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Mucosal healing and inflammatory bowel disease:Therapeutic implications and new targets

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World Journal of Gastroenterology 2023年第7期29卷 1157-1172页

作者： Megan Lynn Otte Raju Lama Tamang julia Papapanagiotou Rizwan Ahmad Punita Dhawan Amar b Singh Department of Pathology and Microbiology University of Nebraska Medical CenterOmahaNE 68198United States Department of biochemistry and Molecular biology University of Nebraska Medical CenterOmahaNE 68198United States

Mucosal healing(MH)is vital in maintaining homeostasis within the gut and protecting against injury and *** factors and signaling pathways contribute in a dynamic and coordinated manner to maintain intestinal homeostasis and mucosal regeneration/***,when intestinal homeostasis becomes chronically disturbed and an inflammatory immune response is constitutively active due to impairment of the intestinal epithelial barrier autoimmune disease results,particularly inflammatory bowel disease(IbD).Many proteins and signaling pathways become dysregulated or impaired during these pathological conditions,with the mechanisms of regulation just beginning to be ***,there remains a relative lack of broadly effective therapeutics that can restore MH due to the complexity of both the disease and healing processes,so tissue damage in the gastrointestinal tract of patients,even those in clinical remission,*** increased understanding of the molecular mechanisms of IbD and MH,tissue damage from autoimmune disease may in the future be ameliorated by developing therapeutics that enhance the body’s own healing *** this review,we introduce the concept of mucosal healing and its relevance in IbD as well as discuss the mechanisms of IbD and potential strategies for altering these processes and inducing MH.

关键词： Inflammation Injury/repair Mucosal healing Mucosal barrier Therapeutics Colitis

broadband mechanoresponsive liquid metal sensors

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npj Flexible Electronics 2022年第1期6卷 718-725页

作者： Md Saifur Rahman julia E.Huddy Andrew b.Hamlin William J.Scheideler Thayer School of Engineering Dartmouth CollegeHanoverNH 03755USA

Stretchable electronics have the fundamental advantage of matching the complex geometries of the human body,providing opportunities for real-time biomechanical *** report a method for high-frequency AC-enhanced resistive sensing that leverages deformable liquid metals to improve low-power detection of mechanical stimuli in wearable *** fundamental mechanism of this enhancement is geometrical modulation of the skin effect,which induces current crowding at the surface of a liquid metal *** combination with DC sensing,this method quantitatively pinpoints mechanical modes of deformation such as stretching in-plane and compression out-of-plane that are traditionally impossible to *** we explore this method by finite element simulations then employ it in a glove to detect hand gestures and tactile forces as well as a respiratory sensor to measure ***,this AC sensor uses lower power(100X)than DC sensors,enabling a new generation of energy-efficient wearables for haptics and biomedical sensing.

关键词： wear deformation liquid

Impact of mine waters on chemical composition of soil in the Partizansk Coal basin, Russia

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International Soil and Water Conservation Research 2019年第1期7卷 57-63页

作者： Ola Arefieva Alina V.Nazarkina Natalya V.Gruschakova julia E.Skurikhina Vera b.Kolycheva Far Eastern federal University 8Sukhanova str.690950VladivostokRussian Federation Institute of biology and Soil Science Far-Eastern BranchRussian Academy of Sciences159Stoletia prospect690022 VladivostokRussian Federation Pacific State Medical University 2Ostryakov Avenue690002VladivostokRussian Federation

Partizansk Coal basin,located in the south of the Russian Far Eastern Region,was intensively mined from 1918 until *** it was mostly explored by underground excavation,the natural landscapes were transformed into anthropogenic *** the mines closed,ground subsidence occurred widely,especially in areas near the waste *** caused water tables to rise to the surface and pollute the *** of the hydrochemical composition of the mine waters were conducted in 2011-2013,and showed low alkalinity and average level of *** can be explained by the fact that while going up through soil mass,the mine waters lost their much of their pollutants due to soil buffering All mine water samples contain thermo-tolerant coliform bacteria *** that indicates a source of fresh fecal *** research indicates increased hydrocarbon ion concentrations in mine waters,especially in autumn,that resulted in accumulation of chromium and copper compounds,which can cause soil pollution.A strong relationship between the chemical composition of the mine waters and soil extracts was found within areas of unregulated groundwater discharge on the *** negative correlation between pH and content of metal compounds including chromium and copper was found at the 'Avangard' mine (r =-0.95);and between alkalinity and chromium content at the 'Glubokaya' mine (r =-0.94).

