This article is an analysis of two conceptions of both awareness of other persons and relations with them put forward by Michel Henry and Marc Richir – philosophers who are associated with “new ...phenomenology in France”. My aim is to show how they reinterpret Husserl’s view of intersubjectvity and attempt to solve the issues related to traditional phenomenological solution. Thanks to rejecting Husserl’s notion of intentionality, they provide a new ground for analysis. The originality of their account lies in an introduction of the very notion of passivity (Henry) and transcedental interfacticity (Richir). In spite of some differences between them, they can be considered as ideas that shed a new light on the problem of intersubjectivity in phenomenology.
The early detection of metastasis based on biomarkers in plasma may improve cancer prognosis and guide treatment. The aim of this work was to characterize alterations in metabolites of the arginine ...pathway, energy metabolism, and structural and signalling lipids in plasma in the early and late stages of murine breast cancer metastasis.
Mice were orthotopically inoculated with 4T1 metastatic breast cancer cells, and plasma was analysed along the pulmonary metastasis progression using LC-MS/MS-based targeted metabolomics and lipidomics.
Based on primary tumour growth and pulmonary metastases, 1-2 weeks after 4T1 cancer cell inoculation was defined as an early metastatic stage, and 3-4 weeks after 4T1 cancer cell inoculation was defined as a late metastatic stage. Early metastasis was featured in plasma by a shift of L-arginine metabolism towards arginase (increased ornithine/arginine ratio) and polyamine synthesis (increased putrescine). Late metastasis was reflected in plasma by further progression of changes in the arginine pathway with an additional increase in asymmetric dimethylarginine plasma concentration, as well as by a profound energy metabolism reprogramming towards glycolysis, an accelerated pentose phosphate pathway and a concomitant decrease in tricarboxylic cycle rate ("Warburg effect"). The late but not the early phase of metastasis was also characterized by a different lipid profile pattern in plasma, including a decrease in total phosphatidylcholines, a decrease in diester-bound phospholipid fraction and an increase in lysophospholipids associated with an increase in total sphingomyelins.
The early phase of metastasis in murine 4T1 metastatic breast cancer was associated with plasma metabolome changes characteristic of arginase activation and polyamine synthesis. The late metastasis was reflected in plasma not only by the alterations in arginine pathways but also by a shift towards glycolysis and the pentose pathway, remodelling of structural lipids and activation of lipid signalling, all of which coincided with metastasis progression.
For physical vapor deposition (PVD) technology, cleaning a substrate is one of the key preliminary processes before depositing the metal layer. In this article, we present the results of research on ...the modification of a textile composite substrate using laser technology and its influence on the surface resistance of silver structures intended for use in wearable electronics. As a result of the substrate modification, the resistance of the layers increased as compared with the structures produced on an unmodified substrate. An experimental planning technique was used to optimize the laser modification process.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The need for physical distancing due to COVID-19 mitigation efforts forced prolonged social isolation, which may affect sleep and lead to mental health problems. Previous research has shown that ...young adults are particularly vulnerable to psychological stress caused by social isolation, the negative psychological impact of the pandemic, and greater frequency and severity of sleep problems. Therefore, the main goal of the present study was to examine whether insomnia could constitute a mediation mechanism that explains the relationship between social isolation experienced during the COVID-19 pandemic and mental health outcomes (depression and anxiety) reported up to 1.5 years later. The study was conducted among young (M±SD; 24.08±3.75) men (N = 1025) in Poland. Data were collected by means of self-report questionnaires, including The Social Isolation Index, The Athens Insomnia Scale, The State-Trait Anxiety Inventory (STAI-S) and Beck's Depression Inventory (BDI-II). The results show that insomnia mediates the relationships between social isolation and both anxiety and depression. The current findings emphasize the role of insomnia in the relationships between social isolation experienced during COVID-19 and negative emotional states. From a clinical perspective, the results suggest that implementing therapeutic components that address social isolation in insomnia treatment programs may prevent the development of depression and anxiety symptoms among young men.