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Gastro protective properties of the novel prostone SPI-8811 against acid-injured porcine mucosa

World Journal of Gastroenterology 2012年第34期18卷 4684-4692页

作者： Meghali Nighot Adam Moeser Ryuji Ueno Anthony Blikslager Departments of Clinical Sciences College of Veterinary MedicineNorth Carolina State UniversityRaleighNC 27607United States Departments of Population Health and Patho-biology College of Veterinary MedicineNorth Carolina State UniversityRaleighNC 27607United States Departments of Sucampo Pharmaceuticals Inc.BethesdaMD 20810United States

AIM:To evaluate the protective properties of novel prostone ClC-2 agonist SPI-8811 in porcine model of gastric acid injury. METHODS:Porcine gastric mucosa was mounted in Ussing chambers and injured by bathing mucosal tissues in an HCl Ringer's solution (pH = 1.5) with or without SP1-8811 (1 μmol/L), cystic fibrosis transmem-brane conductance regulator (CFTR) inhibitor (inhibitor 172, 10 μmol/L, apical) and ClC-2 inhibitor ZnCl 2 , 300 μmol/L, apical), on the apical surface of tissues. Transepithelial resistance and mucosal-to-serosal 3 H-mannitol fluxes were measured over a 90-min period. Tissues were analyzed by morph metric techniques, Immunofluorescence and by western blots. RESULTS:Compared with control tissues, acid exposure decreased transepithelial electrical resistance (TER) and increased 3 H-mannitol flux. Pretreatment of gastric mucosa with SPI-8811 was protective against acid-induced decreases in TER (TER, 50 Ω . cm 2 vs 100 Ω . cm 2 ) and abolished increases in flux ( 3 H-mannitol flux, 0.10 μmol/L . cm 2 vs 0.04 μmol/L . cm 2 ). Evidence of histological damage in the presence of acid was markedly at- tenuated by SPI-0811. Immunofluorescence and western analysis for occludin revealed enhanced localization to the region of the tight junction (TJ) after treatment with SPI-8811. Pretreatment with the ClC-2 inhibitor ZnCl 2 , but not the selective CFTR inhibitor 172, attenuated SPI-8811-mediated mucosal protection, suggesting a role for ClC-2. Prostone may serve both protective and reparative roles in injured tissues. CONCLUSION: ClC-2 agonist SPI-8811 stimulated enhancement of mucosal barrier function by protecting TJ protein occludin in porcine gastric mucosa and thus protected the gastric acid injury in porcine stomach.

关键词： Stomach Mucosal permeability CIC-2 chlo-ride channel Tight junction

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McSNAC:A software to approximate first-order signaling networks from mass cytometry data

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Quantitative Biology 2023年第1期11卷 59-71页

作者： Darren Wethington Sayak Mukherjee Jayajit Das Steve and Cindy Rasmussen Institute for Genomic medicine Abigail Wexner Research InstituteNationwide Children’s HospitalColumbusOhio 43205United States Biomedical Sciences Graduate Program College of MedicineThe Ohio State UniversityColumbusOhio 43210United States Department of Pediatrics College of MedicineThe Ohio State UniversityColumbusOhio 43210United States Pelotonia Institute for Immuno-Oncology College of MedicineThe Ohio State UniversityColumbusOhio 43210United States DepartmentofBiomedicalInformatics CollegeofMedicineTheOhioStateUniversityColumbusOhio43210United States Biophysics Graduate Program The Ohio State UniversityColumbusOhio 43210United States Battelle Memorial Institute ColumbusOhio 43201United States

Background:Mass cytometry(CyTOF)gives unprecedented opportunity to simultaneously measure up to 40 proteins in single cells,with a theoretical potential to reach 100 *** high-dimensional single-cell information can be very useful in dissecting mechanisms of cellular *** particular,measuring abundances of signaling proteins like phospho-proteins can provide detailed information on the dynamics of single-cell signaling ***,computational analysis is required to reconstruct such networks with a mechanistic ***:We propose our Mass cytometry Signaling Network Analysis Code(McSNAC),a new software capable of reconstructing signaling networks and estimating their kinetic parameters from CyTOF *** approximates signaling networks as a network of first-order reactions between *** assumption often breaks down as signaling reactions can involve binding and unbinding,enzymatic reactions,and other nonlinear ***,McSNAC may be limited to approximating indirect interactions between protein species,as cytometry experiments are only able to assay a small fraction of protein species involved in ***:We carry out a series of in silico experiments here to show(1)McSNAC is capable of accurately estimating the ground-truth model in a scalable manner when given data originating from a first-order system;(2)McSNAC is capable of qualitatively predicting outcomes to perturbations of species abundances in simple second-order reaction models and in a complex in silico nonlinear signaling network in which some proteins are ***:These findings demonstrate that McSNAC can be a valuable screening tool for generating models of signaling networks from time-stamped CyTOF data.

