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Effect of Aspergillus niger prolyl endopeptidase in patients with celiac disease on a long-term gluten-free diet

World Journal of Gastroenterology 2024年第11期30卷 1545-1555页

作者： Juan Pablo Stefanolo Verónica Segura Martina Grizzuti Abel Heredia Isabel Comino ana florencia costa Roberto Puebla María Paz Temprano Sonia Isabel Niveloni Gabriel de Diego María E Oregui Edgardo Gustavo Smecuol Mauricio C de Marzi Elena F Verdú Carolina Sousa Julio César Bai Small Bowel Section Department of MedicineGastroenterology Hospital of Buenos Aires“Dr.C.Bonorino Udaondo”Buenos Aires 1264Argentina Department of Microbiology and Parasitology Faculty of PharmacyUniversity of SevilleSeville 41080Spain Department of Medicine Dr.C.Bonorino Udaondo Gastroenterology HospitalBuenos Aires 1264Argentina Basic and Applied Research Group in Immunology and Bioactives(GIBAIB) Institute of Ecology and Sustainable Development(INEDES)National University of LujanLuján 6700Buenos AiresArgentina Department of Medicine Farncombe Family Digestive Health Research InstituteMcMaster UniversityHamilton L8S 4L8OntarioCanada Facultad de Medicina Universidad del SalvadorBuenos Aires C1051ABBArgentina

BACKGROUND The gluten-free diet(GFD)has limitations,and there is intense research in the development of adjuvant *** To examine the effects of orally administered Aspergillus niger prolyl endopeptidase protease(AN-PEP)on inadvertent gluten exposure and symptom prevention in adult celiac disease(CeD)patients following their usual *** This was an exploratory,double-blind,randomized,placebo-controlled trial that enrolled CeD patients on a long-term *** a 4-wk run-in period,patients were randomized to 4 wk of two AN-PEP capsules(GliadinX;AVI Research,LLC,United States)at each of three meals per day or *** endpoints were:(1)Average weekly stool gluten immunogenic peptides(GIP)between the run-in and end of treatments and between AN-PEP and placebo;(2)celiac symptom index(CSI);(3)CeD-specific serology;and(4)quality of *** samples were collected for GIP testing by ELISA every Tuesday and Friday during run-ins and *** Forty patients were randomized for the intention-to-treat analysis,and three were excluded from the per-protocol ***,628/640(98.1%)stool samples were *** was undetectable(0.32μg/g)to potentially cause mucosal *** GIP concentration in the AN-PEP arm was 44.7%lower than in the run-in ***-third of patients exhibiting GIP>0.08μg/g during run-in had lower or undetectable GIP after AN-PEP *** with the run-in period,the proportion of symptomatic patients(CSI>38)in the AN-PEP arm was significantly lower(P<0.03).AN-PEP did not result in changes in specific *** This exploratory study conducted in a real-life setting revealed high adherence to the *** AN-PEP treatment did not significantly reduce the overall GIP stool ***,given the observation of a significantly lower prevale

关键词： Celiac disease Aspergillus niger prolyl endoprotease Gluten immunogenic peptides Trial Symptoms Real-life trial

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Gluten immunogenic peptide excretion detects dietary transgressions in treated celiac disease patients

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World Journal of Gastroenterology 2019年第11期25卷 1409-1420页

作者： ana florencia costa Emilia Sugai María de la Paz Temprano Sonia Isabel Niveloni Horacio Vázquez María Laura Moreno M.Remedios Domínguez-Flores Alba Mu?oz-Suano Edgardo Smecuol Juan Pablo Stefanolo Andrea F González Angel Cebolla-Ramirez Eduardo Mauri?o Elena F Verdú Julio César Bai Small Bowel Section Department of MedicineDr.C.Bonorino Udaondo Gastroenterology HospitalBuenos Aires 1263Argentina Department of Immunology Biomedal S.L.Sevilla 41092Spain Farncombe Family Digestive Health Research Institute McMaster UniversityHamiltonON L8S4L8Canada Research Institutes Universidad del SalvadorBuenos Aires 1050Argentina

