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Anna Wróblewska, Agnieszka Szczygieł, Bożena Szermer-Olearnik, Elżbieta Pajtasz-Piasecka Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, PolandCorrespondence: Anna Wróblewska, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, Wrocław, 53-114, Poland, Tel +48 71 3709928, Email anna.wroblewska@hirszfeld.plAbstract: Macrophages play a critical role in the immune response due to their ability to recognize and remove pathogens, as well as present antigens, which are involved in inflammation, but they are also one of the most abundant immune cell populations present in the tumor microenvironment. In recent years, macrophages have become promising cellular carriers for drug and nanoparticle delivery to the tumor microenvironment, mainly due to their natural properties such as biocompatibility, degradability, lack of immunogenicity, long half-life in circulation, crossing biological barriers, and the possibility of migration and accumulation at a site of inflammation such as a tumor. For the effectiveness of this therapeutic strategy, known as “Trojan horse”, it is important that the nanoparticles engulfed by macrophages do not affect their proper functioning. In our review, we discussed how the size, shape, chemical and mechanical properties of nanoparticles influence their internalization by macrophages. In addition, we described the promising research utilizing macrophages, their cell membranes and macrophage-derived exosomes as drug carriers in anticancer therapy. As a prospect of the wider use of this therapeutic strategy, we postulate its future application in boron delivery to the tumor environment in boron neutron capture therapy.Keywords: macrophages, cellular carriers, anticancer therapy, tumor microenvironment, boron neutron capture therapy

Abstract Background Eliminating hepatitis C virus (HCV) infections is a goal set by the World Health Organization. This has become possible with the introduction of highly effective and safe direct-acting antivirals (DAA) but limitations remain due to undiagnosed HCV infections and loss of patients from the cascade of care at various stages, including those lost to follow-up (LTFU) before the assessment of the effectiveness of the therapy. The aim of our study was to determine the extent of this loss and to establish the characteristics of patients experiencing it. Methods Patients with chronic HCV infection from the Polish retrospective multicenter EpiTer-2 database who were treated with DAA therapies between 2015 and 2023 were included in the study. Results In the study population of 18,968 patients, 106 had died by the end of the 12-week post-treatment follow-up period, and 509 patients did not report for evaluation of therapy effectiveness while alive and were considered LTFU. Among patients with available assessment of sustained virological response (SVR), the effectiveness of therapy was 97.5%. A significantly higher percentage of men (p

Abstract Background The use of cells as carriers for the delivery of nanoparticles is a promising approach in anticancer therapy, mainly due to their natural properties, such as biocompatibility and non-immunogenicity. Cellular carriers prevent the rapid degradation of nanoparticles, improve their distribution, reduce cytotoxicity and ensure selective delivery to the tumor microenvironment. Therefore, we propose the use of phagocytic cells as boron carbide nanoparticle carriers for boron delivery to the tumor microenvironment in boron neutron capture therapy. Results Macrophages originating from cell lines and bone marrow showed a greater ability to interact with boron carbide (B4C) than dendritic cells, especially the preparation containing larger nanoparticles (B4C 2). Consequently, B4C 2 caused greater toxicity and induced the secretion of pro-inflammatory cytokines by these cells. However, migration assays demonstrated that macrophages loaded with B4C 1 migrated more efficiently than with B4C 2. Therefore, smaller nanoparticles (B4C 1) with lower toxicity but similar ability to activate macrophages proved to be more attractive. Conclusions Macrophages could be promising cellular carriers for boron carbide nanoparticle delivery, especially B4C 1 to the tumor microenvironment and thus prospective use in boron neutron capture therapy. Graphical Abstract

This research investigates energy poverty among social assistance beneficiaries in the Masovian Voivodeship, focusing on both objective and subjective dimensions. Energy poverty, characterized by the inability to afford adequate energy services, is examined through the Low Income High Cost (LIHC) measure and respondents’ subjective experiences. The study, based on a 2023 survey of 625 individuals, compares the Warsaw Capital Region and the Masovian Regional Region within the voivodeship. Results reveal that a significant proportion of beneficiaries face challenges in meeting energy needs, with 75% exceeding the 10% LIHC threshold. Strategies for coping include relying on social assistance, limiting current needs, seeking help from relatives, and dressing appropriately for indoor temperatures. The research covers energy poverty with economic, social, and health factors, emphasizing the need for targeted interventions and financial support mechanisms. Findings also highlight the impact of energy prices, varied energy consumption patterns, and subjective perceptions of energy poverty. The study contributes valuable insights into the complex phenomenon of energy poverty among social assistance recipients in the region.