关键词： single-cell CyTOF data signaling network kinetics ODE McSNAC

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The mechanisms of color production in black skin versus red skin on the heads of New World vultures

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Avian Research 2023年第1期14卷 86-92页

作者： Nicholas M.Justyn Matthew J.Powers Geoffrey E.Hill Kayla Alexander Adrián Naveda-Rodríguez Scott A.Rush Department of Biological Sciences Auburn UniversityAuburnALUSA college of veterinary medicine Mississippi State UniversityMississippiStateMSUSA Department of Wildlife Fisheriesand AquacultureMississippi State UniversityMississippi StateMSUSA

A determination of how the color of animal integument is produced is a starting point for investigations into the function and evolution of *** mechanisms that give rise to the color of bare skin of New World vultures are largely ***,we investigate the source of color production in the bare skin of Turkey Vultures(Cathartes aura)and Black Vultures(Coragyps atratus).Using UV-vis reflectance spectroscopy,we found evidence that hemoglobin is the primary pigment responsible for the red coloration of the bare skin on the heads of Turkey Vultures,and that eumelanin is responsible for the black coloration of the bare skin on the heads of Black *** microscopy of incisional skin samples further supported these mechanisms of color production by revealing the presence of numerous blood vessels near the surface of the Turkey Vulture skin,and a high concentration of melanosomes in the skin of Black *** high performance liquid chromatography(HPLC),we detected carotenoids within the skin of both species with significantly higher total concentrations of carotenoids in the skin of Turkey Vultures compared to the skin of Black *** carotenoids detected were dietary carotenoids that typically produce yellow coloration when accumulated in integument and were present in low *** hypothesize that the dietary carotenoids present do not contribute to the color of the skin,but rather help to compensate for the lack of melanosomes found in Turkey Vulture *** presence of additional carotenoids may act as an antioxidant to minimize UV damage when the bare Turkey Vulture head skin is exposed to direct sunlight for prolonged periods of time when soaring and scavenging for food.

关键词： Carotenoids Cathartes aura Coragyps atratus Hemoglobin High performance liquid chromatography Melanosomes Skin biopsies

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Development of an analytical method for multi-residue quantification of 18 anthelmintics in various animal-based food products using liquid chromatography-tandem mass spectrometry

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Journal of Pharmaceutical Analysis 2021年第1期11卷 68-76页

作者： Kyung-Hee Yoo Da-Hee Park A.M.Abd El-Aty Seong-Kwan Kim Hae-Ni Jung Da-Hye Jeong Hee-Jung Cho Ahmet Hacimuftuoglu Jae-Han Shim Ji Hoon Jeong Ho-Chul Shin Department of veterinary Pharmacology and Toxicology College of Veterinary MedicineKonkuk UniversitySeoul143-701Republic of Korea state Key Laboratory of Biobased Material and Green Papermaking College of Food Science and EngineeringQilu University of TechnologyShandong Academy of ScienceJinan250353China Department of Pharmacology Faculty of Veterinary MedicineCairo University12211GizaEgypt Department of Medical Pharmacology Medical FacultyAtaturk UniversityErzurum25240Turkey Department of veterinary Physiology College of Veterinary MedicineKonkuk UniversitySeoul143-701Republic of Korea Natural Products Chemistry Laboratory College of Agriculture and Life SciencesChonnam National UniversityGwangju500-757Republic of Korea Department of Pharmacology College of MedicineChung-Ang UniversitySeoul156-756Republic of Korea

