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The maintenance of homeostasis of the intestinal epithelium depends on the complex process of epithelial cells differentiation, which repeatedly continues throughout the entire life. Many studies suggest, that cellular differentiation is regulated by glycosylation, or at least that changes of the latter are the hallmark of the process. The detailed description and understanding of this relationship are important in the context of gastrointestinal tract disease, including cancer. Here we employ a broadly used in vitro model of intestinal cell differentiation to track the glycosylation changes in details. We analyzed the glycoproteome- and glycosecretome-derived N-glycomes of undifferentiated Caco-2 adenocarcinoma cells and Caco-2-derived enterocyte-like cells. We used HILIC-HPLC and MALDI-ToF-MS approach together with exoglycosidases digestions to describe qualitative and quantitative N-glycosylation changes upon differentiation. Derived glycan traits analysis revealed, that differentiation results in substantial upregulation of sialylation of glycoproteome and increment of fucosylation within glycosecretome. This was also clearly visible when we analyzed the abundances of individual glycan species. Moreover, we observed the characteristic shift within oligomannose N-glycans, suggesting the augmentation of mannose trimming, resulting in downregulation of H8N2 and upregulation of H5N2 glycan. This was supported by elevated expression of Golgi alpha-mannosidases (especially MAN1C1). We hypothesize, that intensified mannose trimming at the initial steps of N-glycosylation pathway during differentiation, together with the remodeling of the expression of key glycosyltransferases leads to increased diversity of N-glycans and enhanced fucosylation and sialylation of complex structures. Finally, we propose H4N5F1 glycan as a potential biomarker of intestinal epithelial cell differentiation., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose: We aimed to evaluate the effects of unilateral vagotomy (right-VR or left-VL) on the severity of caerulein-induced acute pancreatitis (AP)., Material and Methods: VR or VL was done in Wistar rats 4 days before AP, except in control, sham operated group. Following 5 h administration of subcutaneous injections of caerulein, the pancreatic blood flow (PBF), serum lipase and IL-10 in caval blood samples were measured. The pancreatic specimens were taken from sacrificed rats for the assessment of MDA-4-HNE and morphology., Results: PBF decreased from 310 ± 20 ml/min/100 g of tissue in control rats to 130 ± 12 units in AP (p < 0.01). VR and VL alleviated this effect to 234 ± 22 and 229 ± 26 units, respectively, (p < 0.01). There was an immense increase of serum lipase in AP, from 100 ± 7 U/L up to 5220 ± 210 U/L (p < 0.01). Only VL limited this increase to 3469 ± 300 U/L (p < 0.01). Serum IL-10 increased uniformly in AP, without any effect of preceding VR or VL. VL performed in rats subjected subsequently to AP resulted in stronger reduction of histological changes, such as pancreatic edema and leukocyte infiltration, than the above parameters in AP rats with VR. MDA+4-HNE increased from 7.5 ± 0.1 pmol/g of tissue in control group to 30.6 ± 3 units in AP group (p < 0.01). Concentration of MDA+4-HNE in pancreatic tissue achieved 16.48 ± 3 pmol/g after VR and 13.84 ± 4 pmol/g following VL., Conclusion: Our observation might suggest that protective effect of VL could be stronger than VR in the protection on AP. However changes of PBF seem to be similar in both groups of rats., (Copyright © 2019 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.)

Purpose: We assessed the effect of bilateral vagotomy (BV) on the course of acute caerulein-induced pancreatitis (AP) in the rat., Material/methods: The study was performed on Wistar rats surgically prepared by subdiaphragmatic BV. Control group underwent sham operation. Four days later, AP was induced by subcutaneous injection of caerulein (25 μg/kg/5h) to the conscious animals with or without BV. After administration of caerulein the blood samples were taken for determination of serum lipase activity and interleukin-10 (IL-10) concentration. Pancreatic tissue samples were subjected to histological examinations and to the measurement of lipid peroxidation products (MDA+4-HNE) concentration and the activity of an antioxidant enzyme - glutathione peroxidase (GPx). After application of caerulein pancreatic blood flow was measured by laser Doppler flowmetry., Results: AP was manifested by oedema and neutrophil infiltration of the pancreatic tissue and accompanied by significant increases of serum lipase activity, serum concentration of IL-10 and pancreatic concentration of MDA+4HNE (ca. 50×, 2× and 4× respectively p ≥ 0.05). Pancreatic activity of GPx and pancreatic blood flow were decreased (both by 60%). In vagotomised rats with AP serum lipase activity and pancreatic concentration of MDA+4-HNE were lower whereas Il-10 concentration and pancreatic activity of GPx, as well as pancreatic blood flow were significantly higher as compared to AP rats with intact vagal nerves. In AP rats with vagotomy all histological signs of pancreatitis were significantly reduced., Conclusions: Bilateral vagotomy resulted in the significant attenuation of caerulein-induced pancreatitis in the rat., (Copyright © 2014 Medical University of Bialystok. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.)

Unlabelled: Growth hormone (GH) has been shown to protect the intestinal barrier integrity and to stimulate the production of insulin-like growth factor 1 (IGF-1), which inhibits the development of acute pancreatitis. Sensory nerves are implicated in the protection of pancreatic tissue against acute inflammation. The aim of this study was to investigate the influence of exogenous GH on acute pancreatitis (AP) and to assess the involvement of sensory nerves and IGF-1 in above effect. Studies were performed on Wistar rats. AP was induced by subcutaneous administration of caerulein (25mug/kg) to the conscious animals. GH (1 or 2mg/kg) was administered to the rats as an intraperitoneal injection 30min prior to the start of AP. To deactivate sensory nerves capsaicin was given at total dose of 100mg/kg 10days before the experiments. AP was confirmed by histological examination and manifested by the significant rises of pancreatic weight, and serum activities of lipase, TNFalpha and IL-10 (by 550%, 300% and 50%, respectively), whereas IGF-1 blood concentration was markedly reduced. Administration of GH prior to the caerulein infusion significantly increased GH, IGF-1 and IL-10 blood levels, attenuated harmful effects of AP and reduced histological manifestations of pancreatitis in the rats with intact sensory nerves. This was accompanied by the reduction of serum lipase, and TNFalpha activities. In the AP rats with capsaicin-deactivated sensory nerves GH failed to protect the pancreas against acute damage and, as a consequence of above deactivation, IGF-1 was low., Conclusion: GH modulates the development of acute pancreatitis in the presence of active sensory nerves probably via stimulation of IGF-1 release.

The effects of administration of (pyro)Glu-His-Gly-OH and its analogs on food consumption and 2-Deoxy-D-Glucose (2-DG)-induced gastric acid secretion were examined in rats. (Pyro)Glu-His-Gly-OH and (pyro)Glu-His-EA significantly reduced food consumption, but not gastric acid secretion as compared with controls. The tripeptides: (pyro)Glu-3Me-His-Gly-OH, (pyro)Glu-His-D-Ala-OH, and (pyro)Glu-Phe-Gly-OH were found to significantly inhibit 2-DG-induced gastric acid secretion. Our results indicate that some analogs of (pyro)Glu-His-Gly-OH cause a greater inhibition of food consumption or gastric acid secretion in rats than the original tripeptide, in analogy to findings obtained in dogs.