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Anuclear blood cells, platelets, are the basis for the formation of blood clots in human vessels. While antiplatelet therapy is most often used after ischemic events, there is a need for its personalization due to the limited effectiveness and risks of bleeding. Previously, we developed a series of computational models to describe intracellular platelet signaling and a set of experimental methods to characterize the platelets of a given patient. To build a personalized model of platelet signaling, we also conducted research on platelet proteomics. The aim of this study was to personalize the central module of intracellular platelet signaling responsible for the formation of calcium oscillations in response to activation. The model consists of 26 ordinary differential equations. To personalize the model, proteomics data were used and unknown model parameters were selected based on experimental data on the shape and frequency of calcium oscillations in single platelets. As a result of the study, it has been shown that the key personalized parameters of the platelet oscillatory response are the degree of asymmetry of a single calcium spike and the maximum frequency of oscillations. Based on the listed experimentally determined parameters and proteomics data, an algorithm for personalization of the model has been proposed. Here we considered three healthy pediatric donors of different ages. Based on the models, personal curves of platelet calcium response to activation were obtained. The analysis of the models has shown that while there is a large heterogeneity of individual indicators of intracellular signaling, such as the activity of calcium pumps (SERCA) and inositoltriphosphate (IP₃) receptors (IP₃R), these indicators compensate each other in each donors. This observation is confirmed by the analysis of proteomics data from 15 healthy patients: this analysis demonstrates a correlation between the total amount of SERCA and IP₃R. Thus, several new features of human platelet calcium signaling are shown and an algorithm for personalizing its model is proposed.
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http://dx.doi.org/10.18097/PBMC20247006394 | DOI Listing |
Biomed Khim
December 2024
Center for Theoretical Problems of Physico-Chemical Pharmacology, Russian Academy of Sciences, Moscow, Russia; Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
Anuclear blood cells, platelets, are the basis for the formation of blood clots in human vessels. While antiplatelet therapy is most often used after ischemic events, there is a need for its personalization due to the limited effectiveness and risks of bleeding. Previously, we developed a series of computational models to describe intracellular platelet signaling and a set of experimental methods to characterize the platelets of a given patient.
View Article and Find Full Text PDFZhonghua Wei Zhong Bing Ji Jiu Yi Xue
November 2024
Department of Intensive Care Medicine, the First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu, China. Corresponding author: Wang Jun, Email:
Objective: To develop and validate a predictive model of 28-day mortality in sepsis based on lactate dehydrogenase-to-albumin ratio (LAR).
Methods: Sepsis patients diagnosed in the department of intensive care medicine of the First Affiliated Hospital of Soochow University from August 1, 2017 to September 1, 2022 were retrospective selected. Clinical data, laboratory indicators, disease severity scores [acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA)] were collected.
PLoS One
December 2024
The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Colitis is a complex multifactorial disease with an unknown aetiology that mainly manifests as chronic refractory colon transmission disorders. Smooth muscle, the main source of colon transmission power, consists of not only smooth muscle cells (SMCs) but also PDGFRα+ cells that mediate smooth muscle relaxation and ICCs that mediate contraction. PDGFRα+ cells and their unique small conductance Ca2+-activated K (SK3) channels are crucial in regulating colonic transit by exerting inhibitory effects.
View Article and Find Full Text PDFAnn Hematol
December 2024
Department of Gastroenterology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, No. 1678 Dongfang Road, Shanghai, China.
We aimed to investigate whether early clinical indicators were associated with eventual disease severity, and to develop a predictive model for severe asparaginase-associated pancreatitis (AAP). Seventy-five acute lymphoblastic leukaemia (ALL) cases with AAP admitted to Shanghai Children's Medical Center from March 2013 to August 2023 were divided into non-severe (n = 44) and severe (n = 31) groups based on Atlanta diagnostic and AAP grading criteria. We compared essential information, asparaginase(ASP) dosage form, cumulative dose, clinical characteristics and laboratory tests between the groups.
View Article and Find Full Text PDFTransfus Med Hemother
December 2024
Department of Nephrology, Xiangya Hospital, Central South University, Changsha, China.
Introduction: Protein A immunoadsorption (IA) is proving to be an effective treatment method for autoimmune diseases and other disorders. Regional citrate anticoagulation (RCA) prevents clotting in extracorporeal circuits without increasing hemorrhage risk in high bleeding risk patients, but there are no specific guidelines for its application in IA. We aimed to evaluate the safety and adverse effects of RCA used in IA therapy.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!