In this study,we developed a simple screening procedure for the determination of 18 anthelmintics(including benzimidazoles,macrocyclic lactones,salicylanilides,substituted phenols,tetrahydropyrimidines,and imidazothiazoles)in five animal-derived food matrices(chicken muscle,pork,beef,milk,and egg)using liquid chromatography-tandem mass *** were extracted using acetonitrile/1% acetic acid(milk and egg)and acetonitrile/1% acetic acid with 0.5 mL of distilled water(chicken muscle,pork,and beef),and purified using saturated n-hexane/acetonitrile.A reversed-phase analytical column and a mobile phase consisting of(A)10 mM ammonium formate in distilled water and(B)methanol were used to achieve optimal chromatographic ***-matched standard calibration curves(R^(2)≥0.9752)were obtained for concentration equivalent to ×1/2,×1,×2,×3,×4,and×5 fold the maximum residue limit(MRL)stipulated by the Korean Ministry of Food and Drug *** of 61.2e118.4%,with relative standard deviations(RSDs)of ≤19.9%(intraday and interday),were obtained for each sample at three spiking concentrations(×1/2,×1,and ×2 the MRL values).Limits of detection,limits of quantification,and matrix effects were 0.02e5.5 mg/kg,0.06e10 mg/kg,and -98.8 to 13.9%(at 20 μg/kg),*** five samples of each food matrix(chicken muscle,pork,beef,milk,and egg)purchased from large retailers in Seoul that were tested,none of the target analytes were *** has therefore been shown that this protocol is adaptable,accurate,and precise for the quantification of anthelmintic residues in foods of animal origin.

关键词： Anthelmintics Tandem mass spectrometry Animal-based food products Residue analysis Method validation

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Fusobacterium 's link to colorectal neoplasia sequenced: A systematic review and future insights

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World Journal of Gastroenterology 2017年第48期23卷 8626-8650页

作者： Hisham Hussan Steven K Clinton Kristen Roberts Michael T Bailey Division of Gastroenterology Hepatology and NutritionDepartment of Internal MedicineThe Ohio State University Wexner Medical Center Comprehensive Cancer Center The Ohio State University Division of Medical Oncology Department of Internal MedicineThe Ohio State University Wexner Medical Center Department of Pediatrics OSU College of Medicine And Center for Microbial PathogenesisThe Research Institute at Nationwide Children’s Hospital

AIM To critically evaluate previous scientific evidence on Fusobacterium's role in colorectal neoplasia *** Two independent investigators systematically reviewed all original scientific articles published between January,2000,and July,2017,using Pub Med,EMBASE,and MEDLINE. A total of 355 articles were screened at the abstract level. Of these,only original scientific human,animal,and in vitro studies investigating Fusobacterium and its relationship with colorectal cancer(CRC) were included in the analysis. Abstracts,review articles,studies investigating other colonic diseases,and studies written in other languages than English were excluded from our analysis. Ninety articles were included after removing duplicates,resolving disagreements between the two reviewers,and applying the above *** Studies have consistently identified positive associations between Fusobacterium,especially Fusobacterium nucleatum(F. nucleatum),and CRC. Stronger associations were seen in CRCs proximal to the splenic flexure and Cp G island methylator phenotype(CIMP)-high CRCs. There was evidence of temporality and a biological gradient,with increased F. nucleatum DNA detection and quantity along the traditional adenoma-carcinoma sequence and in CIMP-high CRC precursors. Diet may have a differential impact on colonic F. nucleatum enrichment;evidence suggests that high fiber diet may reduce the risk of a subset of CRCs that are F. nucleatum DNA-positive. Data also suggest shorter CRC and disease-specific survival with increased amount of F. nucleatum DNA in CRC tissue. The pathophysiology of enrichment of F. nucleatum and other Fusobacterium species in colonic tissue is unclear;however,the virulence factors and changes to the local colonic environment with disruption of the protective mucus layer may contribute. The presence of a host lectin(Gal-Gal NAc) in the colonic epithelium may also mediate F. nucleatum attachment to CRC and precursors through interaction with a

关键词： Colon microbiota Fusobacterium Systematic review Fusobacterium nucleatum Colorectal cancer Colorectal polyps Carcinogenesis

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The E3 ubiquitin ligase NEDD4-1 protects against acetaminophen-induced liver injury by targeting VDAC1 for degradation

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Acta Pharmaceutica Sinica B 2023年第4期13卷 1616-1630页

作者： Yiwei Zhu Lin Lei Xinghui Wang Linfang Chen Wei Li Jinxia Li Chenchen Zhao Xiliang Du Yuxiang Song Wenwen Gao Guowen Liu Xinwei Li state Key Laboratory for Zoonotic Diseases Key Laboratory of Zoonosis ResearchMinistry of EducationCollege of Veterinary MedicineJilin UniversityChangchun 130062China

