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Diabetes exacerbates inflammatory bowel disease in mice with dietinduced obesity

世界胃肠病学杂志:英文版 2023年第33期29卷 4991-5004页

作者： Kendra L Francis Kimberly m Alonge maria Cristina Pacheco Shannon J Hu Cody A Krutzsch gregory J morton michael W Schwartz Jarrad m Scarlett Department of Pediatric Gastroenterology and Hepatology Seattle Children’s HospitalSeattleWA 98105United States 不详 Department of medicinal Chemistry University of WashingtonSeattleWA 98195United States Department of Laboratory medicine and Pathology Seattle Children's HospitalSeattleWA 98105United States

BACKGROUND The increased prevalence of inflammatory bowel disease(IBD)among patients with obesity and type 2 diabetes suggests a causal link between these diseases,potentially involving the effect of hyperglycemia to disrupt intestinal barrier *** To investigate whether the deleterious impact of diabetes on the intestinal barrier is associated with increased IBD severity in a murine model of colitis in mice with and without diet-induced *** mice were fed chow or a high-fat diet and subsequently received streptozotocin to induce diabetic-range *** weeks later,dextran sodium sulfate was given to induce *** select experiments,a subset of diabetic mice was treated with the antidiabetic drug dapagliflozin prior to colitis *** included both clinical and histological measures of colitis activity as well as histochemical markers of colonic epithelial barrier *** In mice given a high-fat diet,but not chow-fed animals,diabetes was associated with significantly increased clinical colitis activity and histopathologic markers of disease *** was also associated with a decrease in key components that regulate colonic epithelial barrier integrity(colonic mucin layer content and epithelial tight junction proteins)in diet-induced obese *** of these effects of diabetes in diet-induced obese mice was ameliorated by restoring *** In obese mice,diabetes worsened clinical and pathologic outcomes of colitis via mechanisms that are reversible with treatment of ***-induced intestinal barrier dysfunction offers a plausible mechanism linking diabetes to increased colitis *** findings suggest that effective diabetes management may decrease the clinical severity of IBD.

关键词： Inflammatory bowel disease Type 2 diabetes Obesity Intestinal barrier Hyperglycemia Colitis in mice Tight junction proteins

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Stability study on an anti-cancer drug 4-(3,5-bis(2-chlorobenzylidene)-4-oxo-piperidine-1-yl)-4-oxo-2-butenoic acid (CLEFmA) using a stabilityindicating HPLC method

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Journal of Pharmaceutical Analysis 2017年第1期7卷 1-9页

作者： Dhawal Raghuvanshi gregory Nkepang Alamdar Hussain Hooman Yari Vibhudutta Awasthi Department of Pharmaceutical Sciences University of Oklahoma Health Science Center 1110 N. Stonewall Avenue Oklahoma City OK 73117 USA

CLEFmA, 4-(3,5-bis(2-chlorobenzylidene)-4-oxo-piperidine-1-yl)-4-oxo-2-butenoic acid, is a new chemical entity with anti-cancer and anti-inflammatory activities. Here, we report its stability in solution against stress conditions of exposure to acid/base, light, oxidant, high temperature, and plasma. The identity of the degradation products was ascertained by mass and proton nuclear magnetic resonance spectroscopy. To facilitate this study, we developed and validated a reverse phase high performance liquid chromatography method for detection of CLEFmA and its degradation. The method was linear over a range of 1–100 μg/m L; the accuracy and precision were within acceptable limits; it was stability-indicating as it successfully separated cis-/trans-isomers of CLEFmA as well as its degradation product. The major degradation product was produced from amide hydrolysis at maleic acid functionality caused by an acidic buffer, oxidant(3% hydrogen peroxide),or temperature stress(40–60 °C). The log k-p H profile showed that CLEFmA was most stable at neutral p H. In accelerated stability study we found that the shelf-life(T_(90%)) of CLEFmA at 25 °C and 4 °C was 45 days and220 days, respectively. Upon exposure to UV-light(365 nm), the normally prevalent trans-CLEFmA attained cis-configuration. This isomerization also involved the maleic acid moiety. CLEFmA was stable in plasma from which it could be efficiently extracted by an acetonitrile precipitation method. These results indicate that CLEFmA is sensitive to hydrolytic cleavage at its maleic acid moiety, and it is recommended that its samples should be stored under refrigerated and light-free conditions, and under inert environment.