关键词： Mine waters Soil solution Chemical composition Abandoned coal mines bacteriological contamination of water

Association between calcium sensing receptor gene polymorphisms and chronic pancreatitis in a US population:Role of serine protease inhibitor Kazal 1type and alcohol

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World Journal of Gastroenterology 2008年第28期14卷 4486-4491页

作者： Venkata Muddana Janette Lamb julia b Greer beth Elinoff Robert H Hawes Peter b Cotton Michelle A Anderson Randall E brand Adam Slivka David C Whitcomb Division of Gastroenterology Hepatology and NutritionDepartment of MedicineUniversity of Pittsburgh Medical CenterPittsburgh PA 15213United States Digestive Disorder Center Medical University of South CarolinaCharleston SC 29403United States Department of Medicine University of Michigan Medical CenterAnn Arbor MI 48109United States Department of medicine Northwestern Universityand Currently at University of Pittsburgh Medical CenterPittsburgh PA 15213United States Division of Gastroenterology Hepatology and NutritionDepartment of MedicineUniversity of Pittsburgh Medical CenterPittsburgh PA 15213United States Department of Human GeneticsUniversity of PittsburghPittsburgh PA 15213United States

AIM： To test the hypothesis that calcium sensing receptor （CASR） polymorphisms are associated with chronic pancreatitis （CP）, and to determine whether serine protease inhibitor Kazal 1type （SPINK1） N34S or alcohol are necessary co-factors in its etiology. METHODS： Initially, 115 subjects with pancreatitis and 66 controls were evaluated, of whom 57 patients and 21 controls were predetermined to carry the high-risk SPINK1 N34S polymorphism. We sequenced CASR gene exons 2, 3, 4, 5 and 7, areas containing the majority of reported polymorphisms and novel mutations. based on the initial results, we added 223 patients and 239 controls to analyze three common nonsynonymous single nucleotide polymorphisms （SNPs） in exon 7 （A986S, R990G, and Q1011E）. RESULTS： The CASR exon 7 R990G polyrnorphism was significantly associated with CP （OR, 2.01; 95% CI, 1.12-3.59; P = 0.015）. The association between CASR R990G and CP was stronger in subjects who reported moderate or heavy alcohol consumption （OR, 3.12; 95% CI, 1.14-9.13; P = 0.018）. There was no association between the various CASR genotypes and SPINK1 N34S in pancreatitis. None of the novel CASR polymorphisms reported from Germany and India was detected. CONCLUSION： Our United States-based study confirmed an association of CASR and CP and for the first time demonstrated that CASR R990G is a significant risk factor for CP. We also conclude that the risk of CP with CASR R990G is increased in subjects with moderate to heavy alcohol consumption.

关键词： Calcium sensing receptor Serine protease inhibitor Kazal llype Chronic pancreatitis Alcohol

A review of physicochemical and biological contaminants in drinking water and their impacts on human health

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Water Science and Engineering 2023年第4期16卷 333-344页

作者： Ahsan Shah Arun Arjunan Ahmad baroutaji julia Zakharova School of Engineering Computing and Mathematical SciencesUniversity of WolverhamptonWolverhamptonWV11LYUnited Kingdom School of Engineering and Applied Science Aston UniversityAston TriangleBirminghamB47ETUnited Kingdom School of Architecture and built Environment University of WolverhamptonWolverhamptonWV11LYUnited Kingdom

