Publications by authors named "Chunlan Xu"

23 Publications

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Biogenic selenium nanoparticles by ATCC 393 alleviate the intestinal permeability, mitochondrial dysfunction and mitophagy induced by oxidative stress.

Food Funct 2021 Jun 22. Epub 2021 Jun 22.

The Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi 710072, China.

Selenium (Se) is an essential trace element. Nano-selenium has attracted great attention due to its various biological properties, especially strong antioxidant activity, high bioavailability, and low toxicity. Our previous studies demonstrated that the selenium nanoparticles (SeNPs) synthesized by Lactobacillus casei ATCC 393 (L. casei ATCC 393) alleviate hydrogen peroxide (H2O2)-induced intestinal epithelial barrier dysfunction via the mitochondrial pathway. However, the mechanism of SeNPs exerting antioxidant activity through the mitochondrial pathway remains unclear. This study was conducted to investigate the role of mitophagy in the protective effects of SeNPs on H2O2-induced porcine intestinal epithelial cells against oxidative damage. The results showed that the SeNPs synthesized by L. casei ATCC 393 had no cytotoxicity on IPEC-J2 cells and effectively antagonized the cytotoxicity of 500 μM H2O2 on IPEC-J2 cells. Moreover, SeNPs attenuated the H2O2-induced intestinal epithelial barrier dysfunction and ROS overproduction, as well as alleviated the adenosine triphosphate (ATP) level and the mitochondrial membrane potential (MMP) decrease. In addition, compared to the oxidative stress model group, pretreatment with biogenic SeNPs significantly up-regulated the expression levels of occludin and claudin-1. Moreover, when compared to the oxidative stress model group, SeNPs inhibited the phosphorylation level of the mammalian target of rapamycin (m-TOR), as well as the expression levels of Unc-51-like kinase 1(ULK1), light chain 3 (LC3)-II/LC3-I, PTEN-induced kinase 1 (PINK1) and Parkin proteins. The fluorescence colocalization images of mitochondria and lysosomes demonstrated that SeNPs significantly reduced the fusion of mitochondria and lysosomes when compared to the oxidative stress model group. These results demonstrate that the SeNPs synthesized by L. casei ATCC 393 can effectively alleviate the H2O2-induced intestinal epithelial barrier dysfunction through regulating mTOR/PINK1-mediated mitophagy.
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http://dx.doi.org/10.1039/d0fo03141kDOI Listing
June 2021

Preparation, characterization, and evaluation of anti-inflammatory activities of selenium nanoparticles synthesized by GG799.

Food Funct 2021 Jul;12(14):6403-6415

The Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi 710072, China.

Selenium (Se) is an essential micronutrient that has implications in human diseases, including inflammatory bowel disease (IBD), especially with respect to Se deficiencies. Recently, selenium nanoparticles (SeNPs) have attracted significant attention due to their diversity of biological activities and unique advantages including low toxicity and high biological availability. In this study, an eco-friendly, efficient and low-cost method for synthesis of SeNPs by Kluyveromyces lactis GG799 (K. lactis GG799) was established, and the SeNPs were investigated for their physicochemical properties and anti-inflammatory activities in vivo. K. lactis GG799 was able to successfully transform sodium selenite into bright-red SeNPs with particle sizes of 80 and 150 nm and the nanoparticles accumulated intracellularly. Upon isolation, the SeNPs were found to be mainly capped by proteins and polysaccharides by components analysis. Dietary supplementation with 0.6 mg kg-1 Se (in the form of biogenic SeNPs) effectively attenuated dextran sulphate sodium (DSS)-induced ulcerative colitis (UC) in mice by alleviating oxidative stress and intestinal inflammation. These findings suggested that SeNPs synthesized by K. lactis GG799 may be a promising and safe Se supplement for the prevention and treatment of IBD.
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http://dx.doi.org/10.1039/d1fo01019kDOI Listing
July 2021

Biogenic selenium nanoparticles synthesized by Lactobacillus casei ATCC 393 alleviate diquat-induced intestinal barrier dysfunction in C57BL/6 mice through their antioxidant activity.

Food Funct 2020 Apr;11(4):3020-3031

The Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi 710072, China.

Selenium (Se) as an essential micronutrient plays a crucial role in human health. Biogenic selenium nanoparticles (SeNPs) possess attractive biological properties, biocompatibility, stability and low-toxicity. This study was aimed to investigate the protective effect of biogenic SeNPs of size 50-80 nm synthesized by Lactobacillus casei ATCC 393 (L. casei ATCC 393) on diquat-induced intestinal barrier dysfunction in C57BL/6 mice and the intrinsic mechanisms. Our results showed that oral administration of SeNPs significantly inhibited the increase of the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), diamine oxidase (DAO) and d-lactic acid (d-LA) levels induced by diquat, and increased the total superoxide dismutase (T-SOD), thioredoxin reductase (TrxR) and glutathione peroxidase (GSH-Px) activities in serum and jejunum. Moreover, SeNPs increased the number of goblet cells, decreased the production of reactive oxygen species (ROS), maintained the mitochondrial functions, and improved the expression levels of occludin and claudin-1 in jejunum compared to the diquat-induced oxidative stress model group. In addition, SeNPs activated the nuclear factor (erythroid-derived-2)-like 2 (Nrf2), and improved the protein levels of heme oxygenase (HO)-1 and NADPH dehydrogenase (NQO)-1 compared to other treatment groups. These results suggested that biogenic SeNPs synthesized by L. casei ATCC 393 can protect the intestinal barrier function against oxidative damage via Nrf2-mediated signaling pathway.
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http://dx.doi.org/10.1039/d0fo00132eDOI Listing
April 2020

Lactobacillus casei ATCC 393 alleviates Enterotoxigenic Escherichia coli K88-induced intestinal barrier dysfunction via TLRs/mast cells pathway.