BACKGROUND Life-long removal of gluten from the diet is currently the only way to manage celiac disease(CeD). Until now, no objective test has proven useful to objectively detect ingested gluten in clinical practice. Recently, tests that determine consumption of gluten by assessing excretion of gluten immunogenic peptides(GIP) in stool and urine have been developed. Their utility, in comparison with conventional dietary and analytical follow-up strategies, has not been fully *** To assess the performance of enzyme-linked immunosorbent assay(ELISA) and point-of-care tests(PoCTs) for GIP excretion in CeD patients on gluten-free diet(GFD).METHODS We conducted an observational, prospective, cross-sectional study in patients following a GFD for at least two years. Using the Gastrointestinal Symptom Rating Scale questionnaire, patients were classified at enrollment as asymptomatic or symptomatic. Gluten consumption was assessed twice by 3-d dietary recall and GIP excretion(by ELISA in stool and PoCTs(commercial kits for stool and urine) in two consecutive samples. These samples and dietary reports were obtained 10 day apart one from the other. Patients were encouraged to follow their usual GFD during the study *** Forty-four patients were enrolled, of which 19(43.2%) were symptomatic despite being on a GFD. Overall, 83 sets of stool and/or urine samples were *** out of 44 patients(25.0%) had at least one positive GIP test. The occurrence of at least one positive test was 32% in asymptomatic patients compared with 15.8% in symptomatic patients. GIP was concordant with dietary reports in 65.9% of cases(Cohen′s kappa: 0.317). PoCT detected dietary indiscretions. Both ELISA and PoCT in stool were concordant(concomitantly positive or negative) in 67 out of 74(90.5%) samples. Excretion of GIP was detected in 7(8.4%) stool and/or urine samples from patients considered to be strictly compliant with the GFD by dietary *** GIP dete

关键词： Celiac disease Follow-up Gluten-free diet Gluten immunogenic peptide excretion Rapid tests

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Subterranean termites （Isoptera： Rhinotermitidae）： Exploitation of equivalent food resources with different forms of placement

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Insect Science 2012年第3期19卷 412-418页

作者： Juliana Toledo Lima ana Maria costa-Leonardo Departamento de Biologia Instituto de BiocienciasUNESP-Univ Estadual PaulistaRio Claro-SPBrazil

Coptotermes gestroi and Heterotermes tenuis have been described as important urban pests in Brazil. The establishment of control technologies using baits that consider the social behavior of termites requires a better knowledge of their foraging behavior. Thus, this study analyzed the feeding behavior of these species with three different forms of food placement： food on the surface of a substrate and food either partially or completely buried in the substrate. Experimental arenas were composed of a central chamber connected to three food chambers. Each central chamber contained 550 foragers of C. gestroi or 517 foragers of 11. tenuis. Blocks of Pinus elliottii were placed in the different food chambers. After 28 days, the consumption of each wood block and the percentage of foraging individuals recruited for food chambers were verified in relation to the total survival rate obtained for each one of the 20 replicates. Results showed that completely buried food was most consumed for H. tenuis and presented a higher recruitment rate of workers and soldiers for both species. Although the consumption had non-significant differences for C. gestroi, these termites exhibited a tendency to prefer completely buried food. In these conditions, it can be concluded that the forms of food placement used in the present research influenced the recruitment of individuals for both species. Data also suggests that when the foraging subterranean termites find food resources in the tunneling substrate, they tend to concentrate their efforts on it, a behavior regime that reduces exposure to external environment.