Acetaminophen(APAP)overdose is a major cause of liver *** precursor cell expressed developmentally downregulated 4—1(NEDD4-1)is an E3 ubiquitin ligase that has been implicated in the pathogenesis of numerous liver diseases;however,its role in APAP-induced liver injury(AILI)is ***,this study aimed to investigate the role of NEDD4-1 in the pathogenesis of *** found that NEDD4-1 was dramatically downregulated in response to APAP treatment in mouse livers and isolated mouse ***-specific NEDD4-1 knockout exacerbated APAP-induced mitochondrial damage and the resultant hepatocyte necrosis and liver injury,while hepatocyte-specific NEDD4-1 overexpression mitigated these pathological events both in vivo and in ***,hepatocyte NEDD4-1 deficiency led to marked accumulation of voltage-dependent anion channel 1(VDAC1)and increased VDAC1 ***,VDAC1 knockdown alleviated AILI and weakened the exacerbation of AILI caused by hepatocyte NEDD4-1 ***,NEDD4-1 was found to interact with the PPTY motif of VDAC1 through its WW domain and regulate K48-linked ubiquitination and degradation of *** present study indicates that NEDD4-1 is a suppressor of AILI and functions by regulating the degradation of VDAC1.

关键词： Acetaminophen NEDD4-1 VDAC1 Liver injury Hepatotoxicity Necrosis Mitochondrial damage Ubiquitination

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Effect of physiological heterogeneity of E. coli population on antibiotic susceptivity test

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Science China(Life Sciences) 2007年第6期50卷 808-813页

作者： LIU YuQing1,3, ZHANG HuaiQiang2, SHEN JianZhong3 & GAO PeiJi2 1 Institute of Animal Science and veterinary medicine, Shandong Academy of Agricultural Science, Jinan 250100, China 2 state Key Laboratory of Microbial Technology, Shandong university, Jinan 250100, China 3 college of veterinary medicine, China Agricultural university, Beijing 100094, China Institute of Animal Science and veterinary medicine Shandong Academy of Agricultural Science Jinan China college of veterinary medicine China Agricultural University Beijing China state Key Laboratory of Microbial Technology Shandong University Jinan China

According to the instantaneous growth rate (dN/dt) of E. coli CVCC249 growing in batch culture, the entire growth progress was distinguished into four phases: accelerating growth phase, constant growth phase, decelerating growth phase; declining phase, in each of which obvious variation in physiological; biochemical properties was detected, including total DNA, total protein,; MTT-dehydrogenase activity, etc., that led to difference in their antibiotic susceptivity. Antibiotic susceptivity of the population sampled from each phase was tested by Concentration-killing Curve (CKC) approach following the formula N=N 0/{1+exp[r·(x-BC 50)]}, showing as normal distribution at the individual cell level for an internal population, in which the median bactericidal concentration BC 50 represents the mean level of susceptivity, while the bactericidal span BC 199=(2lnN 0)/r indicates the variation degree of the antibiotic susceptivity. Furthermore, tested by CKC approach, the antibiotic susceptivity of E. coli CVCC249 population in each physiological phase to gentamicin or enoxacin was various: susceptivity of the population in the constant growth phase; declining phase all increased compared with that in the accelerating growth phase for gentamicin but declined for enoxacin. The primary investigations revealed that the physiological phase should be taken into account in the context of antibiotic susceptivity; research into antimicrobial mechanism. However there are few reports concerned with this study. Further research using different kinds of antibiotics with synchronized continuous culture of different bacterial strains is required.

关键词： instantaneous growth rate, batch culture, physiological heterogeneity, concentration-killing curve, antibiotic susceptivity test

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Innovations in osteomyelitis research:A review of animal models

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Animal Models and Experimental medicine 2021年第1期4卷 59-70页

作者： Kylie M.Roux Leah H.Cobb Marc A.Seitz Lauren B.Priddy college of veterinary medicine Mississippi State UniversityMississippi StateMSUSA Department of Agricultural and Biological Engineering Mississippi State UniversityMississippi StateMSUSA

Infection of bone tissue,or osteomyelitis,has become a growing concern in modern healthcare due in no small part to a rise in antibiotic resistance among bacteria,notably Staphylococcus *** current standard of care involves aggressive,prolonged antibiotic therapy combined with surgical debridement of infected *** this treatment may be sufficient for resolving a portion of cases,recurrences of the infection and associated risks including toxicity with long-term antibiotic usage have been ***,there exists a need to produce safer,more efficacious options of treatment for *** order to test treatment regimens,animal models that closely mimic the clinical condition and allow for accurate evaluation of therapeutics are *** a model that replicates features of osteomyelitis in humans continues to be a challenge to scientists,as there are many variables involved,including choosing an appropriate species and method to establish *** review addresses the refinement of animal models of osteomyelitis to reflect the clinical disease and test prospective *** aim of this review is to explore studies regarding the use of animals for osteomyelitis therapeutics research and encourage further development of such animal models for the translation of results from the animal experiment to human medicine.