Clean drinking water is one of the United Nations Sustainable Development *** significant progress in the water purification technology,many regions still lack access to clean *** paper provides a review of selected water contaminants and their impacts on human *** World Health Organization(WHO)guidelines and regional standards for key contaminants were used to characterise water quality in the European Union and *** concept of safe drinking water was explained based on the non-observed adverse effect level,threshold concentrations for toxic chemicals,and their total daily *** techniques for monitoring water contaminants and the drinking water standards from five different countries,including the UK,USA,Canada,Pakistan and India,were compared to WHO recommended *** literature on actual water quality in these regions and its potential health impacts was also ***,the role of public water suppliers in identifying and monitoring drinking water contaminants in selected developed countries was presented as a potential guideline for developing *** review emphasised the need for a comprehensive understanding of water quality and its impacts on human health to ensure access to clean drinking water worldwide.

关键词： Drinking water contaminants Physicochemical contaminants biological contaminants Human health risks Waterborne diseases Water quality Public health concerns Water treatment

Significant association between AbO blood group and pancreatic cancer

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World Journal of Gastroenterology 2010年第44期16卷 5588-5591页

作者： julia b Greer Mark H Yazer Jay S Raval M Michael barmada Randall E brand David C Whitcomb Department of Medicine Division of GastroenterologyHepatology and NutritionUniversity of Pittsburgh School of Medicine Department of Pathology University of Pittsburgh School of Medicine The Institute for Transfusion Medicine Department of Human Genetics Graduate School of Public HealthUniversity of Pittsburgh University of Pittsburgh Cancer Institute

AIM:To evaluate whether the AbO blood group is related to pancreatic cancer risk in the general population of the United ***:Using the University of Pittsburgh's clinicalpancreatic cancer registry,the blood donor database from our local blood bank (Central blood bank),and the blood product recipient database from the regional transfusion service (Centralized Transfusion Service) in Pittsburgh,Pennsylvania,we identified 274 pancreatic cancer patients with previously determined serological AbO blood group *** AbO blood group frequency was compared between these patients and 708842 individual,community-based blood donors who had made donations to Pittsburgh's Central blood bank between 1979 and ***:The frequency of blood group A was statistically significantly higher amongst pancreatic cancer patients compared to its frequency amongst the regional blood donors [47.63% vs 39.10%,odds ratio (OR)=1.43,P=0.004].Conversely,the frequency of blood group O was significantly lower amongst pancreatic cancer patients relative to the community blood donors (32.12% vs 43.99%,OR=0.60,P=0.00007).There were limited blood group b (n=38) and Ab (n=17) pancreatic cancer patients;the overall P trend value comparing patient to donor blood groups was ***:The AbO blood group is associated with pancreatic cancer *** studies should examine the mechanism linking pancreatic cancer risk to AbO blood group.

关键词： AbO blood group Pancreatic adenocarcinoma Surveillance Risk reduction Epidemiology

Characterizing drug-metabolizing enzymes and transporters that are bona fide CAR-target genes in mouse intestine

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Acta Pharmaceutica Sinica b 2016年第5期6卷 475-491页

作者： Shinhee Park Sunny Lihua Cheng julia Yue Cui Department of Environmental and Occupational Health Sciences University of Washington

