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1.
Int Immunopharmacol ; 136: 112316, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-38823183

RESUMEN

The objective of this study was to investigate the neuroimmune mechanisms implicated in the enhancement of gastrointestinal function through the administration of oral DHA. Mast cell-deficient mice (KitW-sh) and C57BL/6 mice were used to establish postoperative ileus (POI) models. To further validate our findings, we conducted noncontact coculture experiments involving dorsal root ganglion (DRG) cells, bone marrow-derived mast cells (BMMCs) and T84 cells. Furthermore, the results obtained from investigations conducted on animals and cells were subsequently validated through clinical trials. The administration of oral DHA had ameliorative effects on intestinal barrier injury and postoperative ileus. In a mechanistic manner, the anti-inflammatory effect of DHA was achieved through the activation of transient receptor potential ankyrin 1 (TRPA1) on DRG cells, resulting in the stabilization of mast cells and increasing interleukin 10 (IL-10) secretion in mast cells. Furthermore, the activation of the pro-repair WNT1-inducible signaling protein 1 (WISP-1) signaling pathways by mast cell-derived IL-10 resulted in an enhancement of the intestinal barrier integrity. The current study demonstrated that the neuroimmune interaction between mast cells and nerves played a crucial role in the process of oral DHA improving the intestinal barrier integrity of POI, which further triggered the activation of CREB/WISP-1 signaling in intestinal mucosal cells.


Asunto(s)
Ácidos Docosahexaenoicos , Ileus , Interleucina-10 , Mucosa Intestinal , Mastocitos , Ratones Endogámicos C57BL , Complicaciones Posoperatorias , Canal Catiónico TRPA1 , Animales , Mastocitos/efectos de los fármacos , Mastocitos/inmunología , Ácidos Docosahexaenoicos/farmacología , Ácidos Docosahexaenoicos/uso terapéutico , Canal Catiónico TRPA1/metabolismo , Ratones , Ileus/tratamiento farmacológico , Ileus/inmunología , Humanos , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/inmunología , Mucosa Intestinal/patología , Mucosa Intestinal/metabolismo , Masculino , Interleucina-10/metabolismo , Complicaciones Posoperatorias/tratamiento farmacológico , Complicaciones Posoperatorias/inmunología , Ganglios Espinales/metabolismo , Ganglios Espinales/efectos de los fármacos , Modelos Animales de Enfermedad , Técnicas de Cocultivo , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico
2.
Cell Commun Signal ; 21(1): 17, 2023 01 23.
Artículo en Inglés | MEDLINE | ID: mdl-36691021

RESUMEN

BACKGROUND: The inflammatory response induced by intestinal ischaemia‒reperfusion injury (I/R) is closely associated with infectious complications and mortality in critically ill patients, and the timely and effective clearance of apoptotic cells is an important part of reducing the inflammatory response. Studies have shown that the efferocytosis by phagocytes plays an important role. Recently, studies using small intestine organoid models showed that macrophage efferocytosis could promote the repair capacity of the intestinal epithelium. However, no studies have reported efferocytosis in the repair of I/R in animal models. RESULTS: We used an in vivo efferocytosis assay and discovered that macrophage efferocytosis played an indispensable role in repairing and maintaining intestinal barrier function after I/R. In addition, the specific molecular mechanism that induced macrophage efferocytosis was Cth-ERK1/2 dependent. We found that Cth drove macrophage efferocytosis in vivo and in vitro. Overexpression/silencing Cth promoted/inhibited the ERK1/2 pathway, respectively, which in turn affected efferocytosis and mediated intestinal barrier recovery. In addition, we found that the levels of Cth and macrophage efferocytosis were positively correlated with the recovery of intestinal function in clinical patients. CONCLUSION: Cth can activate the ERK1/2 signalling pathway, induce macrophage efferocytosis, and thus promote intestinal barrier repair. Video Abstract.


