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In 2023, 500 years have passed since the entry into force of the ordinary court procedure in Poland (formula processus iudiciarii, 1523), as well as 90 years since the unification of court procedures in Poland in general and 90 years since the entry into force of the first Polish Code of Civil Procedure (1933). Therefore, this is a special opportunity to refer, in this context, to the first transformation of procedural law in Poland in the 20th century, which took place after World War I, especially in the context of comparative procedural law issues. Applicability of foreign laws in the Polish territories after World War I: Russian, German, Austrian, and Hungarian (in a small area of Spisz and Orawa), as well as Polish-French legislation, gave rise to a complicated and territorial legal mosaic. The codification works undertaken at that time in Poland, unprecedented in Europe or even in the entire world, fell within a period of great development of comparative jurisprudence. They were profound comparative studies, which are proven by the published drafts, together with explanatory memorandums, offering an original synthesis of the legal thought. The considerations made in this article relate to procedural law, which was significantly diversified in the territory of Poland reborn in 1918, especially as regards the model of legal remedies, which gave rise to considerable difficulties in the practice of the system of justice prior to the unification of court procedures. Special attention was paid to the legal situation in the Silesian Voivodeship, being a peculiar microcosm of the legal situation in the entire country.

We propose that Frantz Fanon’s analysis of language develops an immanent critique of Maurice Merleau-Ponty’s phenomenology. Fanon transforms the phenomenological method to account for the Black speaking subjects’ experience through a sociogenic account of language. First, while the French colonial language has a robust diachronic dimension, the language of the colonized, Creole, is relegated to a synchrony without diachrony, as the historical past is erased. Second, while French metropolitan intersubjectivity is modelled on harmonious reciprocity and reflects continuity between the family and the state, relations between dominant and subjugated speaking subjects employ paternalism and primitivism that reinforce coloniality. We develop the notion of a racialized and historicized language-schema to capture Fanon’s analysis and envisage future critical phenomenologies of language.

Background: Statins and proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) are cornerstones of therapy to prevent cardiovascular disease, acting by lowering lipid concentrations and only partially identified pleiotropic effects. This study aimed to analyze impacts of atorvastatin and synthetic peptide PCSK9i on bioenergetics and function of microvascular endothelial cells and cardiomyocytes.Methods: Mitochondrial function and abundance as well as intracellular nucleotides, membrane potential, cytoskeleton structure, and cell proliferation rate were evaluated in mouse heart microvascular endothelial cells (H5V) and cardiomyocytes (HL-1) under normal and hypoxia-mimicking conditions (CoCl2 exposure).Results: In normal conditions PCSK9i, unlike atorvastatin, enhanced mitochondrial respiratory parameters, increased nucleotide levels, prevented actin cytoskeleton disturbances and stimulated endothelial cell proliferation. Under hypoxia-mimicking conditions both atorvastatin and PCSK9i improved the mitochondrial respiration and membrane potential in both cell types.Conclusion: This study demonstrated that both treatments benefited the endothelial cell and cardiomyocyte bioenergetics, but the effects of PCSK9i were superior.

