Loss of Bace1 in Mice Does Not Alter the Severity of Caerulein Induced Pancreatitis

Heindl, Mario; Tuennemann, Jan; Sommerer, Ines; Mössner, Joachim; Hoffmeister, Albrecht

doi:10.1371/journal.pone.0125556

Cited by 4 publications

(4 citation statements)

References 31 publications

(19 reference statements)

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“…After staining, they were evaluated using a Leica DM6 microscope (Leica Microsystems SpA, Milan, Italy) with Leica LAS X Navigator software (Leica Microsystems SpA). The injury score for both pancreas and lung was calculated as previously described [ 40 , 42 ].…”

Section: Methodsmentioning

confidence: 99%

Cashew (Anacardium occidentale L.) Nuts Modulate the Nrf2 and NLRP3 Pathways in Pancreas and Lung after Induction of Acute Pancreatitis by Cerulein

et al. 2020

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Background: One of the most common co-morbidities, that often leads to death, associated with acute pancreatitis (AP) is represented by acute lung injury (ALI). While many aspects of AP-induced lung inflammation have been investigated, the involvement of specific pathways, such as those centered on nuclear factor E2-related factor 2 (Nrf2) and nucleotide-binding domain leucine-rich repeat (NLR) and pyrin domain containing receptor 3 (NLRP3), has not been fully elucidated. Methods: To investigate the effect of cashew (Anacardium occidentale L.) nuts on pancreatic and lung injury induced by cerulein injection, cerulein (50 μg/kg) was administered to CD1 mice for 10 h. Oral treatment with cashew nuts at a dose of 100 mg/kg was given 30 min and 2 h after the first cerulein injection. One hour after the final cerulein injection, mice were euthanized and blood, lung and pancreatic tissue samples were collected. Results: Cashew nuts were able to (1) reduce histological damage; (2) mitigate the induction of mast cell degranulation as well as the activity of myeloperoxidase and malondialdehyde; (3) decrease the activity levels of amylase and lipase as well as the levels of pro-inflammatory cytokines; and (4) enhance the activation of the Nrf2 pathway and suppress the activation of the NLRP3 pathway in response to cerulein in both pancreas and lung. Conclusions: Cashew nuts could have a beneficial effect not only on pancreatitis but also on lung injury induced by cerulein.

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Section: Methodsmentioning

confidence: 99%

Cashew (Anacardium occidentale L.) Nuts Modulate the Nrf2 and NLRP3 Pathways in Pancreas and Lung after Induction of Acute Pancreatitis by Cerulein

et al. 2020

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“…Sections were stained with hematoxylin and eosin (HE) using a full-automatic microscope slide appliance (Shandon Varistain 24–4, Thermo Shandon Ltd.) as described [30]. Immunohistochemistry was performed as previously described [31]. A polyclonal rabbit antibody against myeloperoxidase was purchased from Abcam (Cambridge, UK) and used in a dilution of 1:100 in 2% donkey serum (SIGMA, St. Louis, USA).…”

Section: Methodsmentioning

confidence: 99%

Azithromycin does not improve disease severity in acute experimental pancreatitis

et al. 2019

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Acute pancreatitis is a severe systemic disease triggered by a sterile inflammation and initial local tissue damage of the pancreas. Immune cells infiltrating into the pancreas are main mediators of acute pancreatitis pathogenesis. In addition to their antimicrobial potency, macrolides possess anti-inflammatory and immunomodulatory properties which are routinely used in patients with chronic airway infections and might also beneficial in the treatment of acute lung injury. We here tested the hypothesis that the macrolide antibiotic azithromycin can improve the course of acute experimental pancreatitis via ameliorating the damage imposed by sterile inflammation, and could be used as a disease specific therapy. However, our data show that azithromycin does not have influence on caerulein induced acute pancreatitis in terms of reduction of organ damage, and disease severity. Furthermore Infiltration of immune cells into the pancreas or the lungs was not attenuated by azithromycin as compared to controls or ampicillin treated animals with acute experimental pancreatitis. We conclude that in the chosen model, azithromycin does not have any beneficial effects and that its immunomodulatory properties cannot be used to decrease disease severity in the model of caerulein-induced pancreatitis in mice.

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“…according to an extensive literature-based research [26][27][28][29][30][31][32][33][34][35][36][37][38][39].…”

Section: In Silico Stroke Modeling Repositioning and Identification O...mentioning

confidence: 99%

Ceruletide and Alpha-1 Antitrypsin as a Novel Combination Therapy for Ischemic Stroke

et al. 2022

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Ischemic stroke is a primary cause of morbidity and mortality worldwide. Beyond the approved thrombolytic therapies, there is no effective treatment to mitigate its progression. Drug repositioning combinational therapies are becoming promising approaches to identify new uses of existing drugs to synergically target multiple disease-response mechanisms underlying complex pathologies. Here, we used a systems biology-based approach based on artificial intelligence and pattern recognition tools to generate in silico mathematical models mimicking the ischemic stroke pathology. Combinational treatments were acquired by screening these models with more than 5 million two-by-two combinations of drugs. A drug combination (CA) formed by ceruletide and alpha-1 antitrypsin showing a predicted value of neuroprotection of 92% was evaluated for their synergic neuroprotective effects in a mouse pre-clinical stroke model. The administration of both drugs in combination was safe and effective in reducing by 39.42% the infarct volume 24 h after cerebral ischemia. This neuroprotection was not observed when drugs were given individually. Importantly, potential incompatibilities of the drug combination with tPA thrombolysis were discarded in vitro and in vivo by using a mouse thromboembolic stroke model with t-PA-induced reperfusion, revealing an improvement in the forepaw strength 72 h after stroke in CA-treated mice. Finally, we identified the predicted mechanisms of action of ceruletide and alpha-1 antitrypsin and we demonstrated that CA modulates EGFR and ANGPT-1 levels in circulation within the acute phase after stroke. In conclusion, we have identified a promising combinational treatment with neuroprotective effects for the treatment of ischemic stroke.

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Loss of Bace1 in Mice Does Not Alter the Severity of Caerulein Induced Pancreatitis

Cited by 4 publications

References 31 publications

Cashew (Anacardium occidentale L.) Nuts Modulate the Nrf2 and NLRP3 Pathways in Pancreas and Lung after Induction of Acute Pancreatitis by Cerulein

Cashew (Anacardium occidentale L.) Nuts Modulate the Nrf2 and NLRP3 Pathways in Pancreas and Lung after Induction of Acute Pancreatitis by Cerulein

Azithromycin does not improve disease severity in acute experimental pancreatitis

Ceruletide and Alpha-1 Antitrypsin as a Novel Combination Therapy for Ischemic Stroke

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