1 suggests that NDV might have been causing an epidemic since the time of radiation.
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http://dx.doi.org/10.18632/oncotarget.21373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5722550PMC
November 2017

Effects of Polysaccharides from Platycodon grandiflorum on Immunity-Enhancing Activity In Vitro.

Molecules 2017 Nov 7;22(11). Epub 2017 Nov 7.

College of Animal Medicine and Veterinary Medicine, Shandong Agricultural University, Tai'an 271018, China.

The study is aimed at investigating the immunoenhancement activity of polysaccharides from polysaccharides (PGPSs) in vitro. In this study, some research on lymphocyte proliferation, cell cycle, and the levels of CD4⁺ and CD8⁺ T cells were performed. Four different concentrations of PGPSs (PGPS, PGPS, PGPS, and PGPS) were harvested and added to peripheral blood T lymphocytes. We observed significant increases in T lymphocyte proliferation at PGPS groups individually or synergistically with phytohemagglutinin (PHA) at most concentrations, and their lymphocyte proliferation rates were the highest. The active sites of PGPS and PGPS were subsequently chosen. Then, we utilized flow cytometry to determine lymphocyte cell cycle distribution and levels of CD4⁺ and CD8⁺ T cells. At most time points, PGPS could facilitate lymphocyte cell cycle progression from the G0/G1 phase to the S and G2/M phases and, simultaneously, increase the levels of CD4⁺ and CD8⁺ T cells. These results indicate that PGPS enhances the immune functions, suggesting that PGPS could be a potential immunopotentiator for further in vivo and clinical trial experiments.
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http://dx.doi.org/10.3390/molecules22111918DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6150289PMC
November 2017

Novel idiopathic DCM-related variants localised in DI-S4 predispose electrical disorders by reducing peak sodium current density.

J Med Genet 2017 11 4;54(11):762-770. Epub 2017 Aug 4.

Shanghai Institute of Cardiovascular Disease, Zhongshan Hospital, Fudan University, Shanghai, China.

Background: Variants of , encoding cardiac sodium channel, have been linked to the development of dilated cardiomyopathy (DCM). We aimed to explore novel variants in patients with idiopathic DCM (iDCM) and to identify the distribute characteristics and pathological mechanisms as well as clinical phenotypes associated with the variants in patients with iDCM.

Methods: exons sequencing was performed inpatients with iDCM (n=90) and two control cohorts (arrhythmias group, n=90, and healthy group, n=195). Clinical characteristics were compared between carriers and non-carriers. We then generated a novel heterozygous knock-in (KI) mouse by homologous recombination. Cardiac function, electrical parameters and histological characteristics were examined at basal or stimulating condition.

Results: We found three novel non-synonymous variants associated with iDCM, including c.674G>A, c.677C>T, and c.4340T>A. The newly defined iDCM-related variants mainly located in the S4 segment of domain I (DI-S4). Incidence of atrioventricular block was significantly higher in mutant patients with iDCM than in non-carriers. Structural injuries were absent at both basal and stress condition in KI mice carrying c.674G>A (R225Q); however, this variant significantly prolonged PR intervals at baseline without affecting other ECG parameters, which was linked to decreased peak sodium current density in KI cardiomyocytes. Histological analysis of the atrioventricular node did not show any evidences of cell damages.

Conclusion: Our results suggest that the iDCM-related variants in the DI-S4 could predispose electrical disorders by reducing peak sodium current density.
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http://dx.doi.org/10.1136/jmedgenet-2017-104780DOI Listing
November 2017

Analysis of immunostimulatory activity of polysaccharide extracted from Yu-Ping-Feng in vitro and in vivo.

Biomed Pharmacother 2017 Sep 17;93:146-155. Epub 2017 Jun 17.