Adenine nucleotides play a critical role in maintaining essential functions of red blood cells (RBCs), including energy metabolism, redox status, shape fluctuations and RBC-dependent endothelial and microvascular functions. Recently, it has been shown that infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) might lead to morphological and metabolic alterations in erythrocytes in both mild and severe cases of coronavirus disease (COVID-19). However, little is known about the effects of COVID-19 on the nucleotide energetics of RBCs nor about the potential contribution of nucleotide metabolism to the long COVID syndrome. This study aimed to analyze the levels of adenine nucleotides in RBCs isolated from patients 12 weeks after mild SARS-CoV-2 infection who suffered from long COVID symptoms and to relate them with the endothelial and microvascular function parameters as well as the rate of peripheral tissue oxygen supply. Although the absolute quantities of adenine nucleotides in RBCs were rather slightly changed in long COVID individuals, many parameters related to the endothelial and microcirculatory function showed significant correlations with RBC adenosine triphosphate (ATP) and total adenine nucleotide (TAN) concentration. A particularly strong relationship was observed between ATP in RBCs and the serum ratio of arginine to asymmetric dimethylarginine—an indicator of endothelial function. Consistently, a positive correlation was also observed between the ATP/ADP ratio and diminished reactive hyperemic response in long COVID patients, assessed by the flow-mediated skin fluorescence (FMSF) technique, which reflected decreased vascular nitric oxide bioavailability. In addition, we have shown that patients after COVID-19 have significantly impaired ischemic response parameters (IR max and IR index), examined by FMSF, which revealed diminished residual bioavailability of oxygen in epidermal keratinocytes after brachial artery occlusion. These ischemic response parameters revealed a strong positive correlation with the RBC ATP/ADP ratio, confirming a key role of RBC bioenergetics in peripheral tissue oxygen supply. Taken together, the outcomes of this study indicate that dysregulation of metabolic processes in erythrocytes with the co-occurring endothelial and microvascular dysfunction is associated with diminished intracellular oxygen delivery, which may partly explain long COVID-specific symptoms such as physical impairment and fatigue.

The subject of this paper are those factual states that occurred on the basis of the agrarian reform decree and concerned the unlawful seizure by the State of palace-park complexes. It was only after the collapse of real socialism in 1989 that the owners or their legal successors obtained an annulment of the decision to seize the property. However, this was, and is, only the beginning of the struggle, as the State Treasury or its legal successors are claiming before the common courts the acquisitive prescription of the property being the subject to the recovery claim. The divergence of at least 20 years in jurisprudence as to the date of commencement of the period required for acquisitive prescription (1980–1991) is an undesirable phenomenon, requiring the adoption of a coherent approach of the courts. Consequently, the authors of this text represent the view that the period of validity of both the Agrarian Reform Decree and the subsequent legal acts, with particular emphasis on the period of validity of the Decree of 1945 (Journal of Laws no. 28, item 321) and then Article 9 (16) of the Act of 1958 excluded the course of the acquisitive prescription in favour of the State Treasury of the agricultural and forestry properties unlawfully seized by the State. This period lasted until 31 December 1991, i.e. until the final date when Article 9 (16) was in force.

Objectives: Experimental models to test the effective protection against cardiac ischemia injury are still challenging in pre-clinical studies. The use of myocardial slices creates a special link between testing isolated cardiomyocytes and whole-heart research. In this work, we investigated the effects of oxygen deprivation in a hypoxic chamber and treatment with cobalt chloride (CoCl2) on the nucleotide profile in isolated mouse myocardial slices. Methods: 200 μm-thick left ventricle myocardial slices were obtained from 3-month-old male C57Bl/6J mice using an oscillatory microtome. Slices were then exposed to 1% O2 atmosphere or 100 μM CoCl2 at 37 °C for 45 min and used for nucleotide measurements using ultra-high-performance liquid chromatography. The effects of two short-term experimental models of hypoxia were compared to 2′-deoxyglucose with oligomycin (2-DG + OLIGO) treatment, which inhibited both glycolysis and mitochondrial ATP synthesis. Key findings: A significant effect of hypoxia with 1% O2 was observed on adenosine triphosphate (ATP) and total adenine nucleotide (TAN) concentrations as well as on adenylate energy charge (AEC), ATP/ADP and ATP/AMP ratios. Oxygen deprivation caused changes almost as profound as 2-DG + OLIGO, emphasizing the critical role of mitochondrial oxidative phosphorylation in the energy metabolism of cultured heart slices. CoCl2 treatment that elicits hypoxia-like responses via HIF-1α stabilization only slightly affected nucleotide levels. This suggests that mechanisms induced by cobalt ions require more time to change the cardiac energy metabolism. Conclusions: A short-term culture of myocardial slices in a hypoxic chamber seems to be an appropriate model of cardiac ischemia for testing new pharmacological approaches based on modulating the energy metabolism of cardiac cells. [ABSTRACT FROM AUTHOR]

