SARS-CoV-2 S Protein Subunit 1 Elicits Ca2+ Influx – Dependent Ca2+ Signals in Pancreatic Stellate Cells and Macrophages In Situ

Function, Journal Year: 2022, Volume and Issue: 3(2)

Published: Jan. 1, 2022

The S protein subunit 1 (S1) of SARS-CoV-2 is known to be responsible for the binding virus host cell receptors, but initial intracellular signalling steps following receptor activation cells in exocrine pancreas are unknown. Using an intact live mouse pancreatic lobule preparation, we observed that S1 elicited Ca

Language: Английский

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Early prediction of acute necrotizing pancreatitis by artificial intelligence: a prospective cohort-analysis of 2387 cases

Scientific Reports, Journal Year: 2022, Volume and Issue: 12(1)

Published: May 12, 2022

Abstract Pancreatic necrosis is a consistent prognostic factor in acute pancreatitis (AP). However, the clinical scores currently use are either too complicated or require data that unavailable on admission lack sufficient predictive value. We therefore aimed to develop tool aid prediction. The XGBoost machine learning algorithm processed from 2387 patients with AP. confidence of model was estimated by bootstrapping method and interpreted via 10th 90th percentiles prediction scores. Shapley Additive exPlanations (SHAP) values were calculated quantify contribution each variable provided. Finally, implemented as an online application using Streamlit Python-based framework. classifier provided AUC value 0.757. Glucose, C-reactive protein, alkaline phosphatase, gender total white blood cell count have most impact based SHAP values. relationship between size training dataset performance shows can be improved. This study combines artificial intelligence. potential this comparable current scoring systems has several advantages over them.

Language: Английский

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Autophagy, Acute Pancreatitis and the Metamorphoses of a Trypsinogen-Activating Organelle

Cells, Journal Year: 2022, Volume and Issue: 11(16), P. 2514 - 2514

Published: Aug. 12, 2022

Recent studies have highlighted the importance of autophagy and particularly non-canonical in development progression acute pancreatitis (a frequent disease with considerable morbidity significant mortality). An important early event is intrapancreatic activation trypsinogen, (i.e., formation trypsin) leading to autodigestion organ. Another prominent phenomenon associated initiation this vacuolisation specifically giant endocytic vacuoles pancreatic acinar cells. These organelles develop cells exposed several inducers (including taurolithocholic acid high concentrations secretagogues cholecystokinin acetylcholine). Notably, trypsinogen occurs vacuoles. trypsinogen-activating undergo activation, long-distance trafficking, autophagy. In review, we will discuss role focus on recently discovered LAP-like (LNCA)

Language: Английский

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Ca²⁺ signals in pancreatic acinar cells in response to physiological stimulation in vivo

The Journal of Physiology, Journal Year: 2023, Volume and Issue: 601(12), P. 2391 - 2405

Published: March 25, 2023

Abstract The exocrine pancreas secretes fluid and digestive enzymes in response to parasympathetic release of acetylcholine (ACh) via the vagus nerve gut hormone cholecystokinin (CCK). Both secretion exocytosis secretory granules containing zymogens are dependent on an increase cytosolic [Ca 2+ ] acinar cells. It is thought that specific spatiotemporal characteristics Ca signals fundamental for appropriate these properties disrupted disease states pancreas. While extensive research has been performed characterize signalling cells, this exclusively achieved ex vivo preparations where it difficult mimic physiological conditions. Here we have developed a method optically observe pancreatic using genetically expressed indicator imaged with multi‐photon microscopy live animals. In , cells exhibited baseline activity fasted animals, which was CCK1 receptors (CCK1Rs). stimulation intrinsic nervous input administration systemic CCK induced oscillatory proportion but maximum frequencies were vastly different. Upon feeding, also observed, CCK1Rs. No evidence vago‐vagal reflex mediating effects observed. Our revealed spatial temporal profile physiologically evoked signals, will provide new insights into future studies mechanisms underlying physiology pathological image Key points pancreas, fundamentally important by neurotransmitter cholecystokinin. These previously defined studies. report mouse engineered express Specific ‘signatures’ probably stimulating neural administration. result direct action ACh not indirectly through reflex.

Language: Английский

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The role of Ca2+ signalling in the pathology of exocrine pancreas

Cell Calcium, Journal Year: 2023, Volume and Issue: 112, P. 102740 - 102740

Published: April 8, 2023

Exocrine pancreas has been the field of many successful studies in pancreatic physiology and pathology. However, related disease - acute pancreatitis (AP) is still takes it toll with more than 100,000 deaths worldwide per year. In spite significant scientific progress several human trials currently running for AP, there no specific treatment clinic. Studies mechanism initiation AP have identified two crucial conditions: sustained elevations cytoplasmic calcium concentration (Ca2+ plateau) significantly reduced intracellular energy (ATP depletion). These hallmarks are interdependent, i.e., Ca2+ plateau increase demand its clearance while production greatly affected by Result long standing destabilisation secretory granules premature activation digestive enzymes leading to necrotic cell death. Main attempts so far break vicious circle death concentrated on reduction overload or ATP depletion. This review will summarise these approaches, including recent developments potential therapies AP.

Language: Английский

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