Mikhail Panteleev

MSU, Faculty of physics

Systems Biology and Physiology Reports in 2021: a yearly report

Dear All,

I am happy to greet all readers, editors, reviewers, staff members and publishers of SBPR on the eve of year 2022. I thank all of you for your efforts in creating this journal and making it work despite all the challenges faced by a new independent journal in the age dominated by huge publishers, research societies and citation systems. Please accept my best wishes for the year 2022 in your professional and personal undertakings!

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Immune thrombocytopenia: what can the systems biology and systems physiology offer?

Immune thrombocytopenia (ITP) is an acquired bleeding disorder of autoimmune pathophysiology. The causes of ITP could be related to other pathology (viral, bacterial, or systemic), or ITP could develop without any apparent reason. While the immune system dysregulation mechanisms in ITP were described, its etiology remains unclear. Moreover, all existing treatment approaches are not specific for ITP, and its action is highly patient- specific. Here we describe recent findings in the origins and development of ITP and discuss novel experimental and theoretical approaches to diagnosing ITP and predicting therapy effects.

Schematic of immune thrombocytopenia mechanisms. The thrombocytopenia in patients could be caused by both T-cells cytotoxicity (CTLs are more active because T-regulatory cells and T-helpers provide dysregulated stimuli) and B-cells antibody production (plasma cells are producing antiplatelet antibodies of IgG and IgM classes; B-regulatory cells provide more activating signals to B-cells to produce antibodies). CTLs specifically attack platelets and induce their apoptosis. Antibodies from plasma cells opsonize platelets. Consecutively, opsonized platelets are eliminated through the spleen. CTLs – cytotoxic T-lymphocytes; Treg – T-regulatory cell; Th – T-helper; Breg – B-regulatory cell; BAFF – B-cell activating factor.
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#autoimmunity#ITP#platelets#acute/chronic ITP#computational modeling#murine models

Platelet functional responses and signalling: the molecular relationship. Part 2: receptors.

Small, non-nuclear cells, platelets, are primarily designed to form aggregates when blood vessels are damaged, stopping bleeding. To perform this function, platelets can implement several functional responses induced by various agonists and coordinated by a complex network of intracellular signaling triggered by a dozen of different receptors. This review, the second in a series, describes the known intracellular signaling pathways induced by platelet receptors in response to canonical and rare agonists. Particular focus will be on interaction points and “synergy” of platelet activation pathways and intermediate or “secondary” activation mediators that transmit a signal to functional manifestations.

Different degrees of the platelet activation in hemostasis. Upon weak stimulation, platelets pass into a weakly activated state, in which there is no clustering of platelet integrins and no significant change in the shape of platelets. This weak activation is reversible, and it corresponds to the state of platelets in the outer layers ("coat") of the thrombus. Upon stronger activation, platelet shape significantly changes. Platelets become irreversibly activated and aggregate. The secretion of platelet granules also occurs. At the maximum degree of activation, platelet mitochondria collapse, and platelets pass into a procoagulant state, exposing phosphatidylserine, which significantly accelerates blood plasma coagulation.
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#platelets#intracellular signaling#physiology

A strong correlation exists between platelet consumption and platelet hyperactivation in COVID-19 patients. Pilot study of the patient cohort from CCH RAS Hospital (Troitsk).

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It is known that in COVID-19, hypercoagulation and sometimes thrombocytopenia are related to disease severity. There is also controversial data on platelet participation in COVID-19 pathology. We aimed to determine the degree of platelet hyperactivation in COVID-19 patients. Whole blood flow cytometry with Annexin-V and lactadherin staining ("PS+ platelets") was utilized. Additionally, a stochastic mathematical model of platelet production and consumption was developed. Here we demonstrated that the percentage of PS+ platelets in COVID-19 patients was twofold that of healthy donors. There was a significant correlation between the amount of PS+ platelets and the percentage of lung damage in patients. No connection was found between platelet senescence and hospital therapy or patients' chronic diseases, except for chronic lung disease. Although no thrombocytopenia was observed in patients, the observed increase in platelet size (FSC-A parameter in flow cytometry) could indicate that platelet age is decreased in patients. The developed computational model of platelet turnover confirms the possibility of intense platelet consumption without noticeable changes in platelet count. We conclude that the observed platelet hyperactivation in COVID-19 could be caused by platelet activation in circulation, leading to platelet consumption without significant thrombocytopenia.

Computational model of platelet production in the presence of COVID-19 induced thrombosis. A – Detailed scheme of the model (most sensitive reactions are highlighted in red). B – Dependence of the average platelet count (green curve and dots) and platelet size (red curve and dots) from the platelet consumption index in the model. Platelet number and size in the absence of consumption lie in the areas, highlighted by green and red rectangles correspondingly. C – Platelet size distribution in the absence (green bars) and the presence (red bars) of consumption (with consumption index set to 2). Whiskers on all plots represent SD.
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Platelet functional responses and signalling: the molecular relationship. Part 1: responses.

Blood platelets are small anucleated cells whose main function is to form a plug upon vascular damage to stop bleeding. This role involves a number of functional responses induced by different agonists and coordinated by an intricate network of signal transduction pathways. Understanding this network is vital from both basic research point of view and for the purposes of drug target identification in thrombosis and hemostasis. This review series will focus on the regulation of platelet signalling, on tracking the molecular relationship between receptor activation and functional responses, and on the networking aspects of these pathways. The present paper, first one out of two, focuses on the description of platelet functional responses and of the conditions for their triggering.
Platelet functional responses within arterial thrombus.
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#hemostasis#platelet activation#platelet intracellular signaling#thrombosis#thrombus formation

Systems approaches meet biology and physiology: why do we need yet another journal?

Modern biological science in the past 50 years has made a spectacular journey providing us fascinating insights into the nature of living organisms and leading to accumulation of incredible amount of information. Nowadays, we observe introduction of the new systems approaches that allow us to supplement the qualitative nature of the life sciences by quantitative and mechanism-driven analysis. More and more scientists are becoming attracted by the unique opportunities that are provided by the novel synthetic approaches, encompassed by the systems biology, systems physiology and systems pharmacology in various fields. Right now, it is not simply mathematical or computational modelling of biological systems: a wide range of tools, including various approaches from big data field, progressive statistical methods, "omics" and others, are used to get insight into the mechanism of health and disease.
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