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P2X7 receptor blockade decreases inflammation,apoptosis,and enteric neuron loss during clostridioides difficile toxin A-induced ileitis in mice

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World Journal of Gastroenterology 2022年第30期28卷 4075-4088页

作者： Ana A Q A Santos Deiziane V S costa Danielle A Foschetti Antoniella S G Duarte conceicao S Martins Pedro M G Soares Patricia castelucci gerly a c.brito Department of Morphology School of MedicineFederal University of CearaFortaleza 60430-170CearaBrazil Department of Physiology and Pharmacology School of MedicineFederal University of CearáFortaleza 60430-170CearaBrazil Department of Pathology and Legal Medicine School of MedicineFederal University of CearaFortaleza 60430-170CearaBrazil Department of Morphology(UFc) Federal University of CearaFortaleza 60430-170CearaBrazil Department of Anatomy Institute of Biomedical SciencesUniversity of São PauloSao Paulo 05508-270Brazil Department of Morphology Federal University of CearaFortaleza 60140-170CearaBrazil

clostridioides difficile(***)is the most common pathogen causing health care-associated *** TcdA and TcdB have been shown to activate enteric neurons;however,what population of these cells is more profoundly influenced and the mechanism underlying these effects remain *** To characterize a specific population of TcdA-affected myenteric neurons and investigate the role of the P2X7 receptor in TcdA-induced ileal inflammation,cell death,and the changes in the enteric nervous system in *** Swiss mice were used to model TcdA-induced ileitis in ileal loops exposed to TcdA(50μg/Loop)for 4 *** investigate the role of the P2X7 receptor,Brilliant Blue G(50 mg/kg,i.p.),which is a nonspecific P2X7 receptor antagonist,or A438079(0.7μg/mouse,i.p.),which is a competitive P2X7 receptor antagonist,were injected one hour prior to TcdA *** samples were collected to analyze the expression of the P2X7 receptor(by quantitative real-time polymerase chain reaction and immunohistochemistry),the population of myenteric enteric neurons(immunofluorescence),histological damage,intestinal inflammation,cell death(terminal deoxynucleotidyltransferasemediated dUTP-biotin nick end labeling),neuronal loss,and S100B synthesis(immunohistochemistry).RESULTS TcdA upregulated(Pceptor gene in the ileal tissues,increasing the level of this receptor in myenteric neurons compared to that in control *** with the control mice indicated that TcdA promoted(Pc calretinin+(calr)and choline acetyltransferase+neurons and increased the number of nitrergic+and calr+neurons expressing the P2X7 *** of the P2X7 receptor decreased TcdAinduced intestinal damage,cytokine release[interleukin(IL)-1β,IL-6,IL-8,and tumor necrosis factor-α],cell death,enteric neuron loss,and S100B synthesis in the mouse *** Our findings demonstrated that TcdA induced the upregulation of the P

关键词： clostridioides difficile clostridioides difficile toxin A P2X7 receptor Enteric nervous system Enteric neuron Enteric glia

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Gut-microbiome-brain axis:the crosstalk between the vagus nerve,alpha-synuclein and the brain in Parkinson's disease

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Neural Regeneration Research 2023年第12期18卷 2611-2614页

作者： Júlio césar claudino dos Santos Leandro Freitas Oliveira Felipe Micelli Noleto camilla Teixeira Pinheiro Gusmão gerly Anne de castro brito Glauce Socorro de Barros Viana christus University center-UNIcHRISTUS FortalezaCEBrazil Postgraduate Program in Morphofunctional Sciences Federal University of Ceará-UFCFortalezaCEBrazil Universidade católica de Brasília-UcB BrasíliaDFBrasil Postgraduate Program in Physiology and Pharmacology Department of the Federal University of ceará-UFc FortalezaCEBrazil Physiology and Pharmacology Department of the Federal University of ceará-UFc FortalezaCEBrazil

This critical review of the literature shows that there is a close link between the microbiome,the gut,and the brain in Parkinson's *** vagus nerve,the main component of the parasympathetic nervous system,is involved in the regulation of immune response,digestion,heart rate,and control of *** can detect microbiota metabolites through its afferents,transferring this gut information to the central nervous *** and clinical studies have shown the important role played by the gut microbiome and gut-related factors in disease development and progression,as well as treatment *** findings suggest that the gut microbiome may be a valuable target for new therapeutic strategies for Parkinson's *** studies are needed to better understand the underlying biology and how this axis can be modulated for the patient's benefit.

关键词： alpha-synuclein enteric microbiota gastrointestinal tract Parkinson's disease vagus nerve

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α,β-amyrin, a natural triterpenoid ameliorates L-arginine-induced acute pancreatitis in rats

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World Journal of Gastroenterology 2010年第34期16卷 4272-4280页

作者： caroline Mouro Melo Karine Maria Martins Bezerra carvalho Julliana catharina de Sousa Neves Talita cavalcante Morais Vietla Satyanarayana Rao Flávia Almeida Santos gerly Anne de castro brito Mariana Helena chaves Department of Physiology and Pharmacology Biomedical Institute of Brazilian Semiarid Faculty of Medicine Federal University of Ceará Department of Morphology Faculty of Medicine Federal University of Ceará Department of Organic and Inorganic chemistry Federal University of Piauí

AIM: To study the benef icial effects of triterpene α,β-amyrin and the underlying mechanisms in an experimental pancreatitis model. METHODS: Acute pancreatitis was induced in five groups of rats (n = 8) by L-arginine (2 × 2.5 g/kg, intraperitoneal, 1 h apart) and 1 h later, they received a single oral dose of α,β-amyrin (10, 30 and 100 mg/kg),methylprednisolone (30 mg/kg) and vehicle (3% Tween 80). A saline (0.9% Nacl) treated group served as a normal control. Efficacy was assessed at 24 h by determination of serum levels of amylase, lipase and proinflammatory cytokines [tumor necrosis factor (TNF)-α and interleukin (IL)-6], pancreatic myeloperoxidase (MPO) activity, lipid peroxidation [thiobarbituric acid reactive substances (TBARS)], nitrate/nitrite levels, and the wet weight/body weight ratio. Tissue histology and the immunoreactivity for TNF-α and inducible nitric oxide synthetase (iNOS) were performed. RESULTS: α,β-amyrin and methylprednisolone treatments significantly (P ced increases in pancreatic wet weight/body weight ratio, and decreased the serum levels of amylase and lipase, and TNF-α and IL-6, as compared to the vehicle control. Also, pancreatic levels of MPO activity, TBARS, and nitrate/nitrite were signifi cantly lower. Histological f indings and TNF-α and iNOS immunostaining further confirmed the amelioration of pancreatic injury by α,β-amyrin. cONcLUSION: α,β-amyrin has the potential to combat acute pancreatitis by acting as an anti-in? ammatory and antioxidant agent.

关键词： Acute pancreatitis L-arginine cytokines Lipid peroxidation α,β-amyrin

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