The role of phosphatidylserine on the membrane in immunity and blood coagulation

The negatively charged aminophospholipid, phosphatidylserine (PtdSer), is located in the inner leaflet of the plasma membrane in normal cells, and may be exposed to the outer leaflet under some immune and blood coagulation processes. Meanwhile, Ptdser exposed to apoptotic cells can be recognized and eliminated by various immune cells, whereas on the surface of activated platelets Ptdser interacts with coagulation factors prompting enhanced production of thrombin which significantly facilitates blood coagulation. In the case where PtdSer fails in exposure or mistakenly occurs, there are occurrences of certain immunological and haematological diseases, such as the Scott syndrome and Systemic lupus erythematosus. Besides, viruses (e.g., Human Immunodeficiency Virus (HIV), Ebola virus (EBOV)) can invade host cells through binding the exposed PtdSer. Most recently, the Corona Virus Disease 2019 (COVID-19) has been similarly linked to PtdSer or its receptors. Therefore, it is essential to comprehensively understand PtdSer and its functional characteristics. Therefore, this review summarizes Ptdser, its eversion mechanism; interaction mechanism, particularly with its immune receptors and coagulation factors; recognition sites; and its function in immune and blood processes. This review illustrates the potential aspects for the underlying pathogenic mechanism of PtdSer-related diseases, and the discovery of new therapeutic strategies as well.

Differential proteomic analysis demonstrates follicle fluid participate immune reaction and protein translation in yak

Background Ovarian follicle fluid (FF) as a microenvironment surrounding oocyte plays critical roles in physio-biochemical processes of follicle development and oocyte maturation. It is hypothesized that proteins in yak FF participate in the physio-biochemical pathways. The primary aims of this study were to find differentially expressed proteins (DEPs) between mature and immature FF, and to elucidating functions of the mature and immature FF in yak. Results The mature and immature FF samples were obtained from three healthy yaks that were nonpregnant, aged from four to five years, and free from any anatomical reproductive disorders. The FF samples were subjected to mass spectrometry with the isobaric tags for relative and absolute quantification (iTRAQ). The FF samples went through correlation analysis, principle component analysis, and expression pattern analysis based on quantification of the identified proteins. Four hundred sixty-three DEPs between mature and immature FF were identified. The DEPs between the mature and immature FF samples underwent gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), and protein-protein interaction (PPI) analysis. The DEPs highly expressed in the mature FF mainly took parts in the complement and coagulation cascades, defense response, acute-phase response, response to other organism pathways to avoid invasion of exogenous microorganisms. The complement activation pathway contains eight DEPs, namely C2, C5, C6, C7, C9, C4BPA, CFH, and MBL2. The three DEPs, CATHL4, CHGA, and PGLYRP1, take parts in defense response pathway to prevent invasion of exogenetic microorganism. The coagulation cascades pathway involves many coagulation factors, such as F7, F13A1, FGA, FGB, FGG, KLKB1, KNG1, MASP1, SERPINA1, and SERPIND1. While the DEPs highly expressed in the immature FF participated in protein translation, peptide biosynthetic process, DNA conformation change, and DNA geometric change pathways to facilitate follicle development. The translation pathway contains many ribosomal proteins, such as RPL3, RPL5, RPS3, RPS6, and other translation factors, such as EIF3J, EIF4G2, ETF1, MOV10, and NARS. The DNA conformation change and DNA geometric change involve nine DEPs, DDX1, G3BP1, HMGB1, HMGB2, HMGB3, MCM3, MCM5, MCM6, and RUVBL2. Furthermore, the expressed levels of the main DEPs, C2 and SERPIND1, were confirmed by western blot. Conclusions The differential proteomics revealed the up-regulated DEPs in mature FF take parts in immunoreaction to prevent invasion of microorganisms and the up-regulated DEPs in immature FF participate in protein synthesis, which may improve our knowledge of the follicular microenvironment and its biological roles for reproductive processes in yak. The DEPs, C2 and SERPIND1, can be considered as protein markers for mature yak follicle.

Prevalence of Anticoagulant Rodenticide Exposure in Red-tailed Hawks (Buteo jamaicensis) in New York State and Diagnostic Utility of Russell Viper Venom Test for Detecting Associated Coagulopathies