Life Sci 2020 Mar 8;244:117281. Epub 2020 Jan 8.

The Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi 710072, China.

Aims: Mast cells play a crucial role in gastrointestinal physiology and pathophysiology. This study was conducted to investigate the role of mast cells (MCs) in the protective effect of Lactobacillus casei ATCC 393 (L. casei ATCC 393) on intestinal barrier function.

Main Methods: The regulatory effect of L. casei ATCC 393 on intestinal barrier dysfunction and MCs activation induced by Enterotoxigenic Escherichia coli K88 (ETEC K88) were evaluated by porcine mucosal mast cells (PMMCs)-porcine jejunal epithelial cells (IPEC-J2)-L. casei ATCC 393 co-culture experiments in vitro and MCs stabilizer drug experiment in vivo.

Key Findings: Results showed that L. casei ATCC 393 pretreatment effectively alleviated the reduction of cell viability and increase of permeability in ETEC K88-infected IPEC-J2 cells. L. casei ATCC 393 pretreatment inhibited the increase of proinflammatory cytokines and some other MCs mediators, and decrease of anti-inflammatory cytokines in ETEC K88-infected PMMCs. Cromolyn sodium or L. casei ATCC 393 prevented ETEC K88-induced increase of intestinal epithelial cell permeability in IPEC-J2 cells when co-cultivation with PMMCs. Furthermore, cromolyn sodium or L. casei ATCC 393 pretreatment attenuated ETEC K88-induced increase of MCs mediators, mast cell proteases (MCPs) and carboxypeptidase A3 (CPA3) mRNA levels, and down-regulation of tight junction proteins, Toll-like receptor 2 and 4 (TLR2 and TLR4) expression levels in mice challenged by ETEC K88.

Significance: These results indicated that intestinal barrier dysfunction caused by ETEC K88 was mediated by intestinal mast cell activation which can be prevented by L. casei ATCC 393 via TLRs signaling pathway.
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http://dx.doi.org/10.1016/j.lfs.2020.117281DOI Listing
March 2020

Biogenic selenium nanoparticles synthesized by ATCC 393 alleviate intestinal epithelial barrier dysfunction caused by oxidative stress via Nrf2 signaling-mediated mitochondrial pathway.

Int J Nanomedicine 2019 18;14:4491-4502. Epub 2019 Jun 18.

The Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi, People's Republic of China.

Selenium (Se) can exert antioxidative activity and prevent the body from experiencing oxidative injury. Biogenic Se nanoparticles (SeNPs) synthesized by probiotics possess relatively strong chemical stability, high bioavailability, and low toxicity, this makes them potential Se supplements. Previously, we demonstrated that SeNPs synthesized by ATCC 393 can alleviate hydrogen peroxide (HO)-induced human and porcine intestinal epithelial cells' oxidative damage. However, the antioxidant mechanism remains unclear. The possible antioxidant mechanism and protective effect of SeNPs on intestinal epithelial permeability and mitochondrial function were evaluated by establishing an HO-induced oxidative damage model of human colon mucosal epithelial cells (NCM460) and conducting Nrf2 inhibitor interference experiments. Mitochondrial membrane potential (MMP), mitochondrial DNA content, adenosine triphosphate (ATP), ROS, and protein expression levels of Nrf2-related genes were determined. Mitochondrial ultrastructure was visualized by transmission electron microscopy. An amount of 4 μg Se/mL of SeNPs synthesized by ATCC 393 alleviated increase of ROS, reduced ATP and MMP, and maintained intestinal epithelial permeability in NCM460 cells challenged by HO. In addition, SeNPs improved the protein levels of Nrf2, HO-1, and NQO-1. Moreover, SeNPs attenuated the damage of mitochondrial ultrastructure caused by oxidative stress. Nrf2 inhibitor (ML385) abolished the regulatory effect of SeNPs on intracellular ROS production. Data suggest that biogenic SeNPs synthesized by ATCC 393 can protect the intestinal epithelial barrier function against oxidative damage by alleviating ROS-mediated mitochondrial dysfunction via Nrf2 signaling pathway. Biogenic SeNPs are an attractive candidate for potential Se supplement agent in preventing oxidative stress-related intestinal disease by targeting mitochondria.
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http://dx.doi.org/10.2147/IJN.S199193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6593357PMC
October 2019

Biosynthesis of Polysaccharides-Capped Selenium Nanoparticles Using NZ9000 and Their Antioxidant and Anti-inflammatory Activities.

Front Microbiol 2019 26;10:1632. Epub 2019 Jul 26.

The Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, China.