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background The impairment of endothelium-dependent vasodilation, increased endothelial permeability, and glycocalyx degradation are all important pathophysiological components of endothelial ...dysfunction. However, it is still not clear whether in atherosclerosis, glycocalyx injury precedes other features of endothelial dysfunction or these events coincide. Methods and Results Herein, we demonstrate that in 4- to 8-week-old apolipoprotein E/low-density lipoprotein receptor-deficient mice, at the stage before development of atherosclerotic plaques, impaired acetylcholine-induced vasodilation, reduced NO production in aorta, and increased endothelial permeability were all observed; however, flow-mediated dilation in the femoral artery was fully preserved. In 4-week-old mice, glycocalyx coverage was reduced and endothelial stiffness was increased, whereas glycocalyx length was significantly decreased at 8 weeks of age. Early changes in endothelial function were also featured by increased plasma concentration of biomarkers of glycocalyx disruption (endocan), biomarkers of endothelial inflammation (soluble vascular cell adhesion molecule 1), increased vascular permeability (angiopoietin 2), and alterations in hemostasis (tissue plasminogen activator and plasminogen activator inhibitor 1). In 28-week-old mice, at the stage of advanced atherosclerotic plaque development, impaired NO production and nearly all other features of endothelial dysfunction were changed to a similar extent, compared with the preatherosclerotic plaque phase. The exceptions were the occurrence of acetylcholine-induced vasoconstriction in the aorta and brachiocephalic artery, impaired flow-mediated vasodilation in the femoral artery, and further reduction of glycocalyx length and coverage with a concomitant further increase in endothelial permeability. Conclusions In conclusion, even at the early stage before the development of atherosclerotic plaques, endothelial dysfunction is a complex multifactorial response that has not been previously appreciated.
The endothelium plays an important role in cancer metastasis, but the mechanisms involved are still not clear. In the present work, we characterised the changes in endothelial function at early and ...late stages of breast cancer progression in an orthotopic model of murine mammary carcinoma (4T1 cells). Endothelial function was analysed based on simultaneous microflow liquid chromatography-tandem mass spectrometry using multiple reaction monitoring (microLC/MS-MRM) quantification of 12 endothelium-related biomarkers, including those reflecting glycocalyx disruption - syndecan-1 (SDC-1), endocan (ESM-1); endothelial inflammation - vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), E-selectin (E-sel); endothelial permeability - fms-like tyrosine kinase 1 (FLT-1), angiopoietin 2 (Angpt-2); and haemostasis - von Willebrand factor (vWF), tissue plasminogen activator (t-PA), plasminogen activator inhibitor 1 (PAI-1), as well as those that are pathophysiologically linked to endothelial function - adrenomedullin (ADM) and adiponectin (ADN). The early phase of metastasis in mouse plasma was associated with glycocalyx disruption (increased SDC-1 and ESM-1), endothelial inflammation increased soluble VCAM-1 (sVCAM-1) and increased vascular permeability (Angpt-2). During the late phase of metastasis, additional alterations in haemostasis (increased PAI-1 and vWF), as well as a rise in ADM and substantial fall in ADN concentration, were observed. In conclusion, in a murine model of breast cancer metastasis, we identified glycocalyx disruption, endothelial inflammation and increased endothelial permeability as important events in early metastasis, while the late phase of metastasis was additionally characterised by alterations in haemostasis.
Textiles require finishing to improve their usability and functionality but in the first place, to reduce of pilling tendency, which affects all kinds of synthetic and natural fabrics. Several laser ...ablation tests have been applied to the selected fabrics with different chemical composition to reveal the impact of this process on the pilling behavior. To reflect the pilling changes, two textural descriptors have been proposed to textile images obtained with optical coherence tomography (OCT). They showed the trend to reduce values with increasing laser power applied to the tested fabrics. It has been demonstrated, that in the case of textiles based on polyester threads, laser modification of the product surface led to a significant reduction in their tendency for pilling.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
This study aimed to extend the body of preclinical research on prototype dual-acting compounds combining the pharmacophores relevant for inhibiting cyclic nucleotide phosphodiesterase 10 (PDE10A) and ...serotonin 5-HT1A/5-HT7 receptor (5-HT1AR/5-HT7R) activity into a single chemical entity (compounds PQA-AZ4 and PQA-AZ6). After i.v. administration of PQA-AZ4 and PQA-AZ6 to rats, the brain to plasma ratio was 0.9 and 8.60, respectively. After i.g. administration, the brain to plasma ratio was 5.7 and 5.3, respectively. An antidepressant-like effect was observed for PQA-AZ6 in the forced swim test, after chronic 21-day treatment via i.p. administration with 1 mg/kg/day. Both compounds revealed an increased level of brain-derived neurotrophic factor (Bdnf) mRNA in the hippocampus and prefrontal cortex. Moreover, PQA-AZ4 and PQA-AZ6 completely reversed (+)-MK801-induced memory disturbances comparable with the potent PDE10 inhibitor, compound PQ-10. In the safety profile that included measurements of plasma glucose, triglyceride, and total cholesterol concentration, liver enzyme activity, the total antioxidant activity of serum, together with weight gain, compounds exhibited no significant activity. However, the studied compounds had different effects on human normal fibroblast cells as revealed in in vitro assay. The pharmacokinetic and biochemical results support the notion that these novel dual-acting compounds might offer a promising therapeutic tool in CNS-related disorders.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Abstract
Background
Protein disulphide isomerases (PDIs) play an important role in cancer progression. However, the relative contribution of the various isoforms of PDI in tumorigenesis is not clear.