Anticoagulant rodenticides (ARs) continue to be used across the United States as a method for controlling unwanted rodent species. As a consequence, wild birds of prey are exposed to toxins by eating poisoned prey items. ARs prevent the hepatic recycling of vitamin K and thereby impede the post-translational processing of coagulation factors II, VII, IX, and X that is required for procoagulant complex assembly. Through this mechanism of action, ARs cause hemorrhage and death in their target species. Various studies have documented the persistence of these contaminants in birds of prey but few have attempted to use affordable and accessible diagnostic tests to diagnose exposure in free-ranging birds of prey. In our study free-ranging red-tailed hawks were found to be exposed to difethialone and brodifacoum. Eleven of sixteen (68%) livers tested for AR exposure were positive. Difethialone was found in 1/16 (6%) liver samples, and brodifacoum was detected in 15/16 (93%) liver samples. Difethialone was found at a concentration of 0.18 ppm and brodifacoum concentrations ranged from 0.003-0.234 ppm. Two out of 34 (6%) RTH assessed for blood rodenticide had brodifacoum in blood with measured concentrations of 0.003 and 0.006 ppm. The range of clotting times in the prothrombin time (PT) and Russell’s viper venom time assays for control RTH were 16.7 to 39.7 seconds and 11.5 to 91.8 seconds, respectively. No correlation was found between PT and RVVT in the control or free-range RTH, and there was no relationship found between the presence of liver anticoagulant residues and clotting times in the PT and RVVT.

Coagulation profile of human COVID-19 convalescent plasma

Convalescent plasma is used to treat COVID-19. There are theoretical concerns about the impact of pro-coagulant factors in convalescent plasma on the coagulation cascade particularly among patients with severe COVID-19. The aim of this study was to evaluate the coagulation profile of COVID-19 convalescent plasma. Clotting times and coagulation factor assays were compared between fresh frozen plasma, COVID-19 convalescent plasma, and pathogen-reduced COVID-19 convalescent plasma. Measurements included prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen, D-dimer, von Willebrand factor activity, von Willebrand factor antigen, coagulation factors II, V, VII–XII, protein S activity, protein C antigen, and alpha-2 plasmin inhibitor. Clotting times and coagulation factor assays were not different between COVID-19 convalescent plasma and fresh frozen plasma, except for protein C antigen. When compared to fresh frozen plasma and regular convalescent plasma, pathogen reduction treatment increased activated partial thromboplastin time and thrombin time, while reducing fibrinogen, coagulation factor II, V, VIII, IX, X, XI, XII, protein S activity, and alpha-2 plasmin inhibitor. The coagulation profiles of human COVID-19 convalescent plasma and standard fresh frozen plasma are not different. Pathogen reduced COVID-19 convalescent plasma is associated with reduction of coagulation factors and a slight prolongation of coagulation times, as anticipated. A key limitation of the study is that the COVID-19 disease course of the convalesced donors was not characterized.

The probable role and therapeutic potential of the PI3K/AKT signaling pathway in SARS-CoV-2 induced coagulopathy

Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is associated with a high mortality rate. The majority of deaths in this disease are caused by ARDS (acute respiratory distress syndrome) followed by cytokine storm and coagulation complications. Although alterations in the level of the number of coagulation factors have been detected in samples from COVID-19 patients, the direct molecular mechanism which has been involved in this pathologic process has not been explored yet. The PI3K/AKT signaling pathway is an intracellular pathway which plays a central role in cell survival. Also, in recent years the association between this pathway and coagulopathies has been well clarified. Therefore, based on the evidence on over-activity of the PI3K/AKT signaling pathway in SARS-CoV-2 infection, in the current review, the probable role of this cellular pathway as a therapeutic target for the prevention of coagulation complications in patients with COVID-19 is discussed.

Evaluation of the Effect of COVID-19 Pneumonia on Kidney Function

Background: Severe acute respiratory tract infection, pneumonia, kidney failure, and multi-organ failure may develop in cases that result in death due to COVID-19. It is emphasized that the awareness of healthcare professionals about kidney functions should be increased in cases of COVID-19 pneumonia. Quick and effective steps can be taken in the treatment of COVID-19 pneumonia with the controlling approach of nurses to changes in kidney functions. Method: This study was carried out retrospectively to evaluate the kidney functions of patients diagnosed with COVID-19 pneumonia who were hospitalized in the pandemic hospital. Hospital and nurse observation files of 120 patients who were introduced to COVID-19 pneumonia between 1 May and 30 November 2020 were examined. Categorical data were described as continuous data as median with interquartile range (IQR) and percentages (%). Results: In total, 30 patients (25.0%) required mechanical ventilation, Overall, 39.1% (47) developed acute kidney injury during hospitalization, out of which 10.8% reached stage 1, 15.0% reached stage 2, and 13.3% reached stage 3. Dialytic support was required for seven (17.1% of all patients). COVID-19 pneumonia patients had higher levels of aspartate aminotransferase (AST) (55.02±58.04), alanine aminotransferase (ALT) (74.07±140.94), lactate dehydrogenase (LDH) (483.48±477.51), C-reactive protein (CRP) (88.02±72.17), D-dimer (1023±1548.01), procalcitonin (3.70± 6.52). In addition, a proportion of COVID-19 pneumonia patients but no non-COVID-19 pneumonia patients had abnormally increased AST (10.0-274.0), ALT (7.0-854.0), LDH (164-3547), CRP (5.10- 310.90), D-dimer (151-6212), procalcitonin (195-433). SpO2 of COVID-19 pneumonia patients had 78-97%, patients who need dialysis treatment due to pneumonia, follow-up coagulation profile (Procalcitonin, LDH, D-dimer), liver-renal function (ALT, AST, Creatine, Urea, Albumin), assessing signs of DVT and psychological support. 89 patients (74.2%) received corticosteroid, 73 patients (60.8%) received expectorant, 61 patients (50.8%) received vitamin C or B complex, 110 patients (91.7%) received anticoagulant and 73 patients (60.8%) received antibiotics. All of the COVID-19 pneumonia patients received the antiviral drug. Conclusion: As the disease progresses, differences in laboratory results and radiological findings may indicate that some complications have developed. COVID-19 pneumonia draws attention with liver function tests such as AST / ALT, LDH, infection markers in the blood, and the high rate of coagulation factors such as PCT and D-dimer during the hospital stay. The fact that these elevated values ​​may cause necrosis in the kidneys also brings about the truth. Careful monitoring of laboratory findings such as elevation of AST / ALT, LDH, PCT, and D-dimer in patients who develop pneumonia due to COVID-19 may provide early action for kidney damage.