关键词： CLEFmA HPLC Stability Shelf-life Isomerization

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Three-year outcomes of patients with non-valvular atrial fibrillation: the COOL-AF registry

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Journal of Geriatric Cardiology 2023年第3期20卷 163-173页

作者： Rungroj Krittayaphong Satchana Pumprueg Pontawee Kaewkumdee Ahthit Yindeengam gregory YH Lip Division of Cardiology Department of MedicineFaculty of Medicine Siriraj HospitalMahidol UniversityBangkokThailand Liverpool Centre for Cardiovascular Science University of Liverpool and Liverpool Heart&Chest HospitalLiverpoolUnited Kingdom Department of Clinical medicine Aalborg UniversityAalborgDenmark

BACKGROUND Clinical outcomes of patients with non-valvular atrial fibrillation(AF)in Asian populations may be different from *** this study,we aimed to determine the incidence of ischemic stroke/systemic embolism(SSE),major bleeding,and death,and the predictors for clinical outcomes in a contemporary Asian cohort of newly diagnosed AF *** This is a prospective multicenter nationwide registry of patients with AF from 27 hospitals in *** data and follow-up data were collected every 6 months until 3 *** collections included demographic,medical history,laboratory,and medication *** outcomes were SSE,major bleeding,and all-cause *** rates for each clinical outcome were calculated and presented as rate per 100 *** and multivariate analysis was performed to determine the independent predictors for clinical *** There was a total of 3405 patients:mean age was 67.8±11.3 years,1981(58.2%)were *** 30.8±9.7 months follow-up,there was a total of 132 SSE(3.9%),191 major bleeding(5.6%),and 357 all-cause deaths(10.5%).The incidence rates of SSE,major bleeding,and death were 1.56(1.30-1.84),2.26(1.96-2.61),and 4.17(3.33-4.25),per 100 person-years *** predictors for clinical outcomes were age,type of AF,and the presence of comorbid *** The incidence rate of SSE,major bleeding,and death remains high reflecting the unmet needs in AF management。

关键词： patients fibrillation mortality

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Pre-implantation exogenous progesterone and pregnancy in *** on fetalplacental development and nutrient transporters in late pregnancy

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Journal of Animal Science and Biotechnology 2021年第3期12卷 952-971页

作者： Katherine m.Halloran Emily C.Hoskins Claire Stenhouse Robyn m.moses Kathrin A.Dunlap m.Carey Satterfield Heewon Seo gregory A.Johnson Guoyao Wu Fuller W.Bazer Department of Animal Science Texas A&M UniversityCollege StationTX 77843-2471USA Department of Veterinary Integrative Biosciences Texas A&M UniversityCollege StationTX 77843USA