() NZ9000, which has been genetically modified, is the most commonly used host strain for nisin regulated gene expression. Selenium (Se) is an essential trace element in the diet of humans and animals important for the maintenance of health and growth. Biosynthesized Se nanoparticles (SeNPs) that use microorganisms as a vehicle are uniquely advantages in terms of low costs, low toxicity and high bioavailability. This study was aimed at preparing novel functionalized SeNPs by NZ9000 through eco-friendly and economic biotechnology methods. Moreover, its physicochemical characteristics, antioxidant and anti-inflammatory activities were investigated. NZ9000 synthesized elemental red SeNPs when co-cultivated with sodium selenite under anaerobic conditions. Biosynthesized SeNPs by NZ9000 were mainly capped with polysaccharides and significantly alleviated the increase of malondialdehyde (MDA) concentration, the decrease of glutathione peroxidase (GPx) and total superoxide dismutase (T-SOD) activity in porcine intestinal epithelial cells (IPEC-J2) challenged by hydrogen peroxide (HO). SeNPs also prevented the HO-caused reduction of transepithelial electrical resistance (TEER) and the increase of FITC-Dextran fluxes across IPEC-J2. Moreover, SeNPs attenuated the increase of reactive oxygen species (ROS), the reduction of adenosine triphosphate (ATP) and the mitochondrial membrane potential (MMP) and maintained intestinal epithelial permeability in IPEC-J2 cells exposed to HO. In addition, SeNPs pretreatment alleviated the cytotoxicity of Enterotoxigenic (ETEC) K88 on IPEC-J2 cells and maintained the intestinal epithelial barrier integrity by up-regulating the expression of Occludin and Claudin-1 and modulating inflammatory cytokines. Biosynthesized SeNPs by NZ9000 are a promising selenium supplement with antioxidant and anti-inflammatory activities.
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http://dx.doi.org/10.3389/fmicb.2019.01632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6676592PMC
July 2019

Response of intestinal metabolome to polysaccharides from mycelia of Ganoderma lucidum.

Int J Biol Macromol 2019 Feb 2;122:723-731. Epub 2018 Nov 2.

College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an 710119, PR China. Electronic address:

Polysaccharides from the mycelia of Ganoderma lucidum (GLP) can improve intestinal barrier function, regulate intestinal immunity and modulate intestinal microbiota. In the present study, GLP was given via oral administration to rats (100 mg/kg body weight, 21 days) to investigate the metabolomic profiling of caecal contents induced by GLP. Gas chromatography-time of light/mass spectrometry (GC-TOF/MS) was performed to identify the metabolites, followed by biomarker and pathway analysis. The multivariate analysis indicated clear separated clusters between two groups. The significantly different metabolites were characterized, which mainly involved in vitamin B6 metabolism, pyrimidine metabolism, fructose and mannose metabolism, and alanine, aspartate and glutamate metabolism. Indolelactate and 2,2‑dimethylsuccinic acid were selected as key biomarkers responded to GLP administration. Furthermore, significantly different metabolites identified were associated with the improvement of intestinal immunological function and regulation of intestinal microbiota. Our results provided a potential metabolomic mechanism of health-beneficial properties of polysaccharides from the mycelia of G. lucidum, which might be used as functional agents to regulate the intestinal functions.
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http://dx.doi.org/10.1016/j.ijbiomac.2018.10.224DOI Listing
February 2019

Biogenic Synthesis of Novel Functionalized Selenium Nanoparticles by ATCC 393 and Its Protective Effects on Intestinal Barrier Dysfunction Caused by Enterotoxigenic K88.

Front Microbiol 2018 18;9:1129. Epub 2018 Jun 18.

The Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, China.

Selenium (Se) is an essential element for human and animal health. Biogenic selenium nanoparticles (SeNPs) by microorganism possess unique physical and chemical properties and biological activities compared with inorganic Se and organic Se. The study was conducted to investigate the mainly biological activities of SeNPs by ATCC 393 ( 393). The results showed that 393 transformed sodium selenite to red SeNPs with the size of 50-80 nm, and accumulated them intracellularly. 393-SeNPs promoted the growth and proliferation of porcine intestinal epithelial cells (IPEC-J2), human colonic epithelial cells (NCM460), and human acute monocytic leukemia cell (THP-1)-derived macrophagocyte. 393-SeNPs significantly inhibited the growth of human liver tumor cell line-HepG2, and alleviated diquat-induced IPEC-J2 oxidative damage. Moreover, and experimental results showed that administration with 393-SeNPs protected against Enterotoxigenic K88 (ETEC K88)-caused intestinal barrier dysfunction. ETEC K88 infection-associated oxidative stress (glutathione peroxidase activity, total superoxide dismutase activity, total antioxidant capacity, and malondialdehyde) was ameliorated in 393-SeNPs-treated mice. These findings suggest that 393-SeNPs with no cytotoxicity play a key role in maintaining intestinal epithelial integrity and intestinal microflora balance in response to oxidative stress and infection.
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http://dx.doi.org/10.3389/fmicb.2018.01129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6015882PMC
June 2018

Responses of Intestinal Mucosal Barrier Functions of Rats to Simulated Weightlessness.

Front Physiol 2018 14;9:729. Epub 2018 Jun 14.

Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, China.

Exposure to microgravity or weightlessness leads to various adaptive and pathophysiological alterations in digestive structures and physiology. The current study was carried out to investigate responses of intestinal mucosal barrier functions to simulated weightlessness, by using the hindlimb unloading rats model. Compared with normal controls, simulated weightlessness damaged the intestinal villi and structural integrity of tight junctions, up-regulated the expression of pro-apoptotic protein Bax while down-regulated the expression of anti-apoptotic protein Bcl-2, thus improved the intestinal permeability. It could also influence intestinal microbiota composition with the expansion of Bacteroidetes and decrease of Firmicutes. The predicted metagenomic analysis emphasized significant dysbiosis associated differences in genes involved in membrane transport, cofactors and vitamins metabolism, energy metabolism, and genetic information processing. Moreover, simulated weightlessness could modify the intestinal immune status characterized by the increase of proinflammatory cytokines, decrease of secretory immunoglobulin A, and activation of TLR4/MyD88/NF-κB signaling pathway in ileum. These results indicate the simulated weightlessness disrupts intestinal mucosal barrier functions in animal model. The data also emphasize the necessity of monitoring and regulating astronauts' intestinal health during real space flights to prevent breakdowns in intestinal homeostasis of crewmembers.
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http://dx.doi.org/10.3389/fphys.2018.00729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6011188PMC
June 2018

Preparation, characteristics and antioxidant activity of polysaccharides and proteins-capped selenium nanoparticles synthesized by Lactobacillus casei ATCC 393.

Carbohydr Polym 2018 Sep 30;195:576-585. Epub 2018 Apr 30.

The Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi, 710072, China.

Selenium (Se) is an essential element nutrient for human and animal health. Biogenic selenium nanoparticles (SeNPs) by microorganism possesses unique physical and chemical properties and biological activities compared to inorganic selenium and organic selenium. The study was conducted to establish a green, efficient and low-cost biotechnology for biogenic synthesis of SeNPs by Lactobacillus casei ATCC 393 (L. casei 393), and investigate its characteristics and antioxidant activities in vitro. The results showed that L. casei 393 transforms sodium selenite to SeNPs under anaerobic conditions. Moreover, 50-80 nm SeNPs were accumulated in the intracellular L. casei 393. The whole bacteria present distinct bright red color. SeNPs were isolated and characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), energy dispersive X-ray spectrometry (EDX), X-ray photoelectron spectroscopy (XPS), and fourier transform infrared spectroscopy (FT-IR). The results showed that the extracted SeNPs were capped by proteins and polysaccharides. Extracted biogenic SeNPs by L. casei 393 at a concentration less than 25 μg Se/mL had no cytotoxicity on the growth and proliferation of human normal epithelial cell (NCM460). The toxicity order of different selenium forms was: Sodium selenite > Selenium methionine > SeNPs synthesized by L. casei 393. Moreover, biogenic SeNPs by L. casei 393 induced HepG2 cells apoptosis via caspase cascade signaling and endocytosis of SeNPs. Moreover, SeNPs alleviated diquat or hydrogen peroxide (HO)-caused oxidative damage in intestinal epithelial cells, and reduced malondialdehyde (MDA) concentration and increased glutathione peroxidase (GPx) activity in culture medium. The findings suggest that biomolecules capped-SeNPs synthesized by probiotic L. casei 393 possess significant antioxidant and anticancer activities, and probiotic bacteria can provide a better alternative to synthesize biogenic elemental selenium particles with potential applications as anticancer and antioxidant agents.
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http://dx.doi.org/10.1016/j.carbpol.2018.04.110DOI Listing
September 2018

Ceragenin CSA13 Reduces Clostridium difficile Infection in Mice by Modulating the Intestinal Microbiome and Metabolites.

Gastroenterology 2018 05 31;154(6):1737-1750. Epub 2018 Jan 31.

Center for Inflammatory Bowel Diseases, Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, California. Electronic address:

Background & Aims: Clostridium difficile induces intestinal inflammation by releasing toxins A and B. The antimicrobial compound cationic steroid antimicrobial 13 (CSA13) has been developed for treating gastrointestinal infections. The CSA13-Eudragit formulation can be given orally and releases CSA13 in the terminal ileum and colon. We investigated whether this form of CSA13 reduces C difficile infection (CDI) in mice.

Methods: C57BL/6J mice were infected with C difficile on day 0, followed by subcutaneous administration of pure CSA13 or oral administration of CSA13-Eudragit (10 mg/kg/d for 10 days). Some mice were given intraperitoneal vancomycin (50 mg/kg daily) on days 0-4 and relapse was measured after antibiotic withdrawal. The mice were monitored until day 20; colon and fecal samples were collected on day 3 for analysis. Blood samples were collected for flow cytometry analyses. Fecal pellets were collected each day from mice injected with CSA13 and analyzed by high-performance liquid chromatography or 16S sequencing; feces were also homogenized in phosphate-buffered saline and fed to mice with CDI via gavage.

