The influence of erythropoietin on apoptosis and fibrosis in the early phase of chronic pancreatitis in rats

Kazmierak, Weronika; Korolczuk, Agnieszka; Kurzepa, Jacek; Czechowska, Grażyna; Boguszewska-Czubara, Anna; Mądro, Agnieszka

doi:10.5114/aoms.2020.99800

Cited by 3 publications

(1 citation statement)

References 54 publications

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“…A meta-analysis showed that nearly 70% of RAP patients did not progress to CP [ 4 ]. Identifying risk factors for progression of RAP to CP is important because it could facilitate earlier intervention and may potentially delay or avoid the onset of CP, although there were some drugs that might delay CP progression [ 5 ]. To evaluate the risk factors of patients with RAP progression to CP, we designed a retrospective study involving a cohort of 265 patients with RAP.…”

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confidence: 99%

Early identification of high-risk patients with acute recurrent pancreatitis progression to chronic pancreatitis

Chang

et al. 2022

Arch Med Sci

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IntroductionThe aim of the study was to develop a simple tool for early identification of high-risk patients with recurrent acute pancreatitis (RAP) progression to chronic pancreatitis (CP) in primary hospitals or outpatient clinics.Material and methodsThis retrospective cohort study included 265 patients with RAP.ResultsA nomogram for RAP progression to CP was developed and the C-index of the model was 0.817 (95% CI: 0.72–0.91). Patients were divided into two risk groups according to the nomogram prediction scores and a higher proportion of patients in the high-risk group progressed to CP.ConclusionsThe nomogram provided a means of predicting which patients were at high risk of progression to CP.

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confidence: 99%

Early identification of high-risk patients with acute recurrent pancreatitis progression to chronic pancreatitis

Chang

et al. 2022

Arch Med Sci

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Immortalized mesenchymal stromal cells overexpressing alpha‐1 antitrypsin protect acinar cells from apoptotic and ferroptotic cell death

Shoeibi,

Green,

Wei

et al. 2024

J Cellular Molecular Medi

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Chronic pancreatitis (CP) is a progressive inflammatory disorder that impairs endocrine and exocrine function. Our previous work showed that mesenchymal stem/stromal cells (MSCs) and MSCs overexpressing alpha‐1 antitrypsin (AAT‐MSCs) could be therapeutic tools for CP. However, primary MSCs are predisposed to undergo senescence during culture expansion, which limits their therapeutic applications. We generated and characterized immortalized human MSCs (iMSCs) and AAT‐MSCs (iAAT‐MSCs) and tested their protective effect on 2,4,6‐Trinitrobenzenesulfonic acid (TNBS)‐induced acinar cell death in an in vitro cell culture system. Primary MSCs were immortalized by transduction with simian virus 40 large T antigen (SV40LT), and the resulting iMSC and iAAT‐MSC lines were analysed for proliferation, senescence, phenotype and multi‐differentiation potential. Subsequently, apoptosis and ferroptosis pathways were investigated by assessing changes before and after TNBS treatment. Coculture of iMSCs and iAAT‐MSCs with acinar cell lines inhibited early cell death induced by TNBS, reduced ER stress and reversed TNBS‐induced protein reduction at tight junctions. Additionally, iMSCs and iAAT‐MSCs exerted such protection by regulating mitochondrial respiration, ATP content and ROS production in TNBS‐induced acinar cells. Furthermore, iMSCs and iAAT‐MSCs ameliorated TNBS‐induced ferroptosis by modulating iron generation and ROS production and regulating the ferritin heavy chain 1 (FTH1)/protein disulfide isomerase (PDI)/glutathione peroxide 4 (GPX4) signalling pathways in acinar cells. These findings identify ferroptosis as an unrecognized mechanism that leads to TNBS‐induced cell death and offer mechanistic insights relevant to using stem cell therapy to treat acinar cell death associated with CP.

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Immortalized Mesenchymal Stromal Cells Overexpressing Alpha-1 Antitrypsin Protect Acinar Cells from Apoptotic and Ferroptotic Cell Death

Shoeibi¹,

Green²,

Wang³

et al. 2023

Preprint

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Chronic pancreatitis (CP) is a progressive inflammatory disorder that impairs endocrine and exocrine function. Our previous work suggests that mesenchymal stem/stromal cells (MSCs) and MSCs overexpressing alpha-1 antitrypsin (AAT-MSCs) could be therapeutic tools for CP treatment in mouse models. However, primary MSCs have a predisposition to undergo senescence during culture expansion which limits their therapeutic applications. Here we generated and characterized immortalized human MSCs (iMSCs) and AAT-MSCs (iAAT-MSCs) and tested their protective effect on 2,4,6-Trinitrobenzenesulfonic acid (TNBS) -induced acinar cell death in an in vitro cell culture system. Primary MSCs were immortalized by transduction with simian virus 40 large T antigen (SV40LT), and the resulting iMSC and iAAT-MSC lines were analyzed for proliferation, senescence, phenotype, and multi-differentiation potential. Subsequently, the impact of these cells on TNBS-induced cell death was measured and compared. Both apoptosis and ferroptosis pathways were investigated by assessing changes of critical factors before and after cell treatment. Coculture of iMSCs and iAAT-MSCs with acinar cell lines inhibited early apoptosis induced by TNBS, reduced ER stress, and reversed TNBS-induced protein reduction at tight junctions. Additionally, iMSCs and iAAT-MSCs exerted such protection by regulating mitochondrial respiration, ATP content, and ROS production in TNBS-induced acinar cells. Furthermore, iMSCs and iAAT-MSCs ameliorated ferroptosis by regulating the ferritin heavy chain 1 (FTH1)/protein disulfide isomerase (PDI)/glutathione peroxide 4 (GPX4) signaling pathways and by modulating ROS function and iron generation in acinar cells. These findings identified ferroptosis as one of the mechanisms that leads to TNBS-induced cell death and offer mechanistic insights relevant to using stem cell therapy for the treatment of CP.

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The influence of erythropoietin on apoptosis and fibrosis in the early phase of chronic pancreatitis in rats

Cited by 3 publications

References 54 publications

Early identification of high-risk patients with acute recurrent pancreatitis progression to chronic pancreatitis

Early identification of high-risk patients with acute recurrent pancreatitis progression to chronic pancreatitis

Immortalized mesenchymal stromal cells overexpressing alpha‐1 antitrypsin protect acinar cells from apoptotic and ferroptotic cell death

Immortalized Mesenchymal Stromal Cells Overexpressing Alpha-1 Antitrypsin Protect Acinar Cells from Apoptotic and Ferroptotic Cell Death

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