关键词： Coptotermes gestroi feeding behavior foraging behavior Heterotermes tenuis

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Cell membrane and bioactive factors derived from mesenchymal stromal cells: Cell-free based therapy for inflammatory bowel diseases

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World Journal of Stem Cells 2019年第9期11卷 618-633页

作者： Fabiany da costa Goncalves ana Helena Paz Nephrology and Transplantation Internal MedicineErasmus Medical CenterRotterdamGD 3015Netherlands Experimental Research Center Hospital de Clínicas de Porto AlegrePorto AlegreRS 90035-903Brazil

Inflammatory bowel diseases(IBD)are chronic inflammatory disorders of the gastrointestinal tract associated with multifactorial conditions such as ulcerative colitis and Crohn’s *** the underlying mechanisms of IBD remain unclear,growing evidence has shown that dysregulated immune system reactions in genetically susceptible individuals contribute to mucosal ***,conventional treatments have been effective in inducing remission of IBD but not in preventing the relapse of *** this way,mesenchymal stromal cells(MSC)therapy has been recognized as a promising treatment for IBD due to their immunomodulatory properties,ability to differentiate into several tissues,and homing to inflammatory *** so,literature is conflicted regarding the location and persistence of MSC in the body after *** this reason,recent studies have focused on the paracrine effect of the biofactors secreted by MSC,especially in relation to the immunomodulatory potential of soluble factors(cytokines,chemokines,and growth factors)and extracellular vehicles that are involved in cell communication and in the transfer of cellular material,such as proteins,lipids,and nucleic ***,treatment with interferon-γ,tumor necrosis factor-α,and interleukin-1βcauses MSC to express immunomodulatory molecules that mediate the suppression via cell-contact dependent *** together,we present an overview of the role of bioactive factors and cell membrane proteins derived from MSC as a cell-free therapy that can improve IBD treatment.

关键词： Bioactive factors Cell membrane Mesenchymal stem cells Cell-free therapy Inflammatory bowel diseases

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An illustrated checklist of macrofaunal molluscs from soft-sediments of the Abrolhos Parcel(northeastern,Brazil)with 15 new records

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Journal of Oceanology and Limnology 2021年第2期39卷 671-682页

作者： Flávia Maria Pereira da costa ana Maria Setubal PIRES-VANIN Departamento de Oceanografi a Biológica Instituto Oceanográfi coUniversidade de São PauloSão Paulo 05508-120Brazil

Comprehensive understanding of marine biodiversity is essential for conservation,especially for vulnerable *** this paper,we implemented and illustrated a checklist of molluscs from the Abrolhos Parcel,Brazil,the most important coralline area in South Atlantic *** list features 100 species belonging to 4 classes and 85 genera,of which 15 are new records for Bahia State,northeast *** results highlight the potential for new records in the *** species came from 54 unconsolidated sediment samples collected from the bottom of the reef with a 0.042-m^(2) van Veen *** the listed species,Curveulima sp.,Notarchus *** Guyanella clenchi are new records for the South Atlantic,while Caecum metamorphosicum,Eratoidea janeiroensis,Volvarina serrei,Solemya notialis,Solariorbis shimeri,and Amphithalamus glabrus are endemic to Brazilian waters.A comparison of our results with those obtained in other reef environments indicates that the Abrolhos Parcel has a rich malacofauna and suggests that many more species can still be found with more samplings.

关键词： Bivalvia Gastropoda micromolluscs Scaphopoda Solenogastres southwest Atlantic

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Parkinson's Disease:A Multisystem Disorder

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Neuroscience Bulletin 2023年第1期39卷 113-124页

作者： Helena Nunes costa ana Raquel Esteves Nuno Empadinhas Sandra Morais Cardoso CNC–Center for Neuroscience and Cell Biology and CIBB–Center for Innovative Biomedicine and Biotechnology University of Coimbra3004-504CoimbraPortugal IIIUC–Institute for Interdisciplinary Research University of Coimbra3004-504CoimbraPortugal Faculty of Medicine University of Coimbra3004-504CoimbraPortugal

The way sporadic Parkinson's disease(PD)is perceived has undergone drastic changes in recent *** a long time,PD was considered a brain disease characterized by motor disturbances;however,the identification of several risk factors and the hypothesis that PD has a gastrointestinal onset have shed additional ***,after recognition of prodromal non-motor symptoms and the pathological processes driving their evolution,there is a greater understanding of the involvement of other organ *** this reason,PD is increasingly seen as a multiorgan and multisystemic pathology that arises from the interaction of susceptible genetic factors with a challenging environment during aging-related decline.