Background: Food–drug interactions (FDIs) may alter drug pharmacokinetics and pharmacodynamics, modifying the whole therapy's effectiveness. Some of them cause the attenuation of drug effects, while others inhibit the medicines' metabolism resulting, in too high concentrations of the medicine in the body. Thus, some healthcare professionals—doctors, pharmacists or dieticians—should be aware of the possibility of food–drug interactions. This study aimed to assess knowledge of food–drug interactions among students of pharmacy, medicine, stomatology, medical analysis and dietetics and students of the college of further medical education for pharmacy technicians. Methods: Students (n = 820) completed a custom-made questionnaire. The relationships between the continuous variables were analysed on the basis of Pearson's correlation coefficient. To verify the predictors of objective students' knowledge about food–drug interactions, a multiple linear regression model with analysis of covariance (ANCOVA) was used. The Kruskal–Wallis test was performed to compare the total scores the respondents received for questions assessing their objective knowledge of FDI. Results: Students' objective knowledge of FDIs correlated positively with their year of study and their self-evaluation of it. It was also significantly influenced by the field and mode of studies and by the fact that the issue had been discussed during the courses. Conclusions: Most students of the medical university had serious deficiencies in their knowledge of food–drug interactions. This is of particular concern for future doctors and dentists. Among the respondents, pharmacy students stood out, as their FDI knowledge was greater. The issue of food–drug interactions should be more widely taught at medical universities, which was emphasised by the respondents themselves. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) hold great promise for clinical application as new diagnostic and therapeutic modalities. This paper describes major GMP-based upstream and downstream manufacturing processes for EV large-scale production, also focusing on post-processing technologies such as surface bioengineering and uploading studies to yield novel EV-based diagnostics and advanced therapy medicinal products. This paper also focuses on the quality, safety, and efficacy issues of the bioengineered EV drug candidates before first-in-human studies. Because clinical trials involving extracellular vesicles are on the global rise, this paper encompasses different clinical studies registered on clinical-trial register platforms, with varying levels of advancement, highlighting the growing interest in EV-related clinical programs. Navigating the regulatory affairs of EVs poses real challenges, and obtaining marketing authorization for EV-based medicines remains complex due to the lack of specific regulatory guidelines for such novel products. This paper discusses the state-of-the-art regulatory knowledge to date on EV-based diagnostics and medicinal products, highlighting further research and global regulatory needs for the safe and reliable implementation of bioengineered EVs as diagnostic and therapeutic tools in clinical settings. Post-marketing pharmacovigilance for EV-based medicinal products is also presented, mainly addressing such topics as risk assessment and risk management. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the effect of genistein on the level of cholesterol, oxysterols, and composition of fatty acids, as well as enzymatic activity of desaturases, in rats with breast cancer. The animals were supplemented with nano-, micro-, and macrogenistein. Rats were treated with 7,12-dimethylbenz[a]anthracene to induce mammary adenocarcinoma. In the case of animals supplemented with genistein, an increase in the intensity of the carcinogenesis process was observed. Genistein supplementation also affected the cholesterol and oxysterols levels, as well as the composition of fatty acids, in the serum of rats with neoplastic disease. Dietary supplementation with nanogenistein significantly increased the level of cholesterol (p = 0.02) and cholesterol oxidation products (p = 0.02), which may have significant impacts on cancer development and progression.