College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai'an 271018, PR China. Electronic address:

As a traditional Chinese multiherbal formula, Yu-Ping-Feng (YPF) is frequently used to treat cold, flu and inflammation-associated diseases. We aimed to evaluate the immunostimulatory effects of polysaccharide isolated from YPF (YPF-PS) in vitro and in vivo. In in vitro experiment, macrophage cell proliferation, phagocytosis rate, cytokine and costimulatory molecule release, T lymphocyte proliferation, cell cycle distribution, CD4 and CD8 T cell percentages were determined. To investigate the in vivo effects of YPF-PS treatment, different doses YPF-PS were administered to chicken vaccinated against Newcastle disease. The immune organ index, lymphocyte proliferation, antibody titer, cell cycle distribution, and the cell percentage of CD4 and CD8 were assessed. In vitro results indicated that YPF-PS at 15.62μgmL could increase the LPS-induced macrophage cell proliferation and phagocytosis rate significantly. The levels of cytokine (nitric oxide, tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, and interferon beta) and costimulatory molecules (CD80 and CD86) were also considerably enhanced. Moreover, YPF-PS could significantly enhance T lymphocyte proliferation individually or synergistically with phytohemagglutinin. It promoted lymphocyte entry into S and G2/M phases and increased the percentages of CD4 and CD8 T cells effectively. In addition, in vivo experiments showed that YPF-PS could enhance serum HI antibody titer. The results about T lymphocyte proliferation, cell cycle distribution, CD4 and CD8 cell percentages in chickens were also confirmed. YPF-PS has efficacious immunomodulatory properties and could be used as a new potential immune stimulator for food and medical purposes.
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http://dx.doi.org/10.1016/j.biopha.2017.05.138DOI Listing
September 2017

Mitochondrial aldehyde dehydrogenase-2 deficiency compromises therapeutic effect of ALDH bright cell on peripheral ischemia.

Redox Biol 2017 10 29;13:196-206. Epub 2017 May 29.

Institute of Biomedical Science, Fudan University, Shanghai 200032, China; Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Shanghai 200032, China. Electronic address:

The autologous ALDH bright (ALDH) cell therapy for ischemic injury is clinically safe and effective, while the underlying mechanism remains elusive. Here, we demonstrated that the glycolysis dominant metabolism of ALDH cells is permissive to restore blood flow in an ischemic hind limb model compared with bone marrow mononuclear cells (BMNCs). PCR array analysis showed overtly elevated Aldh2 expression of ALDH cells following hypoxic challenge. Notably, ALDH cells therapy induced blood flow recovery in this model was reduced in case of ALDH2 deficiency. Moreover, significantly reduced glycolysis flux and increased reactive oxygen species (ROS) levels were detected in ALDH cell from Aldh2-/- mice. Compromised effect on blood flow recovery was also noticed post transplanting the human ALDH cell from ALDH2 deficient patients (GA or AA genotypes) in this ischemic hindlimb mice model. Taken together, our findings illustrate the indispensable role of ALDH2 in maintaining glycolysis dominant metabolism of ALDH cell and advocate that patient's Aldh2 genotype is a prerequisite for the efficacy of ALDH cell therapy for peripheral ischemia.
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http://dx.doi.org/10.1016/j.redox.2017.05.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5458766PMC
October 2017

Characterization of Chinese Porcine Epidemic Diarrhea Virus with Novel Insertions and Deletions in Genome.

Sci Rep 2017 03 9;7:44209. Epub 2017 Mar 9.

Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Key Laboratory of Veterinary Biological Engineering and Technology, Ministry of Agriculture, Nanjing 210014, China.

Outbreaks of porcine epidemic diarrhoea virus (PEDV) have caused great economic losses to the global pig industry. PEDV strains with variants in the spike (S) gene have been reported in several countries. To better understand the molecular epidemiology and genetic diversity of PEDV field isolates, in this study, we characterised the complete genome sequence of a novel PEDV variant JSCZ1601 from a outbreak in China in 2016. The PEDV isolate was 28,033 nucleotides (nt) in length without the polyadenylated sequences. Phylogenetic analysis based on the full-length genome sequence of JSCZ1601 grouped it with the pandemic variants determined post-2010 into group 2 (G2). However, the S gene of JSCZ1601 formed a new subgroup separated from the subgroups containing the other G2 strains. Comparative analysis of the amino acids encoded by the S genes revealed the N-terminal of the deduced JSCZ1601 S protein had a novel two-amino-acid deletion (N58 and S59) compared with all identified genogroups. Further, compared with the reference strains, a 'G' insertion was detected in the 5' terminal of the 5'UTR of the JSCZ1601. The animal experiment revealed that this strain was high pathogenic to neonatal pigs. Taken together, a PEDV strain with the new molecular characterizations and phylogenies was found in mainland China. It is necessary to strengthen the monitoring of PEDV variations.
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http://dx.doi.org/10.1038/srep44209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5343579PMC
March 2017

Solvothermal-assisted synthesis of self-assembling TiO nanorods on large graphitic carbon nitride sheets with their anti-recombination in the photocatalytic removal of Cr(vi) and rhodamine B under visible light irradiation.