关键词： Parkinson's disease Gut microbiome Intestinal barrier α-Synuclein Blood-brain barrier

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The brain as a source and a target of prolactin in mammals

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Neural Regeneration Research 2022年第8期17卷 1695-1702页

作者： ana R.costa-Brito Isabel Gonçalves Cecília R.A.Santos CICS-UBI-Health Sciences Research Centre Universidade da Beira InteriorCovilhãPortugal C4-UBI-Cloud Computing Competence Centre Universidade da Beira InteriorCovilhãPortugal

Prolactin is a polypeptide hormone associated with an extensive variety of biological *** the roles of prolactin in vertebrates,some were preserved throughout *** is the case of its function in the brain,where prolactin receptors,are expressed in different structures of the central nervous *** the brain,prolactin actions are principally associated with reproduction and parental behavior,and involves the modulation of adult neurogenesis,neuroprotection,and neuroplasticity,especially during pregnancy,thereby preparing the brain to *** is mainly produced by specialized cells in the anterior pituitary ***,during vertebrate evolution many other extrapituitary tissues do also produce prolactin,like the immune system,endothelial cells,reproductive structures and in several regions of the *** review summarizes the relevance of prolactin for brain function,the sources of prolactin in the central nervous system,as well as its local production and secretion.A highlight on the impact of prolactin in human neurological diseases is also provided.

关键词： brain brain disease choroid plexus neurogenesis neuroplasticity neuroprotection prolactin prolactin receptor

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Association between EGF +61A/G polymorphism and gastric cancer in Caucasians

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World Journal of Gastroenterology 2011年第4期17卷 488-492页

作者： ana Paula Araújo Bruno M costa ana L Pinto-Correia Maria Fragoso Paula Ferreira Mário Dinis-Ribeiro Sandra costa Rui M Reis Rui Medeiros Molecular Oncology Group Portuguese Institute of Oncology of Porto Life and Health Sciences Research Institute (ICVS) School of Health Sciences Oncology Department Portuguese Institute of Oncology of Porto Gastroenterology Department Portuguese Institute of Oncology of Porto Portugal Cintesis/Faculty of Medicine University of Porto Centro de Estudos em Biomedicina Health Sciences Faculty-Fernando Pessoa University Instituto de Ciencias Biomédicas de Abel Salazar Abel Salazar Institute for the Biomedical Sciences

AIM: To investigate the association between epidermal growth factor (EGF) +61A/G polymorphism and susceptibility to gastric cancer, through a cross-sectional study. METHODS: Polymerase chain reaction resctriction fragment lenght polymorphism analyses were used to genotype EGF +61 in 207 patients with gastric lesions (162 patients with gastric adenocarcinomas, 45 with atrophy or intestinal metaplasia) and 984 controls. All subjects were Caucasian. RESULTS: Genotype distribution was 23.5% for GG and 76.5% for GA/AA in the control group, 18.4% for GG and 68.6% for GA/AA in the entire group with gastric lesions and 17.9% for GG and 82.1% for GA/AA in the group with gastric adenocarcinoma. No statistically significant associations were found between EGF +61 variants and risk for developing gastric cancer [odds ratios (OR) = 1.41, 95% confidence intervals (CI): 0.90-2.21, P = 0.116]. However, the stratification of individuals by gender revealed that males carrying A alleles (EGF +61A/G or AA) had an increased risk for developing gastric cancer as compared to GG homozygous males (OR = 1.55, 95% CI: 1.05-2.28, P = 0.021). CONCLUSION: In summary, we found that males who were A carriers for EGF +61 had an increased risk for developing gastric cancer. This result may be explained by the suggestion that women secrete less gastric acid than men.