Results: CDI of mice caused 60% mortality, significant bodyweight loss, and colonic damage 3 days after infection; these events were prevented by subcutaneous injection of CSA13 or oral administration CSA13-Eudragit. There was reduced relapse of CDI after administration of CSA13 was stopped. Levels of CSA13 in feces from mice given CSA13-Eudragit were significantly higher than those of mice given subcutaneous CSA13. Subcutaneous and oral CSA13 each significantly increased the abundance of Peptostreptococcaceae bacteria and reduced the abundance of C difficile in fecal samples of mice. When feces from mice with CDI and given CSA13 were fed to mice with CDI that had not received CSA13, the recipient mice had significantly increased rates of survival. CSA13 reduced fecal levels of inflammatory metabolites (endocannabinoids) and increased fecal levels of 4 protective metabolites (ie, citrulline, 3-aminoisobutyric acid, retinol, and ursodeoxycholic acid) in mice with CDI. Oral administration of these CSA13-dependent protective metabolites reduced the severity of CDI.

Conclusions: In studies of mice, we found the CSA13-Eudragit formulation to be effective in eradicating CDI by modulating the intestinal microbiota and metabolites.
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http://dx.doi.org/10.1053/j.gastro.2018.01.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5927842PMC
May 2018

CSA13 inhibits colitis-associated intestinal fibrosis via a formyl peptide receptor like-1 mediated HMG-CoA reductase pathway.

Sci Rep 2017 11 27;7(1):16351. Epub 2017 Nov 27.

Center for Inflammatory Bowel Diseases, Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, 90095, USA.

Many Crohn's disease (CD) patients develop intestinal strictures, which are difficult to prevent and treat. Cationic steroid antimicrobial 13 (CSA13) shares cationic nature and antimicrobial function with antimicrobial peptide cathelicidin. As many functions of cathelicidin are mediated through formyl peptide receptor-like 1 (FPRL1), we hypothesize that CSA13 mediates anti-fibrogenic effects via FPRL1. Human intestinal biopsies were used in clinical data analysis. Chronic trinitrobenzene sulfonic acid (TNBS) colitis-associated intestinal fibrosis mouse model with the administration of CSA13 was used. Colonic FPRL1 mRNA expression was positively correlated with the histology scores of inflammatory bowel disease patients. In CD patients, colonic FPRL1 mRNA was positively correlated with intestinal stricture. CSA13 administration ameliorated intestinal fibrosis without influencing intestinal microbiota. Inhibition of FPRL1, but not suppression of intestinal microbiota, reversed these protective effects of CSA13. Metabolomic analysis indicated increased fecal mevalonate levels in the TNBS-treated mice, which were reduced by the CSA13 administration. CSA13 inhibited colonic HMG-CoA reductase activity in an FPRL1-dependent manner. Mevalonate reversed the anti-fibrogenic effect of CSA13. The increased colonic FPRL1 expression is associated with severe mucosal disease activity and intestinal stricture. CSA13 inhibits intestinal fibrosis via FPRL1-dependent modulation of HMG-CoA reductase pathway.
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http://dx.doi.org/10.1038/s41598-017-16753-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5703874PMC
November 2017

Design, Recombinant Fusion Expression and Biological Evaluation of Vasoactive Intestinal Peptide Analogue as Novel Antimicrobial Agent.

Molecules 2017 Nov 14;22(11). Epub 2017 Nov 14.

The Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an 710072, China.

Antimicrobial peptides represent an emerging category of therapeutic agents with remarkable structural and functional diversity. Modified vasoactive intestinal peptide (VIP) (VIP analogue 8 with amino acid sequence "FTANYTRLRRQLAVRRYLAAILGRR") without haemolytic activity and cytotoxicity displayed enhanced antimicrobial activities against () ATCC 25923 and () ATCC 25922 than parent VIP even in the presence of 180 mM NaCl or 50 mM MgCl₂, or in the range of pH 4-10. VIP analogue 8 was expressed as fusion protein thioredoxin (Trx)-VIP8 in BL21(DE) at a yield of 45.67 mg/L. The minimum inhibitory concentration (MIC) of the recombinant VIP analogue 8 against ATCC 25923 and ATCC 25922 were 2 μM. These findings suggest that VIP analogue 8 is a promising candidate for application as a new and safe antimicrobial agent.
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http://dx.doi.org/10.3390/molecules22111963DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6150413PMC
November 2017

Discovery of selective cystathionine β-synthase inhibitors by high-throughput screening with a fluorescent thiol probe.

Medchemcomm 2017 Jan 15;8(1):198-201. Epub 2016 Nov 15.

Key Laboratory for Space Bioscience and Space Biotechnology , School of Life Sciences , Northwestern Polytechnical University , Xi'an , 710072 , China . Email:

A high-throughput assay was developed to identify inhibitors of cystathionine β-synthase (CBS), which is one of three key enzymes involved in HS biosynthesis. Screening of 6491 natural compounds identified several selective CBS inhibitors, which suppressed the proliferation of HT29 cancer cells, with IC values of less than 10 μM.
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http://dx.doi.org/10.1039/c6md00493hDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6072345PMC
January 2017

Effects of polysaccharide from mycelia of Ganoderma lucidum on intestinal barrier functions of rats.

Int J Biol Macromol 2017 Jan 29;94(Pt A):1-9. Epub 2016 Sep 29.

Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, 710072, PR China.