Nanoscale 2017 Mar;9(9):3231-3245

Department of Physics and Key Laboratory of Artificial Micro- and Nano-structures of Ministry of Education, Wuhan University, Wuhan 430072, P.R. China.

TiO-based nanorods (TNRs) were self-assembled on large graphitic carbon nitride (g-CN) sheets via the solvothermal-assisted route. The results demonstrated that the effective anchoring of TNRs (a side length of ca. 200-300 nm) was highly dispersed on the surface of whole g-CN sheets. The shift in the Ti 2p XPS core level spectrum indicated an increase in the net positive charge of the Ti ions, ensuring the formation of an interface between TNRs and g-CN. The charge transferred from g-CN sheets to TNRs effectively prevented the recombination of excited charges, which is consistent with the significant quenching of PL. The extent of visible-light-sensitive photocatalytic (PC) activity was evaluated by the removal of potassium dichromate (Cr(vi)) or the degradation of rhodamine B (RhB). The photocatalytic removal of Cr(vi) using RhB was effectively improved. The synergistic effect between the removal of Cr(vi) and degradation of RhB was revealed by multiple utilization of TNRs/g-CN for PC activity. The effective suppression of the recombination of photo-induced charges and the absorption of RhB was responsible for the enhancement in the PC activity. An alternate mechanism for enhanced visible-light photocatalytic activity was also considered.
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http://dx.doi.org/10.1039/c6nr09137gDOI Listing
March 2017

Characterization of polysaccharides extracted from Platycodon grandiflorus (Jacq.) A.DC. affecting activation of chicken peritoneal macrophages.

Int J Biol Macromol 2017 Mar 2;96:775-785. Epub 2017 Jan 2.

College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai'an 271018, PR China. Electronic address:

Polysaccharides were isolated from Platycodon grandiflorus (Jacq.) A.DC. (PG) and the effects of three polysaccharides (PGPS, PGPS, PGPS) on their immunological activities were studied. The structure identification of PGPSs was assessed using physicochemical and spectral methods. Results showed that PGPS(2.67×10Da) compared to PGPS(1.01×10Da) and PGPS(1.12×10Da) has relatively higher average molecular weight(Mw) at the first peak with a narrower molecular weight distribution and all consisted of glucose, mannose, arabinose, galactose, xylose and rhamnose in different mass percentages. PGPS and PGPS linked mainly by 1,3-and 1,6-β-d-Galp residues. The immunological efficacy of PGPSs was performed on chicken peritoneal macrophages. Results showed that PGPS significantly increased phagocytic rates, proliferation and NO production, stimulated macrophages to produce cytokines, including TNF-α, IL-1β and IL-6 as well as stimulated macrophages to express the maturation markers CD80 and CD86. These findings suggest that PGPS exerted significant immunological activity and might be associated with special characters.
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http://dx.doi.org/10.1016/j.ijbiomac.2016.12.077DOI Listing
March 2017

Virulence in Newcastle disease virus: A genotyping and molecular evolution spectrum perspective.

Res Vet Sci 2017 Apr 7;111:49-54. Epub 2016 Dec 7.

College of Veterinary Medicine, Shandong Agricultural University, Tai'an 271018, China. Electronic address:

In our research, the molecular evolutions of NDV F and HN genes were analyzed. The phylogenetic analyses of NDV sequences indicated that NDV could be divided into two genotypes: Class I (lentogenic strains) and Class II (velogenic or mesogenic strains). Each genotype possesses high gene homology. Furthermore, the selected pressure analysis showed that the dN/dS of velogenic, mesogenic NDV strains F gene was significantly high and the ω(dN/dS) is 1.1725>1. These results imply that mutations in velogenic, mesogenic NDV F gene are favored by positive natural selection and it has acted to diversify NDV virulence at the nucleotide and amino acid level. We estimated that the subsequent rapid adaptation of the Newcastle disease virus to chickens were likely dependent on a high rate of mutation and the positive selection of mutations in the major F gene.
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http://dx.doi.org/10.1016/j.rvsc.2016.12.001DOI Listing
April 2017

Aldehyde dehydrogenase 2 deficiency negates chronic low-to-moderate alcohol consumption-induced cardioprotecion possibly via ROS-dependent apoptosis and RIP1/RIP3/MLKL-mediated necroptosis.