Background:Administration of progesterone(P4)to ewes during the first 9 to 12 days of pregnancy accelerates blastocyst development by day 12 of pregnancy,likely due to P4-induced up-regulation of key genes in uterine epithelia responsible for secretion and transport of components of histotroph into the uterine *** study determined if acceleration of blastocyst development induced by exogenous P4 during the pre-implantation period affects fetal-placental development on day 125 of *** ewes(n=35)were mated to fertile rams and assigned randomly to receive daily intramuscular injections of either corn oil vehicle(CO,n=18)or 25 mg progesterone in CO(P4,n=17)for the first 8 days of *** ewes were hysterectomized on day 125 of pregnancy and:1)fetal and placental weights and measurements were recorded;2)endometrial and placental tissues were analyzed for the expression of candidate mRNAs involved in nutrient transport and arginine metabolism;and 3)maternal plasma,fetal plasma,allantoic fluid,and amniotic fluid were analyzed for amino acids,agmatine,polyamines,glucose,and ***:Treatment of ewes with exogenous P4 did not alter fetal or placental growth,but increased amounts of aspartate and arginine in allantoic fluid and amniotic fluid,*** that received exogenous P4 had greater expression of mRNAs for SLC7A1,SLC7A2,SLC2A1,AGmAT,and ODC1 in endometria,as well as SLC1A4,SLC2A5,SLC2A8 and ODC1 in *** addition,AZIN2 protein was immunolocalized to uterine luminal and glandular epithelia in P4-treated ewes,whereas AZIN2 localized only to uterine luminal epithelia in CO-treated ***:This study revealed that exogenous P4 administered in early pregnancy influenced expression of selected genes for nutrient transporters and the expression of a protein involved in polyamine synthesis on day 125 of pregnancy,suggesting a‘programming’effect of P4 on gene expression that affected the composition of nutrients in f

关键词： Amino acids Endometrium Fructose Gene expression Glucose Placenta Polyamines Progesterone

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A cluster-randomized trial comparing two SWITCH implementation support strategies for school wellness intervention effectiveness

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Journal of Sport and Health Science 2023年第1期12卷 87-96页

作者： Richard R.Rosenkranz Philip m.Dixon David A.Dzewaltowski Gabriella m.mcLoughlin Joey A.Lee Senlin Chen Spyridoula Vazou Lorraine m.Lanningham-Foster Doug A.Gentile gregory J.Welk Department of Food NutritionDietetics&HealthKansas State UniversityManhattanKS 66506USA Department of Statistics Snedecor HallIowa State UniversityAmesIA 50011-1210USA Department of Health Promotion University of NebraskaOmahaNE 68198-4365USA Implementation Science Center for Cancer Control and Prevention Research Center Brown SchoolWashington University in St.LouisSt.LouisMO 63130USA Division of Public Health Sciences(Department of Surgery) Washington University School of MedicineWashington University in St.LouisSt.LouisMO 63130USA Department of Health Sciences University of Colorado Colorado SpringsColorado SpringsCO 80918USA Department of Kinesiology Iowa State UniversityAmesIA 50011-4008USA Department of Food Science&Human Nutrition Iowa State UniversityAmesIA 50011USA Department of Psychology Iowa State UniversityAmesIA 50011-1041USA

Background:The School Wellness Integration Targeting Child Health(SWITCH)intervention has demonstrated feasibility as an implementation approach to help schools facilitate changes in students’physical activity(PA),sedentary screen time(SST),and dietary intake(DI).This study evaluated the comparative effectiveness of enhanced(individualized)implementation and standard(group-based)***:Twenty-two Iowa elementary schools participated,with each receiving standardized training(wellness conference and webinars).Schools were matched within region and randomized to receive either individualized or group implementation *** PA,SST,and DI outcomes of 1097 students were assessed at pre-and post-intervention periods using the Youth Activity *** mixed models evaluated differential change in outcomes by condition,for comparative effectiveness,and by ***:Both implementation conditions led to significant improvements in PA and SST over time(pmprove commensurately(p value range:0.02‒0.05).There were no differential changes between the group and individualized conditions for PA(p=0.51),SST(p=0.19),or DI(p=0.73).There were no differential effects by gender(i.e.,non-significant condition-by-gender interactions)for PA(p_(for interaction)=0.86),SST(p_(for interaction)=0.46),or DI(p_(for interaction)=0.15).Effect sizes for both conditions equated to approximately 6 min more PA per day and approximately 3 min less sedentary ***:The observed lack of difference in outcomes suggests that group implementation of SWITCH is equally effective as individualized implementation for building capacity in school wellness ***,the lack of interaction by gender suggests that SWITCH can be beneficial for both boys and *** research is needed to understand the school-level factors that influence implementation(and outcomes)of SWITCH.