The present study aimed to assess the levels of 98 multi-class pharmaceuticals including cardiovascular drugs, antidepressants, hypnotics, antibiotics, and sulfonamides occurring in the muscle tissue of fish caught in the Baltic Sea. The following fish species were collected: perch (Perca fluviatilis); flounder (Platichthys flesus); turbot (Scophthalmus maximus); plaice (Pleuronectes platessa); cod (Gadus morhua callarias); bream (Abramis brama); crucian (Carassius carassius). Additionally, in the examined fish muscle the levels of heavy metals and trace elements were determined (As; Ag; Au; Ba; Cd; Co; Cr; Cu; Hg; Li; Mo; Ni; Pb; Sb; Se; Sn; Tl; V) as well as the levels of cholesterol and its 5 derivatives (7-ketocholesterol; 7α-hydroxycholesterol; 7β-hydroxycholesterol; 5β,6β-epoxy-cholesterol; 5α,6α-epoxycholesterol). In the performed studies 11 out of 98 examined pharmaceuticals were detected in fish muscle. The levels of pharmaceuticals in fish muscle varied depending on the species. In the tissues of bream and crucian, no pharmaceuticals were found. Mercury, lead and arsenic were detected in the muscles of all examined fish. Based on the hazard factor for Hg, Pb, Cd, Ni (target hazard quotient, THQ < 1), it was found that the consumption of the studied fish does not constitute a health risk. However, the THQ for As remained >1 indicated possible risk from those metals. In the examined fish muscle the total cholesterol oxidation products (COPs) level of oxysterols were, respectively: 6.90 (cod) μg/g–4.18 μg/g (perch), which corresponded to 0.7–1.5% of cholesterol. The main COPs evaluated were 7-ketocholesterol (0.78 ± 0.14–1.79 ± 0.06 μg/g), 7β-hydroxycholesterol (0.50 ± 0.04–3.20 ± 2.95 μg/g) and 5β,6β-epoxycholesterol (0.66 ± 0.03–1.53 ± 0.66 μg/g). The assessment of health hazards due to contaminations is necessary, which may help to introduce national legislation and global standards aimed at reducing or even eliminating the exposure to contaminants.

Pomegranate seed oil (PSO) and bitter melon dried fruits (BME) are used as natural remedies in folk medicine and as dietary supplements. However, the exact mechanism of their beneficial action is not known. The aim of study was to assess how the diet supplementation with PSO and/or with an aqueous solution of Momordica charantia affects the metabolism of fatty acids, fatty acids composition and the level of prostaglandin E2 (PGE2) in rat liver. Animals (Sprague-Dawley female rats, n = 48) were divide into four equinumerous groups and fed as a control diet or experimental diets supplemented with PSO, BME or both PSO and BME for 21 weeks. Fatty acids were determined using gas chromatography with flame ionization detection. PSO added to the diet increased the rumenic acid content (p < 0.0001) and increased accumulation of n-6 fatty acids (p = 0.0001) in hepatic tissue. Enrichment of the diet either with PSO or with BME reduced the activity of Δ6-desaturase (D6D) (p = 0.0019), whereas the combination of those dietary factors only slightly increased the effect. Applied dietary supplements significantly reduced the PGE2 level (p = 0.0021). No significant intensification of the influence on the investigated parameters resulted from combined application of PSO and BME. PSO and BME have potential health-promoting properties because they influence fatty acids composition and exhibit an inhibiting effect on the activity of desaturases and thus they contribute to the reduction in the metabolites of arachidonic acid (especially PGE2).

The inverse correlation observed between Alzheimer’s disease (AD) and cancer has prompted us to look for cholinesterase-inhibiting activity in phenothiazine derivatives that possess anticancer properties. With the use of in silico and in vitro screening methods, our study found a new biological activity in anticancer polycyclic, tricyclic, and tetracyclic compounds. The virtual screening of a library of 120 ligands, which are the derivatives of azaphenothiazine, led to the identification of 25 compounds that can act as potential inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Biological assays revealed the presence of selective inhibitors of eeAChE (electric eel AChE) or eqBuChE (equine serum BuChE) and nonselective inhibitors of both enzymes among the tested compounds. Their potencies against eeAChE were in a submicromolar-to-micromolar range with IC50 values from 0.78 to 19.32 μM, while their IC50 values against eqBuChE ranged from 0.46 to 10.38 μM. The most potent among the compounds tested was the tetracyclic derivative, 6-(4-diethylaminobut-2-ynyl)-9-methylthioquinobenzothiazine 24, which was capable of inhibiting both enzymes. 9-Fluoro-6-(1-piperidylethyl)quinobenzothiazine 23 was found to act as a selective inhibitor of eqBuChE with an IC50 value of 0.46 μM. Compounds with such a dual antitumor and cholinesterase-inhibitory activity can be considered as a valuable combination for the treatment of both cancer and AD prevention. The results presented in this study might open new directions of research on the group of tricyclic phenothiazine derivatives.