关键词： animal model bone infection orthopedic implant osteomyelitis Staphylococcus aureus

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Effects of magnesium on the performance of sows and their piglets

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Journal of Animal Science and Biotechnology 2015年第1期6卷 55-62页

作者： Jianjun Zang Jingshu Chen Ji Tian Aina Wang Hong Liu Shengdi Hu Xiangrong Che Yongxi Ma Junjun Wang Chunlin Wang Guanghua Du Xi Ma state Key Laboratory of Animal Nutrition Ministry of Agriculture Feed Industry CentreChina Agricultural University Weifang Business Vocational college college of Animal Science and veterinary medicine Shanxi Agricultural University

The objective of this study was to evaluate the effects of supplemental magnesium （Mg） on the performance of gilts and parity 3 sows and their piglets. Fifty-six grits （Trial 1） and 56 sows （Trial 2） were assigned to one of 4 treatments according to their mating weight, respectively. The treatments comprised corn-soybean meal based gestation and lactation diets （0.21% magnesium） supplemented with 0, 0.015, 0.03, or 0.045% Mg from mating until weaning. The results showed that magnesium supplementation significantly （P 〈 0.05） reduced the weaning to estrus interval in both gilts and sows. There were significant effects （P 〈 0.05） of supplemental magnesium on the total number of piglets born, born alive and weaned in sows. In late gestation and lactation, the digestibility of crude fiber （quadratic effects, P 〈 0.05）, and crude protein （P 〈 0.05）, were significantly influenced by magnesium in gilts and sows, respectively. There were differences among the 4 groups in terms of the apparent digestibility of dry matter and crude fiber in sows （P 〈 0.0S） during both early and late gestation. The apparent digestibility of gross energy was increased for sows in late gestation （P 〈 0.05）, and lactation （quadratic effects, P 〈 0.0S）. At farrowing and weaning, serum prolactin levels and alkaline phosphate activities linearly increased in sows as the Mg supplementation increased （P 〈 0.0.5）. Serum Mg of sows at farrowing and serum urea nitrogen of sows at weaning was significantly influenced by Mg supplementation （P 〈 0.05）. The Mg concentration in sow colostrum and the serum of their piglets were increased by supplemental magnesium （P 〈 0.05）. In addition, growth hormone levels were linearly elevated （P 〈 0.05） in the serum of piglets suckling sows. Our data demonstrated that supplemental magnesium has the potential to improve the reproduction performance of sows, and the suitable supplemental dose ranged from 0.015% to 0.03%.

关键词： Gilts Magnesium Piglets Reproduction Sows

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Two Inhibitors Against the 3C-Like Proteases of Swine Coronavirus and Feline Coronavirus

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Virologica Sinica 2021年第6期36卷 1421-1430页

作者： Mengxin Zhou Yutong Han Mengxia Li Gang Ye Guiqing Peng state Key Laboratory of Agricultural Microbiology College of Veterinary MedicineHuazhong Agricultural UniversityWuhan430070China Key Laboratory of Preventive veterinary medicine in Hubei Province The Cooperative Innovation Center for Sustainable Pig ProductionWuhan430070China

Coronaviruses(CoVs)are important human and animal pathogens that cause respiratory and gastrointestinal *** epidemic diarrhoea(PED),characterized by severe diarrhoea and vomiting in pigs,is a highly lethal disease caused by porcine epidemic diarrhoea virus(PEDV)and causes substantial losses in the swine industry ***,currently available commercial drugs have not shown great therapeutic *** this study,a fluorescence resonance energy transfer(FRET)-based assay was applied to screen a library containing 1,590 compounds and identified two compounds,3-(aminocarbonyl)-1-phenylpyridinium and 2,3-dichloronaphthoquinone,that target the 3C-like protease(3CL^(pro))of *** compounds are of low molecular weight(MW)and greatly inhibited the activity of this enzyme(IC_(50) values were obtained in this study).Furthermore,these compounds exhibited antiviral capacity against another member of the CoV family,feline infectious peritonitis virus(FIPV).Here,the inhibitory effects of these compounds against CoVs on Vero cells and feline kidney cells were identified(with EC_(50) values)and cell viability assays were *** results of putative molecular docking models indicate that these compounds,labeled compound 1 and compound 2,contact the conserved active sites(Cys144,Glu165,Gln191)of 3CL^(pro) via hydrogen *** findings provide insight into the antiviral activities of compounds 1 and 2 that may facilitate future research on anti-CoV drugs.

关键词： Coronavirus(CoVs) Inhibitor 3C-like Protease Porcine epidemic diarrhoea virus(PEDV) Feline infectious peritonitis virus(FIPV)

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