The intestinal mucosal barriers play essential roles not only in the digestion and absorption of nutrients, but also the innate defense against most intestinal pathogens. In the present study, polysaccharide from the mycelia of Ganoderma lucidum was given via oral administration to rats (100mg/kg body weight, 21days) to investigate its effects on intestinal barrier functions, including the mechanical barrier, immunological barrier and biological barrier function. It was found that the polysaccharide administration could significantly up-regulate the expression of occludin, nuclear factor-κB p65 (NF-κB p65) and secretory immunoglobulin A (SIgA) in ileum, markedly improve the levels of interferon-γ (IFN-γ), interleukin-2 (IL-2), and IL-4, and decrease the level of diamine oxidase (DAO) in serum. Meanwhile, rats from the polysaccharide group showed significant higher microbiota richness in cecum as reflected by the Chao 1 index compared with the control group. Moreover, the polysaccharide decreased the Firmicutes-to-Bacteroidetes ratio. Our results indicated that the polysaccharide from the mycelia of G. lucidum might be used as functional agent to regulate the intestinal barrier functions.
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http://dx.doi.org/10.1016/j.ijbiomac.2016.09.099DOI Listing
January 2017

Immunomodulatory and Antioxidant Effects of Polysaccharides from Gynostemma pentaphyllum Makino in Immunosuppressed Mice.

Molecules 2016 Aug 19;21(8). Epub 2016 Aug 19.

The Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an 710072, Shaanxi, China.

The immunomodulatory and antioxidant activities of crude polysaccharides extracted from Gynostemma pentaphyllum Makino (GPMPP) were investigated. GPMPP was composed of rhamnose, arabinose, xylose, mannose, glucose and galactose in the molar ratio of 1.39:3.76:1.00:1.64:4.98:5.88. In vivo studies showed GPMPP significantly increased the spleen and thymus indices, activated the macrophage phagocytosis and NK cells, and exhibited activity on none or Con A/LPS-stimulated splenocytes in a dose-dependent manner in C57BL/6 mice. Moreover, GPMPP elevated CD4⁺ T lymphocyte counts as well as the CD4⁺/CD8⁺ ratio dose-dependently, and it increased IL-2 level in the sera and spleen of Cy-immunosuppressed mice. Furthermore, GPMPP significantly increased the SOD, GSH-Px, T-AOC, GSH and CAT level, and decreased the MDA level. The results showed that GPMPP might play an important role in prevention of oxidative damage in immunological system. These findings indicate GPMPP has immunomodulatory activity in vivo and seems to be an effective natural immunomodulatory agent.
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http://dx.doi.org/10.3390/molecules21081085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6273250PMC
August 2016

Probiotic Saccharomyces boulardii CNCM I-745 prevents outbreak-associated Clostridium difficile-associated cecal inflammation in hamsters.

Am J Physiol Gastrointest Liver Physiol 2016 10 11;311(4):G610-G623. Epub 2016 Aug 11.

Inflammatory Bowel Disease Research Center, Division of Digestive Diseases, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California;

C. difficile infection (CDI) is a common debilitating nosocomial infection associated with high mortality. Several CDI outbreaks have been attributed to ribotypes 027, 017, and 078. Clinical and experimental evidence indicates that the nonpathogenic yeast Saccharomyces boulardii CNCM I-745 (S.b) is effective for the prevention of CDI. However, there is no current evidence suggesting this probiotic can protect from CDI caused by outbreak-associated strains. We used established hamster models infected with outbreak-associated C. difficile strains to determine whether oral administration of live or heat-inactivated S.b can prevent cecal tissue damage and inflammation. Hamsters infected with C. difficile strain VPI10463 (ribotype 087) and outbreak-associated strains ribotype 017, 027, and 078 developed severe cecal inflammation with mucosal damage, neutrophil infiltration, edema, increased NF-κB phosphorylation, and increased proinflammatory cytokine TNFα protein expression. Oral gavage of live, but not heated, S.b starting 5 days before C. difficile infection significantly reduced cecal tissue damage, NF-κB phosphorylation, and TNFα protein expression caused by infection with all strains. Moreover, S.b-conditioned medium reduced cell rounding caused by filtered supernatants from all C. difficile strains. S.b-conditioned medium also inhibited toxin A- and B-mediated actin cytoskeleton disruption. S.b is effective in preventing C. difficile infection by outbreak-associated via inhibition of the cytotoxic effects of C. difficile toxins.
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http://dx.doi.org/10.1152/ajpgi.00150.2016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5142203PMC
October 2016

Effect of iron supplementation on the expression of hypoxia-inducible factor and antioxidant status in rats exposed to high-altitude hypoxia environment.

Biol Trace Elem Res 2014 Dec 8;162(1-3):142-52. Epub 2014 Nov 8.

The Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, 127 West Youyixi Road, Xi'an, Shaanxi, 710072, People's Republic of China,

Iron and oxygen are essential substance for cellular activity in body tissues. Hypoxia-inducible factors (HIFs) can respond to available oxygen changes in the cellular environment and regulate the transcription of a series of target genes. The study was conducted to investigate the effects of iron supplementation on the expression of hypoxia-inducible factor-1 alpha (HIF-1α) and antioxidant status in rats exposed to high-altitude hypoxia environment. Forty rats were divided into control (CON), hypobaric hypoxia (HH), and hypobaric hypoxia plus ferrous sulfate (FeSO4) (9.93 mg/kg body weight (BW)/day) (HFS) and hypobaric hypoxia plus iron glycinate chelate (Fe-Gly) (11.76 mg/kg BW/day) (HFG) groups. Results showed that Fe-Gly effectively alleviated weight loss and intestinal mucosa damage induced by hypobaric hypoxia, whereas FeSO4 aggravated hypobaric hypoxia-induced weight loss, liver enlargement, spleen atrophy, and intestinal damage. Iron supplementation decreased liver superoxide dismutase (T-SOD) and catalase (CAT) activity (P < 0.01) and increased iron concentration in the liver compared to HH group (P < 0.001). Moreover, Fe-Gly upregulated liver transferrin expression in messenger RNA (mRNA) level (P < 0.05) and downregulated serum erythropoietin (EPO) concentration (P < 0.01) and liver HIF-1α expression level (P < 0.05 in mRNA level; P < 0.001 in protein level) compared to HH group. The study indicated that FeSO4 supplementation at high altitudes aggravated the oxidative damage of tissues and organs that could be mediated through production of malondialdehyde (MDA) and inhibition antioxidant enzyme activities. Fe-Gly can protect hypobaric hypoxia-induced tissues injury. Moreover, iron supplementation at high altitudes affected HIF-1α-mediated regulating expression of targeting genes such as EPO and transferrin. The study highlights that iron supplementation under hypobaric hypoxia environment has possible limitation, and efficient supplementation form and dosage need careful consideration.
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http://dx.doi.org/10.1007/s12011-014-0166-6DOI Listing
December 2014

Effect of vitamin e supplementation on intestinal barrier function in rats exposed to high altitude hypoxia environment.

Korean J Physiol Pharmacol 2014 Aug 13;18(4):313-20. Epub 2014 Aug 13.

Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi 710072, P.R.China.

The study was conducted to investigate the role of vitamin E in the high altitude hypoxia-induced damage to the intestinal barrier in rats. Sprague-Dawley rats were divided into control (Control), high altitude hypoxia (HH), and high altitude hypoxia+vitamin E (250 mg/kg BW*d) (HV) groups. After the third day, the HH and HV groups were placed in a hypobaric chamber at a stimulated elevation of 7000 m for 5 days. The rats in the HV group were given vitamin E by gavage daily for 8 days. The other rats were given equal volume saline. The results showed that high altitude hypoxia caused the enlargement of heart, liver, lung and kidney, and intestinal villi damage. Supplementation with vitamin E significantly alleviated hypoxia-caused damage to the main organs including intestine, increased the serum superoxide dismutase (SOD) (p< 0.05), diamino oxidase (DAO) (p< 0.01) levels, and decreased the serum levels of interleukin-2 (IL-2) (p< 0.01), interleukin-4 (IL-4) (p<0.001), interferon-gamma (IFN-γ) (p<0.01) and malondialdehyde (MDA) (p<0.001), and decreased the serum erythropoietin (EPO) activity (p<0.05). Administration of vitamin E significantly increased the S-IgA (p<0.001) in ileum and significantly improved the expression levels of occludin and IκBα, and decreased the expression levels of hypoxia-inducible factor 1 alpha and 2 alpha (HIF-1α and HIF-2α), Toll-like receptors (TLR4), P-IκBα and nuclear factor-κB p65(NF-κB P65) in ileum compared to the HH group. This study suggested that vitamin E protectis from intestinal injury caused by high altitude hypoxia environment. These effects may be related to the HIF and TLR4/NF-κB signaling pathway.
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http://dx.doi.org/10.4196/kjpp.2014.18.4.313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4146633PMC
August 2014

Modulatory effects of vasoactive intestinal peptide on intestinal mucosal immunity and microbial community of weaned piglets challenged by an enterotoxigenic Escherichia coli (K88).

PLoS One 2014 7;9(8):e104183. Epub 2014 Aug 7.

The Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi, China.

Toll-like receptors (TLRs) recognize microbial pathogens and trigger immune response, but their regulation by neuropeptide-vasoactive intestinal peptide (VIP) in weaned piglets infected by enterotoxigenic Escherichia coli (ETEC) K88 remains unexplored. Therefore, the study was conducted to investigate its role using a model of early weaned piglets infected by ETEC K88. Male Duroc × Landrace × Yorkshire piglets (n = 24) were randomly divided into control, ETEC K88, VIP, and ETEC K88+VIP groups. On the first three days, ETEC K88 and ETEC K88+VIP groups were orally administrated with ETEC K88, other two groups were given sterile medium. Then each piglet from VIP and ETEC K88+VIP group received 10 nmol VIP intraperitoneally (i.p.) once daily, on day four and six. On the seventh day, the piglets were sacrificed. The results indicated that administration of VIP improved the growth performance, reduced diarrhea incidence of ETEC K88 challenged pigs, and mitigated the histopathological changes of intestine. Serum levels of IL-2, IL-6, IL-12p40, IFN-γ and TNF-α in the ETEC K88+ VIP group were significantly reduced compared with those in the ETEC group. VIP significantly increased IL-4, IL-10, TGF-β and S-IgA production compared with the ETEC K88 group. Besides, VIP could inhibit the expression of TLR2, TLR4, MyD88, NF-κB p65 and the phosphorylation of IκB-α, p-ERK, p-JNK, and p-38 induced by ETEC K88. Moreover, VIP could upregulate the expression of occludin in the ileum mucosa compared with the ETEC K88 group. Colon and caecum content bacterial richness and diversity were lower for pigs in the ETEC group than the unchallenged groups. These results demonstrate that VIP is beneficial for the maturation of the intestinal mucosal immune system and elicited local immunomodulatory activities. The TLR2/4-MyD88 mediated NF-κB and MAPK signaling pathway may be critical to the mechanism underlying the modulatory effect of VIP on intestinal mucosal immune function and bacterial community.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0104183PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4125177PMC
April 2015