关键词： Children Implementation science Obesity prevention Physical activity School health

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Interactions of primary neuroepithelial progenitor and brain endothelial cells: distinct effect on neural progenitor maintenance and differentiation by soluble factors and direct contact

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Cell Research 2007年第7期17卷 619-626页

作者： miguel A Gama Sosa Rita De Gasperi Anne B Rocher Gissel m Perez Keila Simons Daniel E Cruz Patrick R Hof gregory A Elder Departments of Psychiatry Research and Development Service James J. Peters Department of Veterans Affairs Medical Center 130 West Kingsbridge Road Bronx New York 10468 USA Neuroscience Mount Sinai School of Medicine of New York University New York NY Department of Research and Development Service James J. Peters Department of Veterans Affairs Medical Center 130 West Kingsbridge Road Bronx New York 10468 USA

Neurovascular interactions are crucial for the normal development of the central nervous system. To study suchinteractions in primary cultures, we developed a procedure to simultaneously isolate neural progenitor and endothelialcell fractions from embryonic mouse brains. Depending on the culture conditions endothelial cells were found to favormaintenance of the neuroprogenitor phenotype through the production of soluble factors, or to promote neuronal differ-entiation of neural progenitors through direct contact. These apparently opposing effects could reflect differential cellularinteractions needed for the proper development of the brain.

关键词： differentiation culture endothelial cells neuroepithelial cells

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Implementation Regulations for China's Labor Contract Law

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China's Foreign Trade 2008年第Z3期 30-31页

作者： gregory m.Sy Counsel at Grandall Legal Group

*** On January 1,2008,the Labor Contract Law of the People's Republic of China(LCL)became effective,resulting in wide- spread changes in labor policy for all companies and other af- fected *** is the case with legisla... 详细信息

关键词： LCL Implementation Regulations for China’s Labor Contract Law than

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Dietary supplementation with 0.4%L-arginine between days 14 and 30 of gestation enhances NO and polyamine syntheses and water transport in porcine placentae

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Journal of Animal Science and Biotechnology 2023年第2期14卷 627-639页

作者： Cassandra m.Herring Fuller W.Bazer gregory A.Johnson Heewon Seo Shengdi Hu mohammed Elmetwally Wenliang He Daniel B.Long Guoyao Wu Department of Animal Science Texas A&M UniversityCollege StationTX 77843USA Department of Veterinary Integrative Biosciences Texas A&M UniversityCollege StationTX 77843USA.

Background:most embryonic loss in pigs occurs before d 30 of *** supplementation with L-arginine(Arg) during early gestation can enhance the survival and development of conceptuses(embryo/fetus and its extraembryonic membranes) in ***,the underlying mechanisms remain largely ***:Between d 14 and 30 of gestation,each gilt was fed daily 2 kg of a corn-and soybean-meal based diet(12% crude protein) supplemented with either 0.4% Arg(as Arg-HCl) or an isonitrogenous amount of L-alanine(Control).There were 10 gilts per treatment *** d 30 of gestation,gilts were fed either Arg-HCl or L-alanine 30 min before they were hysterectomized,followed by the collection of placentae,embryos,fetal membranes,and fetal *** and allantoic fluids were analyzed for nitrite and nitrate [NOx;stable oxidation products of nitric oxide(NO)],polyamines,and amino *** were analyzed for syntheses of NO and polyamines,water and amino acid transport,concentrations of amino acid-related metabolites,and the expression of angiogenic factors and aquaporins(AQPs).Results:Compared to the control group,Arg supplementation increased(P mber of viable fetuses by 1.9 per litter,the number and diameter of placental blood vessels(+ 25.9% and + 17.0% respectively),embryonic survival(+ 18.5%),total placental weight(+ 36.5%),the total weight of viable fetuses(+ 33.5%),fetal crown-to-rump length(+ 4.7%),and total allantoic and amniotic fluid volumes(+ 44.6% and + 75.5% respectively).Compared to control gilts,Arg supplementation increased(P mines(+ 28.9%);placental concentrations of NOx(+ 22.5%),tetrahydrobiopterin(+ 21.1%),polyamines(+ 20.4%),c AmP(+ 27.7%),and c GmP(+ 24.7%);total amounts of NOx(+ 61.7% to + 96.8%),polyamines(+ 60.7% to + 88.7%),amino acids(+ 39% to + 118%),glucose(+ 60.5% to + 62.6