Biochim Biophys Acta Mol Basis Dis 2017 08 11;1863(8):1912-1918. Epub 2016 Nov 11.

Shanghai Institute of Cardiovascular Disease, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Institute of Biomedical Science, Fudan University, Shanghai 200032, China. Electronic address:

Previous studies evidenced the beneficial effects of low-to-moderate alcohol consumption on cardiovascular system by activation of mitochondrial aldehyde dehydrogenase 2 (ALDH2), a key enzyme metabolizing acetaldehyde to innocuous acetic acid, in diabetic mice. It remains questionable whether people with inactive ALDH2 would also benefit from the drinking habit. Present study was therefore designed to examine the influence of ALDH2 deficiency on low-to-moderate alcohol consumption related myocardial alternations. Wildtype (WT) and ALDH2 knockout (KO) mice were exposed to low-to-moderate alcohol (EtOH) challenge for 6weeks. Cardiac function and cell death related pathways were then measured. Although EtOH exposure did not further improve cardiac function or reduce reactive oxygen species (ROS) levels in WT mice, levels of high density lipoprotein-cholesterol (HDL-c) and expression of heme oxygenase-1 (HO-1) were significantly elevated in WT-EtOH group. However, EtOH exposure in KO mice depressed cardiac function as indicated by reduced left ventricular ejection fraction (EF) and increased myocardial fibrosis deposition as well as the excessive ROS accumulation. Above changes were related to altered cell demise (apoptosis and necroptosis), as shown by upregulated expression of cleaved caspase 9, cleaved caspase 3 and RIP1/RIP3/MLKL cascade. Our results thus suggest that ALDH2 is indispensable for the favorable cardiac effect of low-to-moderate alcohol consumption and ALDH2 deficiency may lead to unexpected cardiac dysfunctions via enhancing myocardial apoptosis and necroptosis.
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http://dx.doi.org/10.1016/j.bbadis.2016.11.016DOI Listing
August 2017

[Resolvin D1 inhibits the injury of PC12 cells induced by activated microglia].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2016 Nov;32(11):1495-1498

Department of Anesthesiology, First Affiliated Hospital, Zhengzhou University, Henan Key Discipline Laboratory for Clinical Medicine, Zhengzhou 450052, China. *Corresponding author, E-mail:

Objective To investigate the effect of resolvin D1 (RvD1) on the injury of PC12 cells induced by activated BV-2 microglia and the related mechanisms. Methods BV-2 cells were divided into control group, lipopolysaccharide (LPS)-treated group, RvD1-treated group and RvD1 combined with LPS (RvD1-LPS)-treated group. After BV-2 cells were incubated with the corresponding substances for 12 and 24 hours, the levels of interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α) in the supernatants were determined by ELISA. The culture supernatants of BV-2 cells were collected at 24 hours and added into PC12 cells for another 24-hour culture. Thereafter, the survival rate of PC12 cells was tested by MTT assay. The expression of NF-κB p65 protein in BV-2 cells was deteced by Western blotting. Results Compared with the control group, the survival rate of PC12 cells in the LPS group significantly decreased; the levels of IL-1β, IL-6 and TNF-α in the supernatant of BV-2 cells and the nuclear translocation of NF-κB p65 significantly increased in the LPS group. Compared with the LPS group, the survival rate of PC12 cells in RvD1-LPS group was significantly elevated; the levels of IL-1, IL-6, TNF-α and the nuclear translocation of NF-κB p65 were significantly reduced in RvD1-LPS group. Conclusion RvD1 can inhibit the injury of PC12 cells induced by activated BV-2 microglia through inhibiting the nuclear translocation of NF-κB p65 and inflammatory factor levels in BV-2 cells.
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November 2016

Effects of Excess Cr on Trace Element Contents in the Brain and Serum in Chicken.