Asunto(s)
Cistationina gamma-Liasa , Intestinos , Sistema de Señalización de MAP Quinasas , Macrófagos , Animales , Cistationina gamma-Liasa/metabolismo , Macrófagos/metabolismo , Fagocitosis , Transducción de Señal , Humanos , Ratones , Intestinos/lesiones , Intestinos/fisiología
3.
Syst Rev ; 10(1): 17, 2021 01 09.
Artículo en Inglés | MEDLINE | ID: mdl-33419464

RESUMEN

OBJECTIVES: The purpose of this study was to comprehensively assess the heterogeneity of procedures in the diagnostic guidelines for acute pancreatitis and to identify gaps limiting knowledge in diagnosing this disease. METHODS: A systematic search of a number of databases was performed to determine the guidelines for the diagnosis of acute pancreatitis in patients with severe pancreatitis. The guidelines for the diagnosis of severe pancreatitis were evaluated by AGREE II. The Measurement Scale of Rate of Agreement (MSRA) was used to assess the guidelines (2015-2020) and extract evidence supporting these recommendations for analysis. RESULTS: Seven diagnostic guidelines for acute pancreatitis were included. Only the 2019 WSES Guidelines for the Management of Severe Acute Pancreatitis and the Japanese Guidelines for the Management of Acute Pancreatitis: Japanese Guidelines 2015 had a total score of more than 60%, which is worthy of clinical recommendation. The average scores of the Scope and Purpose domain and the Clarity and Expression domain were the highest at 71.62% and 75.59%, respectively, while the average score of the Applicability area was the lowest at 16.67%. The included guidelines were further analyzed to determine the heterogeneity of the diagnosis of acute pancreatitis. The main reasons for the heterogeneity were the citation of low-quality evidence, the presence of far too many indicators for the classification of acute pancreatitis, unclear depictions of the standard, and poorly comprehensive recommendations for the diagnosis of the aetiology in the primary diagnosis of acute pancreatitis, the severity classification, the aetiological diagnosis, and the diagnosis of comorbidities. CONCLUSIONS: The quality of different diagnostic guidelines for severe pancreatitis is uneven. The recommendations are largely based on low-quality evidence, and the guidelines still have much room for improvement to reach a high level of quality. The diagnostic procedures for acute pancreatitis vary widely in different guidelines. There are large differences between them, and resolving the abovementioned reasons would be a very wise choice for guideline developers to revise and upgrade the guidelines in the future.


Asunto(s)
Pancreatitis , Enfermedad Aguda , Bases de Datos Factuales , Humanos , Pancreatitis/diagnóstico
4.
Expert Rev Gastroenterol Hepatol ; 14(12): 1159-1169, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32811202

RESUMEN

INTRODUCTION: The occurrence of perineal fistula is a significant evesnt in the evolution of Crohn's disease. Approximately 21% to 23% of patients develop perineal fistula at least once in their lifetime, approximately 30% of patients have cases of recurrence, and the refractory and recurrent perineal lesions of Crohn's disease impose a great economic burden on patients. The main purpose of this review was to investigate the quality of guidelines for perineal fistula in Crohn's disease. AREA COVERED: Relevant websites and databases were systematically searched to identify and select clinical guidelines related to perineal fistulas in Crohn's disease. Four independent reviewers assessed the eligible guidelines using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) and used intraclass correlation coefficients (ICC) to measure the agreement among the guideline reviewers. CONCLUSION: There is much room for improvement in the quality of guidelines for the management of perineal fistulas in Crohn's disease. The recommendations and evidence for guidelines for the management of perineal fistulas in Crohn's disease are quite heterogeneous, and guideline-developers would be well advised to address the above issues during future guideline development.


Asunto(s)
Enfermedad de Crohn , Fístula Rectal/terapia , Enfermedad de Crohn/complicaciones , Humanos , Guías de Práctica Clínica como Asunto , Fístula Rectal/etiología
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