Coagulopathy due to vitamin k-dependent coagulation factors deficit as a unusual presentation of celiac disease

Resumen El gluten es una proteína presente principalmente en el trigo, cebada y centeno, que se utiliza ampliamente en el procesamiento de varios alimentos. Su ingesta se ha asociado con una variedad de trastornos clínicos de relevancia epidemiológica, denominados en conjunto trastornos relacionados con el gluten. De ellos, la enfermedad celíaca es la más importante por su implicancia clínica. La enfermedad celíaca se reconoce fundamentalmente por su clínica digestiva; sin embargo, su espectro de presentación puede ser muy amplio. Se presenta el caso de un paciente con antecedente de episodios hemorrágicos sin causa aparente, que concluyó en el diagnóstico de Enfermedad Celíaca, al presentar posteriormente clínica digestiva. Este caso enfatiza la necesidad de tener en consideración el diagnóstico de celiaquía ante un paciente con coagulopatía de origen desconocido, que permita instaurar de forma oportuna el tratamiento adecuado para evitar complicaciones.

Psychosocial risk factors in cardiac practice

<p>Cardiovascular diseases (CVD) remain the leading cause of death in Russia. Apart from conventional modified risk factors, population health, including CVD progression and related death, is influenced by psychosocial risk factors (PS RF). In theory, the role of PS RF can be explained by the significant changes in death rates within the Russian population during social and economic alterations. However, the significance of primary CVD RF has remained unchanged since the Soviet times. Nonetheless, PS RF does not receive much attention in our country. Thus, the current review aimed to introduce specialists focusing primarily on PS RF, such as low socioeconomic status, social isolation and low levels of social support, depressive disorders and personality traits (hostility and type D personality), which are now undoubtedly closely associated with unfavourable prognosis in patients with CVD. This summary also discusses the main pathophysiological mechanisms that may facilitate the progression of CVD, which include the activation of the hypothalamic–pituitary–adrenal axis, sympathoadrenal system with increased cardiovascular reactivity, endothelial function, inflammatory markers, platelets, coagulation factors, fibrinogen and lifestyle-associated factors. Thus, PS RF have considerable practical significance, not only for individual risk estimation but also in primary and secondary interventions for the prevention of CVD.</p><p>Received 4 May 2021. Revised 6 June 2021. Accepted 11 June 2021.</p><p><strong>Funding:</strong> The study did not have sponsorship.</p><p><strong>Conflict of interest: </strong>Authors declare no conflict of interest.</p><p><strong>Contribution of the authors: </strong>The authors contributed equally to this article.</p>

Cerebrovascular Accident Complicating Diabetic Ketoacidosis in a Nigerian Adolescent: A Case Report and Review of the Literature

Cerebrovascular accident (CVA) is a rare neurological complication of diabetic ketoacidosis (DKA) in the paediatric population. The risk of developing CVA in DKA patients is often increased due to abnormalities in coagulation factors, platelet activation, blood volume and flow, and vascular reactivity. Cerebral oedema, the most common neurological complication of DKA, may also predispose to CVA. We report the case of a -12-year-old adolescent with DKA complicated by CVA. She developed features of right hemispheric CVA while on admission and had radiological confirmation of an ischaemic CVA. This report highlights that cerebrovascular accidents in DKA can easily be missed or confused with cerebral oedema.

Russian recombinant coagulation factors: the technological background and the results of clinical studies

The prolongation of survival and the improvement of quality of life in patients with hemophilia A and B are only possible if hemostatic disorders caused by coagulation factor VIII and IX deficiency are managed effectively. Recombinant coagulation factors are playing an ever-increasing role in the preventive care of affected patients. The development, production and use of domestic recombinant coagulation factors opened up new treatment opportunities and improved access to preventive care for hemophilia patients. The results of clinical studies on the efficacy and safety of the Russian recombinant factors showed that they had similar efficacy and safety compared to the plasma derived clotting factors.