关键词： Angiogenesis Arginine Fetus Placenta Reproduction

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BET inhibition prevents aberrant RUNX1 and ERG transcription in STAG2 mutant leukaemia cells

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Journal of molecular Cell Biology 2020年第5期12卷 397-399页

作者： Jisha Antony gregory Gimenez Terry Taylor Umaima Khatoon Robert Day Ian mmorison Julia AHorsfield Department of Pathology Dunedin School of MedicineUniversity of OtagoDunedin 9016New Zealand maurice Wilkins Centre for molecular Biodiscovery The University of AucklandPrivate Bag 92019AucklandNew Zealand Southern Community Laboratories Dunedin 9016New Zealand Department of Biochemistry University of OtagoDunedin 9054New Zealand

Cohesin is a multiprotein complex that not only is essential for cell division but also has key roles in genome organization that underpin its gene regulatory *** mutations of genes encoding cohesin subunits occur in myeloid malignancies at 10%–12%(Kon et al.,2013),and the frequency of cohesin mutation in Down syndrome-associated megakaryoblastic leukaemia is even higher(~50%)(Yoshida et al.,2013).Cohesin insufficiency reinforces stem cell programmes and impairs differentiation in haematopoietic stem cells(mazumdar et al.,2015;mullenders et al.,2015;Viny et al.,2015).The STAG2 subunit of cohesin is the most frequently mutated in myeloid malignancies(Kon et al.,2013).In contrast to other cohesin subunits,complete loss of STAG2 is tolerated due to partial compensation by ***2 and STAG1 have redundant roles in cell division(Benedetti et al.,2017;van der Lelij et al.,2017).However,cohesin-STAG1 and cohesin-STAG2 have non-redundant roles in facilitating 3D genome organization to delineate tissue-specific gene expression(Kojic et al.,2018).

关键词： function. redundant

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SYNTHESIS AND POLYmERIZATION OF OLIGO (OXYETHYLENE) mACROmONOmER

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Chinese Journal of Polymer Science 1993年第3期11卷 262-266页

作者：张升水刘庆国杨蕾玲 FARRINGTON gregory C. Laboratory of Solid State Ionics University of Science and Technology Beijing Beijing 100083 Beijing Research Institute of Chemical Industry Beijing 100013 Department of materials Science and Engineering University of Pennsylvania Philadelphia PA 19104 USA.

This paper reports the synthesis of methoxyoligo (oxyethylene) methacrylate (mEO_n , n is the repeating unit number of (CH_2CH_2O) in the macromonomer), and its polymerization in different solvents. mEO_n is prepared through such two independent reactions as (1) anionic polymerization of oxirane initiated by potassium alkoxide and (2) end-capping of methoxy oligo(oxyethylene) by methacrylic group. The n value can be conveniently controlled over the range of 5 ～ 30 by varying the molar ratio of oxirane to initiator and the molecular weight distribution of mEO_n be narrowed by increasing reaction time only in step (1). mEO_n thus obtained shows a rapid polymerization in water and benzene respectively, and both give water-soluble polymers as long as suitable conditions are used.

关键词： m acromonomer Oligo (oxyethylene) Amphiphilic monomer Free-radical Polymerization

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