...Methods
The content of PDI isoforms in 22 cancer cells lines was investigated using LC–MS/MS-based proteomic analysis. The effects of PDIA1, PDIA3 and PDIA17 inhibition on the proliferation, migration and adhesion of MCF-7 and MDA-MB-231 cells, identified as high and low PDIA17 expressing cells, respectively, were assessed using novel aromatic N-sulphonamides of aziridine-2-carboxylic acid derivatives as PDI inhibitors.
Results
PDIA1 and PDIA3 were the most abundant in cancer cell lysates and were also detected extracellularly in breast cancer cells (MDA-MB-231 and MCF-7). Some cancer cell lines (e.g., MCF-7, HT-29) showed upregulated expression of PDIA17, whereas in others (e.g., MDA-MB-231, 67NR), PDIA17 was not detected. The simultaneous inhibition of PDIA1 and PDIA3 showed similar anti-proliferative effects in MCF-7 and MDA-MB-231 breast cancer cells. However, the inhibition of PDIA1 and PDIA17 in the MCF-7 cell line resulted in more effective anti-adhesive and anti-proliferative effects.
Conclusions
PDIA1 and PDIA3 represent major isoforms of multiple cancer cells, and their non-selective inhibition displays significant anti-proliferative effects irrespective of whether or not PDIA17 is present. The more pronounced anti-adhesive effects of PDI inhibition in hormone-sensitive MCF-7 cells featured by higher levels of PDIs when compared to triple-negative MDA-MB-231 cells suggests that targeting extracellular PDIA1 and PDIA3 with or without additional PDIA17 inhibition may represent a strategy for personalized anti-adhesive, anti-metastatic therapy in cancers with high PDI expression.
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Background Long-term feeding with a high-fat diet (HFD) induces endothelial dysfunction in mice, but early HFD-induced effects on endothelium have not been well characterized. Methods and Results ...Using an magnetic resonance imaging-based methodology that allows characterization of endothelial function in vivo, we demonstrated that short-term (2 weeks) feeding with a HFD to
mice or to
mice resulted in the impairment of acetylcholine-induced response in the abdominal aorta (AA), whereas, in the thoracic aorta (TA), the acetylcholine-induced response was largely preserved. Similarly, HFD resulted in arterial stiffness in the AA, but not in the TA. The difference in HFD-induced response was ascribed to distinct characteristics of perivascular adipose tissue in the TA and AA, related to brown- and white-like adipose tissue, respectively, as assessed by histology, immunohistochemistry, and Raman spectroscopy. In contrast, short-term HFD-induced endothelial dysfunction could not be linked to systemic insulin resistance, changes in plasma concentration of nitrite, or concentration of biomarkers of glycocalyx disruption (syndecan-1 and endocan), endothelial inflammation (soluble form of vascular cell adhesion molecule 1, soluble form of intercellular adhesion molecule 1 and soluble form of E-selectin), endothelial permeability (soluble form of fms-like tyrosine kinase 1 and angiopoietin 2), and hemostasis (tissue plasminogen activator and plasminogen activator inhibitor 1). Conclusions Short-term feeding with a HFD induces endothelial dysfunction in the AA but not in the TA, which could be ascribed to a differential response of perivascular adipose tissue to a HFD in the AA versus TA. Importantly, early endothelial dysfunction in the AA is not linked to elevation of classical systemic biomarkers of endothelial dysfunction.
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