Biol Trace Elem Res 2017 May 19;177(1):180-186. Epub 2016 Oct 19.

College of Veterinary Medicine, Shandong Agricultural University, Tai'an, 271018, China.

This study aimed to investigate the effects of chromic chloride (CrCl) on Ca, Mg, Mn, Fe, Cu, and Zn contents in the brain and serum of chicken. Seventy-two chickens were randomly divided into four groups and treated with different doses of CrCl via drinking water: 0, 1/8, 1/4, and 1/2 LD for 42 days. The contents of the elements were evaluated through inductively coupled plasma mass spectrometry. Results showed that Cr contents in the brain and serum were higher than those in the control groups, although no significant dose-dependent changes (P > 0.05) in brain of the Cr-treated groups were observed at 42 days. As exposure time was prolonged and CrCl dosage was increased, Ca contents increased (P < 0.05). Mg and Cu contents in serum decreased; by contrast, Mg and Cu contents initially increased and then decreased in the brain. Fe and Zn contents in the serum increased; conversely, Fe and Zn contents in the brain decreased. CrCl exposure did not significantly affect Mn contents at 14 or 28 days, but significantly decreased (P < 0.05) at 42 days. Therefore, excess Cr intake can disrupt absorption and deposition of other trace elements in the brain and serum; the blood-brain barrier may prevent the accumulation of these elements in the brain exposed to CrCl.
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http://dx.doi.org/10.1007/s12011-016-0875-0DOI Listing
May 2017

Mitochondrial aldehyde dehydrogenase 2 deficiency aggravates energy metabolism disturbance and diastolic dysfunction in diabetic mice.

J Mol Med (Berl) 2016 11 3;94(11):1229-1240. Epub 2016 Aug 3.

Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Fenglin Road 180, Shanghai, 200032, People's Republic of China.

Diabetes causes energy metabolism disturbance and may lead to cardiac dysfunction. Mitochondrial aldehyde dehydrogenase 2 (ALDH2) protects cardiac function from myocardial damage. Therefore, understanding of its roles in diabetic heart is critical for developing new therapeutics targeting ALDH2 and mitochondrial function for diabetic hearts. This study investigated the impact of ALDH2 deficiency on diastolic function and energy metabolism in diabetic mice. Diabetes was induced in ALDH2 knockout and wild-type mice by streptozotocin. Cardiac function was determined by echocardiography. Glucose uptake, energy status, and metabolic profiles were used to evaluate cardiac energy metabolism. The association between ALDH2 polymorphism and diabetes was also analyzed in patients. Echocardiography revealed preserved systolic function and impaired diastolic function in diabetic ALDH2-deficient mice. Energy reserves (phosphocreatine/adenosine triphosphate ratio) were reduced in the diabetic mutants and were associated with diastolic dysfunction. Western blot analysis showed that diabetes induces accumulated lipid peroxidation products and escalated AMP-activated protein kinase-LKB1 pathway. Further, ALDH2 deficiency exacerbated the diabetes-induced deficient myocardial glucose uptake and other perturbations of metabolic profiles. Finally, ALDH2 mutations were associated with worse diastolic dysfunction in diabetic patients. Together, our results demonstrate that ALDH2 deficiency and resulting energy metabolism disturbance is a part of pathology of diastolic dysfunction of diabetic hearts, and suggest that patients with ALDH2 mutations are vulnerable to diabetic damage.

Key Message: ALDH2 deficiency exacerbates diastolic dysfunction in early diabetic hearts. ALDH2 deficiency triggers decompensation of metabolic reserves and energy metabolism disturbances in early diabetic hearts. ALDH2 deficiency potentiates oxidative stress and AMPK phosphorylation induced by diabetes via post-translational regulation of LKB1. Diabetic patients with ALDH2 mutations are predisposed to worse diastolic dysfunction.
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http://dx.doi.org/10.1007/s00109-016-1449-5DOI Listing
November 2016

Structure characterization of three polysaccharides and a comparative study of their immunomodulatory activities on chicken macrophage.

