Flavonol and A-type procyanidin-rich extracts of Prunus spinosa L. flower exhibit anticoagulant activity through direct thrombin inhibition, but do not affect platelet aggregation in vitro.

Background: Blackthorn flower (Prunus spinosa L.) is a traditional herbal remedy recommended for treating cardiovascular diseases (CVDs). Aim: This in vitro study investigates the effects of flavonol and A-type procyanidin-rich blackthorn flower extracts on the hemostatic system, including the blood plasma coagulation cascade and platelet aggregation. Methods: Six distinct extracts, characterized through various techniques, including LC-MS/MS, were assessed at in vivo-relevant levels (1-50 µg/mL) for their antithrombotic activity. The thrombin, prothrombin, and activated partial thromboplastin times were measured. Additionally, the thrombin enzymatic activity was tested using the chromogenic substrate S-2238 and fibrinogen as the physiological substrate of the enzyme. To gain insights into the mechanism of action, the interactions between the primary extracts' constituents, their potential metabolites, and thrombin were examined in silico. The computational analyses were complemented by in vitro experiments and circular dichroism spectroscopy. The platelet aggregation in human platelet-rich plasma was assessed after ADP or collagen stimulation. Furthermore, the extracts' biocompatibility was tested on human peripheral blood mononuclear cells (PBMCs) and red blood cells (RBCs). Results: The extracts slightly prolonged the prothrombin and thrombin times and effectively inhibited the thrombin's enzymatic activity, reducing its amidolytic and proteolytic functions at 50 µg/mL by 91.2% and 74.8%, respectively. In silico molecular docking demonstrated a strong binding affinity of the examined polyphenols and their metabolites to thrombin. Most analytes bound exclusively within the enzyme active site; however, afzelin, kaempferitrin, and procyanidin A2 revealed the affinity to additional binding sites, including exosite I. The structure-activity relationship of flavonols as thrombin inhibitors was studied in vitro. Circular dichroism spectroscopy confirmed that the interactions between thrombin and the compounds (even at 1 µg/mL) induce alterations within the α-helices' secondary structure, resulting in noticeable changes in the enzyme's CD spectrum. On the other hand, the extracts did not influence platelet aggregation. Eventually, their cellular biocompatibility with PBMCs and RBCs was confirmed. Conclusion: The extracts directly inhibit thrombin, a critical serine protease in hemostasis and a prime anticoagulant drug target, and do not exhibit antiplatelet effects. This study enhances the knowledge of the biological activity of blackthorn flowers and supports their traditional use in CVDs.

Social Researchers' Approaches to Research Ethics During the COVID-19 Pandemic: An Exploratory Study.

The global COVID-19 pandemic and quarantine/distancing measures have forced researchers to cope with a new situation. This paper aimed to analyze how the pandemic and its associated constraints have affected social researchers' approach to research ethics. Drawing on an online qualitative survey with 193 Polish social researchers conducted in April and May 2020, we distinguished three approaches: nothing has changed, opportunity-oriented, and precautionary. According to the first, the pandemic was not regarded as a situation that required additional reflection on ethical issues or changes in research approaches. By contrast, the other two were based on the assumption that the pandemic affected research project ethics. The difference was in the assessment of changes in the area of ethics. The pandemic presented an opportunity and a threat to the ethicality of research, respectively. We discuss the implications of all three approaches for research and education.

"There must be Someone's Name Under Every Bit of Text, Even if it is Unimportant or Incorrect": Plagiarism as a Learning Strategy.

The article offers analyses of the phenomenon of copying (plagiarism) in higher education. The analyses were based on a quantitative survey using questionnaires, conducted in 2019 at one of the Polish universities. Plagiarism is discussed here both as an element of the learning process and a subject of public practices. The article presents students' definitions of plagiarism, their strategies for unclear or difficult situations, their experiences with plagiarism and their opinions on how serious and widespread this phenomenon is. Focusing on the non-plagiarism norm, that is the rule that students are not allowed to plagiarize, and in order to redefine it we have determined two strategies adopted by students. The first is withdrawing in fear of making a mistake (omitting the norm), which means not using referencing in unclear situations, e.g. when the data about the source of information are absent. The second is reducing the scope of the norm applicability (limiting the norm), characterized by the fact that there are areas where the non-plagiarism norm must be observed more closely and those where it is not so important, e.g. respondents classify works as credit-level and diploma-level texts, as in the credit-level work they "can" sometimes plagiarize since the detection rate is poor and consequences are not severe. The presented results are particularly significant for interpreting plagiarism in an international context (no uniform definition of plagiarism) and for policies aimed at limiting the scale of the phenomenon (plagiarism detection systems1).

Increased endothelial thrombomodulin (TM) expression in pregnancies complicated by IUGR.

Thrombomodulin (TM) is a cell surface receptor playing an important role in endothelial cell anticoagulant activity. TM is also known as a factor of angiogenesis; low TM activity correlates with impaired angiogenesis. Since vascular lesions with disorders of the placental coagulation and inadequate angiogenesis can be associated with IUGR, we hypothesized that thrombomodulin expression in the villous vasculature and syncytiotrophoblast of placentae complicated by IUGR might differ from those of normal pregnancies. Representative tissue samples of normal, IUGR as well as 1st and 2nd trimester (n = 12) placentae were collected. Immunohistochemistry (APAAP) of paraffin tissue sections was performed using monoclonal antibodies specific for TM and PECAM. The percentage of immunopositive vessels and the intensity of immunoreactivity was assessed. Vascular endothelium and syncytiotrophoblast stained positive for TM. Immunoreactivity for TM in villous vasculature rose significantly with gestational age. Villous vessels of IUGR placentae, showed a higher expression of TM, compared to placentae of appropriately grown fetus (p < 0.05). The number of terminal villi and the number of blood vessels per intermediate villi was significantly reduced in IUGR placentae (p < 0.05). These differences reflect inadequate vascularisation and impaired angiogenesis in IUGR.