Synthesis, biocompatible, and self-assembly properties of poly (ethylene glycol)/lactobionic acid-grafted chitosan.

J Biomater Sci Polym Ed 2014 Jul 21;25(10):1062-75. Epub 2014 May 21.

Polymers with targeted ligands are widely used as the anti-cancer drug delivery materials. For applications of chitosan as an anti-liver cancer drug delivery, poly (ethylene glycol)/lactobionic acid-grafted chitosan (PEG/LA-CS) was prepared and investigated since lactobionic acid can be specifically recognized by the hepatocytes. The structure of the PEG/LA-CS was characterized by Fourier transform infrared spectrometry and elemental analysis. The self-assembly behaviors of the PEG/LA-CS were monitored by steady-state fluorescence spectroscopy and electronic transmission microscope. The protein adsorption of the PEG/LA-CS was detected with bovine serum albumin (BSA) by electrochemical impedance spectroscopy. The results showed that the PEG/LA-CS almost did not adsorb protein. To study the effects of PEG/LA-CS on the structure of BSA, the interactions between the PEG/LA-CS and BSA were detected by ultraviolet spectrum, fluorescence spectrum, and circular dichroism. All the data gave one result that BSA maintained its original folded confirmation in PEG/LA-CS solution. The hemocompatibility of PEG/LA-CS was investigated by observing the effects of PEG/LA-CS on the hemolysis rate and the plasma recalcification time (PRT). The results showed that the PRT was prolonged greatly and the hemolysis rate was less than 5%. Furthermore, PEG/LA-CS also showed good cytocompatibility with K562, Hep G2, and LO2 cells. Therefore, the PEG/LA-CS is believed to have great potential for producing injectable anti-liver cancer drug delivery.
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http://dx.doi.org/10.1080/09205063.2014.918465DOI Listing
July 2014

Isolation, structure and bioactivities of the polysaccharides from Angelica sinensis (Oliv.) Diels: a review.

Carbohydr Polym 2012 Jul 28;89(3):713-22. Epub 2012 Apr 28.

Key Laboratory for Space Bioscience and Biotechnology, Institute of Special Environmental Biophysics, School of Life Sciences, Northwestern Polytechnical University, 127 Youyi Xilu, Xi'an 710072, PR China.

The root of Angelica sinensis (Oliv.) Diels, a well-known Chinese herbal medicine, has been used historically as a tonic, hematopoietic and anti-inflammatory agent for thousands of years. Modern phytochemistry and pharmacological experiments have proved that polysaccharide is one of the major active ingredients in A. sinensis. It has been demonstrated that A. sinensis polysaccharides had various important biological activities, such as hematopoiesis, immunomodulation, antitumor, antioxidant, radioprotection and hypoglycemic activity. The purpose of the present review is to summarize previous and current references regarding extraction and purification techniques as well as structural characterization and biological activities of A. sinensis polysaccharides.
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http://dx.doi.org/10.1016/j.carbpol.2012.04.049DOI Listing
July 2012

Solid-phase synthesis and antibiotic activities of cyclodecapeptides on the scaffold of naturally occurring Laterocidin.

Bioorg Med Chem Lett 2010 Jan 10;20(1):164-7. Epub 2009 Nov 10.

Faculty of Life Science, Northwestern Polytechnical University, Xi'an 710072, PR China.

The development of new antibacterial therapeutic agents capable of halting microbial resistance is a chief pursuit in clinical medicine. Laterocidin and its analogues were synthesized for the first time by solid-phase synthesis method via linking of the carboxyl group on side chain of Aspartate to Rink resin with the protection of side chain alpha-carboxyl group of Aspartate by Dmab as a temporary alpha-COOH protecting group for the on-resin cyclization. Different configuration of N- and C-terminal was benefit to peptide cyclization. Laterocidin analogue 3 (Asp(1)-->Asn(1), Phe(4)-->Tyr(4) and d-Tyr(6)-->d-Phe(6)) demonstrated potent and broad antimicrobial properties, especially exhibited activity against clinical Methicillin-resistant Staphylococcus aureus (L-MRSA) and the gram-negative extended-spectrum beta-lactamases-producing Escherichia coli (ESBLs E. coli) and L-E.coli. This finding has important significance to exploit new antibiotic medicine.
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http://dx.doi.org/10.1016/j.bmcl.2009.11.009DOI Listing
January 2010
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