Intestine is responsible for the biotransformation of many orally-exposed *** constitutive androstane receptor(CAR/Nr1i3) is known to up-regulate many genes encoding drugmetabolizing enzymes and transporters(drug-processing genes/DPGs) in liver,but less is known regarding its effect in ***-day-old wild-type and Car / mice were administered the CARligand TCPObOP or vehicle once daily for 4 *** wild-type mice,Car m RNA was down-regulated by TCPObOP in liver and *** / mice had altered basal intestinal expression of many DPGs in a section-specific *** with the liver data(Aleksunes and Klaassen,2012),TCPObOP upregulated many DPGs(Cyp2b10,Cyp3a11,Aldh1a1,Aldh1a7,Gsta1,Gsta4,Gstm1-m4,Gstt1,Ugt1a1,Ugt2b34,Ugt2b36,and Mrp2–4) in specific sections of small intestine in a CAR-dependent ***,the m RNAs of Nqo1 and Papss2 were previously known to be up-regulated by TCPObOP in liver but were not altered in ***,many known CAR-target genes were highest expressed in colon where CAR is minimally expressed,suggesting that additional regulators are involved in regulating their *** conclusion,CAR regulates the basal expression of many DPGs in intestine,and although many hepatic CAR-targeted DPGs were bona fide CAR-targets in intestine,pharmacological activation of CAR in liver and intestine are not identical.

关键词： Drug-processing genes Intestine Mice CAR Drug-metabolizing enzymes Transporters

UV-b Radiation Induces Mu Element Somatic Transposition in Maize

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Molecular Plant 2013年第6期6卷 2004-2007页

作者： julia Questa Virginia Walbot Paula Casati Centro de Estudios Fotosintéticos y bioquímicos (CEFObI) Universidad Nacional de Rosario Rosario Argentina Cell and Developmental biology John Innes Centre Norwich Research Park UK Department of biology Stanford University Stanford CA 94305-5020 USA

Dear Editor, The maize Mutator （MuDRIMu） transposon family is the most active DNA transposon in plants （Lisch, 2002）. The Mu family contains diverse elements, all sharing similar -215-bp terminal inverted repeats （TIRs）. MuDR is the autonomous element, and a transcriptionally active MuDR is required for transposition of the non-autonomous Mu elements （Chomet et al., 1991）. MuDR contains two genes, mudrA and mudrb （Figure 1A）; mudrA encodes the MURA transposase, and mudrb encodes a protein with unknown function. To avoid the deleterious effects of transposons, plants have acquired mechanisms to epigenetically silence them. Silenced Mu ele- ments become heavily methylated, and their reactivation is very rare. To date, only UV-b radiation treatments have reac- tivated silenced Mu （Walbot, 1999）.

关键词： UV-b 元素辐射诱导玉米换位表观遗传学转座子赋值函数

Accelerated tooth movement in Rsk2-deficient mice with impaired cementum formation

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International Journal of Oral Science 2020年第4期12卷 338-345页

作者： Cita Nottmeier Maximilian G.Decker julia Luther Simon von Kroge bärbel Kahl-Nieke Michael Amling Thorsten Schinke julian Petersen Till Koehne Department of Orthodontics University Medical Center Hamburg-EppendorfHamburgGermany Institute of Osteology and biomechanics University Medical Center Hamburg-EppendorfHamburgGermany

Coffin–Lowry–Syndrome(CLS)is a X-linked mental retardation characterized by skeletal dysplasia and premature tooth *** and others have previously demonstrated that the ribosomal S6 kinase RSK2,mutated in CLS,is essential for bone and cementum formation;however,it remains to be established whether RSK2 plays also a role in mechanically induced bone remodeling during orthodontic tooth movement(OTM).We,therefore,performed OTM in wild-type(WT)mice and Rsk2-deficient mice using Nitinol tension springs that were fixed between the upper left molars and the *** untreated contralateral molars served as internal *** 12 days of OTM,the jaws were removed and examined by micro-computed tomography(μCT),decalcified histology,and *** analysis of the untreated teeth confirmed that the periodontal phenotype of Rsk2-deficient mice is characterized by alveolar bone loss and hypoplasia of root *** of OTM usingμCT revealed that OTM was more than two-fold faster in Rsk2-deficient mice as compared to *** also observed that OTM caused alveolar bone loss and root resorptions in WT and Rsk2-deficient ***,quantification of these orthodontic side effects revealed no differences between WT and Rsk2-deficient *** together,Rsk2 loss-of-function accelerates OTM in mice without causing more side effects.

关键词： impaired deficient movement