Carbohydr Polym 2016 Nov 28;153:631-640. Epub 2016 Jul 28.

College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai'an 271018, PR China. Electronic address:

In this study, we evaluated structure characterization and immunomodulatory activity of polysaccharides from Astragalus aboriginum Richardson (RAPS), Atractylodes macrocephala Koidz (RAMPS) and Rumia seseloides Hoffm (RSPS) in vitro on chicken macrophage. We found that molecular weight of RAPS and RAMPS was 122.4 and 109.4kDa higher than 64.71kDa of RSPS. Glucose occupied 83.95% and 66.39% in RAPS and RAMPS, respectively. RSPS mainly contained glucose and galacturonic acid, which accounted for 32.35% and 29.25%, respectively. The NMR results displayed that RAPS and RAMPS contained β- glucose, β-galactose, and β-galacturonic acid. The backbone was 1→6 linked glucose. RSPS showed at least six monosaccharide response signals. In vitro experiment, the results showed that RAPS at dosage of 15.62μgmL(-1) exhibited significant immunological on chicken macrophage compared to RAMPS and RSPS. Interestingly, costimulatory molecules levels in RSPS group were higher than that of RAPS, which may associated with the special structure of RSPS.
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http://dx.doi.org/10.1016/j.carbpol.2016.07.116DOI Listing
November 2016

Trans-Fatty Acids Aggravate Obesity, Insulin Resistance and Hepatic Steatosis in C57BL/6 Mice, Possibly by Suppressing the IRS1 Dependent Pathway.

Molecules 2016 May 30;21(6). Epub 2016 May 30.

Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032, China.

Trans-fatty acid consumption has been reported as a risk factor for metabolic disorders and targeted organ damages. Nonetheless, little is known about the roles and mechanisms of trans-fatty acids in obesity, insulin resistance (IR) and hepatic steatosis. Adult C57BL/6 male mice were fed with four different diets for 20 weeks: normal diet (ND), high fat diet (HFD), low trans-fatty acids diet (LTD) and high trans-fatty acid diet (HTD). The diet-induced metabolic disorders were assessed by evaluating body weight, glucose tolerance test, hepatic steatosis and plasma lipid profiles post 20-week diet. Histological (H&E, Oil-Red-O) staining and western blot analysis were employed to assess liver steatosis and potential signaling pathways. After 20-weeks of diet, the body weights of the four groups were 29.61 ± 1.89 g (ND), 39.04 ± 4.27 g (HFD), 34.09 ± 2.62 g (LTD) and 43.78 ± 4.27 g (HTD) (p < 0.05), respectively. HFD intake significantly impaired glucose tolerance, which was impaired further in the mice consuming the HTD diet. The effect was further exacerbated by HTD diet. Moreover, the HTD group exhibited significantly more severe liver steatosis compared with HFD group possibly through regulating adipose triglyceride lipase. The group consuming the HTD also exhibited significantly reduced levels of IRS1, phosphor-PKC and phosphor-AKT. These results support our hypothesis that consumption of a diet high in trans-fatty acids induces higher rates of obesity, IR and hepatic steatosis in male C57BL/6 mice, possibly by suppressing the IRS1dependent pathway.
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http://dx.doi.org/10.3390/molecules21060705DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6273562PMC
May 2016

The immune adjuvant response of polysaccharides from Atractylodis macrocephalae Koidz in chickens vaccinated against Newcastle disease (ND).

Carbohydr Polym 2016 May 12;141:190-6. Epub 2016 Jan 12.

College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai'an 271018, PR China. Electronic address:

Build on our previous research, polysaccharides from the rhizome of Atractylodis macrocephalae Koidz (RAMPS), RAMPStp and RAMPS60c were prepared and the structural characterization and immune response of ND vaccine in chicken were investigated. Immune organ index, Lymphocyte proliferation, antibody titers, cell cycle distribution, and percentages of CD4(+) and CD8(+) cells were determined. GPC analysis showed that the Mn of RAMPS with two peaks were 1.29×10(5) and 1.74×10(3), respectively. GC-MS analysis revealed that RAMPS was composed of glucose, mannose, arabinose, galactose, xylose, d-Ribose and rhamnose, with mass percentages of 66.39%, 21.24%, 5.64%, 2.65%, 2.30%, 1.15% and 0.64%, respectively. NMR spectroscopic analysis demonstrated that a preliminary structure of RAMPS was proposed as 1,3-linked β-d-Galp and 1,6-linked β-d-Galpresidues. In vivo test showed that RAMPStp and RAMPS60c could promote peripheral lymphocytes proliferation and entering into S and G2/M phases, enhance serum HI antibody titer and effectively improve the percentages of CD4(+) and CD8(+) T cells in chickens vaccinated with ND vaccine at most time points. The actions of RAMPStp and RAMPS60c were stronger than that of Lev, and RAMPStp presented the best efficacy. These results indicated that RAMPStp and RAMPS60c characterize of the immune-enhancing activity and RAMPStp possessed the strongest activity. It would be anticipated as a component of new-type immunopotentiator.
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http://dx.doi.org/10.1016/j.carbpol.2016.01.013DOI Listing
May 2016

Oxidative Stress and Histological Alterations of Chicken Brain Induced by Oral Administration of Chromium(III).

Biol Trace Elem Res 2016 Sep 12;173(1):185-93. Epub 2016 Feb 12.

College of Veterinary Medicine, Research Center for Animal Disease Control Engineering Shandong Province, Shandong Agricultural University, Tai'an, 271018, China.

This experiment was conducted to investigate the oxidative stress in chickens exposed to different concentrations of chromium trichloride (CrCl3) in drinking water. Seventy-two Hylan Brown male chickens were randomly divided into four groups: three experimental groups and one control group. The experimental groups were exposed to three different doses (50 % LD50, 25 % LD50, and 12.5 % LD50) of CrCl3 mg/kg body weight for 42 days, while the control group was given the equivalent water. The activities of antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) and non-enzymatic index (glutathione, total antioxidant capacity, malondialdehyde, and hydrogen peroxide) were measured after obtaining the brain samples. Results suggested that 50 % LD50 chromium(III) significantly increased (P < 0.05) the contents of malondialdehyde and hydrogen peroxide. The antioxidant enzyme activities, total glutathione concentration, and total antioxidant capacity decreased significantly (P < 0.05) compared with those of the controls and were consistent with the increase in dosage and time. Additionally, extensive histological alterations were observed in the chicken brain, such as the vacuolization and nuclear condensation of the neurons. These results indicated that exposure to high-dose CrCl3 for a certain time could induce the occurrence of oxidative stress and histological alterations.
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http://dx.doi.org/10.1007/s12011-016-0640-4DOI Listing
September 2016

Effects of Oral Administration of CrCl3 on the Contents of Ca, Mg, Mn, Fe, Cu, and Zn in the Liver, Kidney, and Heart of Chicken.

Biol Trace Elem Res 2016 Jun 5;171(2):459-467. Epub 2015 Nov 5.

College of Veterinary Medicine, Shandong Agricultural University, Tai'an, Shandong, 271018, China.

This study aimed to investigate the effects of oral administration of trivalent chromium on the contents of Ca, Mg, Mn, Fe, Cu, and Zn in the heart, liver, and kidney. Different levels of 1/8, 1/4, and 1/2 LD50 (LD50 = 5000 mg/kg body mass) CrCl3 milligrams per kilogram body mass daily were added into the water to establish the chronic poisoning model. Ca, Mg, Mn, Fe, Cu, and Zn were detected with the flame atomic absorption spectrometry in the organs exposed 14, 28, and 42 days to CrCl3, respectively. Results showed that Cr was accumulated in the heart, liver, and kidney significantly (P < 0.05) with extended time and dose. The contents of Ca and Fe increased, whereas those of Mg, Mn, Cu, and Zn decreased in the heart, liver, and kidney of each treated group, which had a dose- and time-dependent relationship, but the contents of Mg and Zn in the heart took on a fluctuated change. These particular observations were different from those in the control group. In conclusion, the oral administration of CrCl3 could change the contents of Ca, Mg, Mn, Fe, Cu, and Zn in the heart, liver, and kidney, which may cause disorders in the absorption and metabolism of the metal elements of chickens.
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http://dx.doi.org/10.1007/s12011-015-0559-1DOI Listing
June 2016
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