关键词： Epidermal growth factor polymorphism Epidermal growth factor receptor Gastric cancer

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“Love Is Strong, and You＇re so Sweet”： JAGGER Is Essential for Persistent Synergid Degeneration and Polytubey Block in Arabidopsis thaliana

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Molecular Plant 2016年第4期9卷 601-614页

作者： ana Marta Pereira Margarida Sofia Nobre Sara Cristina Pinto ana Lucia Lopes Mario Luis costa Simona Masiero Silvia Coimbra Departamento de Biologia Faculdade de Ciencias da Universidade do Porto Rua do Campo Alegre 4169-007 Porto Portugal Plant Functional Genomics Group Biosystems and Integrative Sciences Institute (BiolSI) 4169-007 Porto Portugal Dipartimento di BioScienze Universita degli Studi di Milano 20133 Milan Italy Present address: Institute of Plant Biology and ZUrich-Basel Plant Science Center University of ZUrich Zolikerstrasse 107 8008 Zurich Switzerland

Successful double fertilization and subsequent seed development in flowering plants requires the delivery of two sperm cells, transported by a pollen tube, into the embryo sac of an ovule. The embryo sac cells tightly control synergid cell death, and as a result the polyspermy block. Arabinogalactan proteins are highly glycosylated proteins thought to be involved in several steps of the reproductive process. We show that JAGGER, Arabinogalactan Protein 4, is an important molecule necessary to prevent the growth of multiple pollen tubes into one embryo sac in Arabidopsis thaliana. In jagger, an AGP4 knockout mutant, the pistils show impaired pollen tube blockage as a consequence of the survival of the persistent synergid. JAGGER seems to be involved in the signaling pathway that leads to a blockage of pollen tube attraction. Our results shed light on the mechanism responsible for preventing polyspermy in Arabidopsis and for safe- guarding successful fertilization of all ovules in one pistil, ensuring seed set and the next generation.

关键词： Polytubey persistent synergid arabinogalactan proteins polyspermy

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Effects of living and metabolically inactive mesenchymal stromal cells and their derivatives on monocytes and macrophages

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World Journal of Stem Cells 2021年第9期13卷 1160-1176页

作者： Alexia Nedel Sant'ana Anelise Bergmann Araújo Fabiany da costa Gonçalves ana Helena Paz Laboratório de Células Tecidos e Genes Hospital de Clínicas de Porto AlegrePorto Alegre 90035-903RSBrazil Centro de Processamento Celular Hospital de Clínicas de Porto AlegrePorto Alegre 90035-903RSBrazil Department of Internal Medicine Erasmus Medical CenterRotterdam 3015 GDNetherlands Departamento de Ciências Morfológicas Instituto de Ciências Básicas da SaúdeUniversidade Federal do Rio Grande do SulPorto Alegre 90035-903RSBrazil

Mesenchymal stromal cells (MSCs) are multipotent and self-renewing stem cellsthat have great potential as cell therapy for autoimmune and inflammatorydisorders, as well as for other clinical conditions, due to their immunoregulatoryand regenerative properties. MSCs modulate the inflammatory milieu by releasingsoluble factors and acting through cell-to-cell mechanisms. MSCs switch theclassical inflammatory status of monocytes and macrophages towards a nonclassicaland anti-inflammatory phenotype. This is characterized by an increasedsecretion of anti-inflammatory cytokines, a decreased release of pro-inflammatorycytokines, and changes in the expression of cell membrane molecules and inmetabolic pathways. The MSC modulation of monocyte and macrophage phenotypesseems to be critical for therapy effectiveness in several disease models, sincewhen these cells are depleted, no immunoregulatory effects are observed. Here,we review the effects of living MSCs (metabolically active cells) and metabolicallyinactive MSCs (dead cells that lost metabolic activity by induced inactivation) andtheir derivatives (extracellular vesicles, soluble factors, extracts, and microparticles)on the profile of macrophages and monocytes and the implications forimmunoregulatory and reparative processes. This review includes mechanisms ofaction exhibited in these different therapeutic appro-aches, which induce the antiinflammatoryproperties of monocytes and macrophages. Finally, we overviewseveral possibilities of therapeutic applications of these cells and their derivatives,with results regarding monocytes and macrophages in animal model studies andsome clinical trials.

关键词： Mesenchymal stromal cells Macrophage Monocyte Immunomodulation Cell therapy Immunoregulation

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