In this study, we focus on the perspectives of social assistance beneficiaries and their reactions to the uncertainties arising from the war in Ukraine and the influx of war refugees in Poland. Our analysis is based on survey data collected from a representative sample of 1,057 social assistance beneficiaries in Poland’s central Mazowieckie region. Most respondents anticipate an increase in household poverty levels, a deterioration of Poland’s economic situation, and a decline in their own financial well-being due to the war in Ukraine. Expectations include a decrease in government revenue and a drop in household incomes. While our analyses offer a partial glimpse into the reality of social assistance beneficiaries in the Mazowieckie region, they underscore concerns about the potential impact of the refugee influx on both individual and national economic conditions. Addressing these concerns is crucial to prevent tensions between Poles and Ukrainians, highlighting the importance of recommendations to counteract discrimination and anti-refugee attitudes in the host society.

The use of nanoparticles in the industry carries the risk of their release into the environment. Based on the presumption that the primary graphene oxide (GO) toxicity mechanism is reactive oxygen species production in the cell, the question arises as to whether well-known antioxidants can protect the cell or significantly reduce the effects of GO. This study focused on the possible remedial effect of vitamin C in Acheta domesticus intoxicated with GO for whole lives. The reproduction potential was measured at the level of Vitellogenin (Vg) gene expression, Vg protein expression, hatching success, and share of nutrition in the developing egg. There was no simple relationship between the Vg gene’s expression and the Vg protein content. Despite fewer eggs laid in the vitamin C groups, hatching success was high, and egg composition did not differ significantly. The exceptions were GO20 and GO20 + Vit. C groups, with a shift in the lipid content in the egg. Most likely, ascorbic acid impacts the level of Vg gene expression but does not affect the production of Vg protein or the quality of eggs laid. Low GO concentration in food did not cause adverse effects, but the relationship between GO toxicity and its concentration should be investigated more thoroughly.

Background: It is essential to identify novel non-invasive markers of liver fibrosis for clinical and scientific purposes. Thus, the goal of our survey was to assess the serological expression of selected microRNAs (miRNAs) in patients with alcohol-related liver cirrhosis (ALC) and to correlate them with other existing markers. Methods: Two hundred and thirty-nine persons were enrolled in the study: one hundred and thirty-nine with ALC and one hundred healthy controls. Serological expression of miR-126-3p, miR-197-3p and miR-1-3p was evaluated in all participants. Direct markers of liver fibrosis (PICP, PIIINP, PDGF-AB, TGF-α and laminin) together with indirect indices (AAR, APRI, FIB-4 and GPR) were also assessed. The additional evaluation concerned hematological parameters: MPV, PDW, PCT, RDW, MPR, RPR NLR, PLR and RLR. Results: The expression of miR-197-3p was lower in ALC compared to controls (p < 0.0001). miR-126-3p correlated negatively with AST (p < 0.05) and positively with miR-197-3p (p < 0.001). miR-197-3p correlated with direct markers of liver fibrosis—positively with PDGF-AB (p < 0.005) and negatively with TGF-α (p < 0.01). Significant negative relationships were noticed between miR-1-3p and the number of neutrophils (p < 0.05), TGF-α (p < 0.05) and laminin (p < 0.05). Conclusions: The achieved results and observed correlations prove the potential involvement of the examined miRNAs in the process of liver fibrosis, giving a novel insight into the diagnostics of liver cirrhosis.

Background: Inflammatory demyelination and impaired recovery processes result in permanent neurodegeneration and neurological disability in patients with multiple sclerosis (MS). In terms of smoldering MS, chronic neuroinflammation develops in the early period of the disease and leads to confirmed disability accumulation. There is a great need to identify biomarkers of neurodegeneration and disease progression. Methods: A single-center prospective observational study was performed. The median age of the patients was 40 (31–52) years. Women comprised 64% of the study population. We evaluated the concentrations of the parameters of brain injury (NF-H, GFAP, S100B and UCHL1) in the cerebrospinal fluid (CSF) and the selected interleukins (ILs) in serum of 123 relapsing–remitting MS (RRMS) and 88 progressive MS (PMS) patients. Results: The levels of GFAP, S100B and UCHL were higher in the PMS group than the RRMS group, in contrast to the levels of NF-H. We observed a positive correlation between the selected pro-inflammatory cytokines and the parameters of brain injury. The Expanded Disability Status Scale (EDSS) score increased with GFAP and NF-H levels and was correlated with the selected ILs. The concentrations of S100B, UCHL1 and NF-H reflected the duration of MS symptoms. Conclusions: The levels of brain injury parameters in the CSF and the selected serum ILs in MS patients seem to be promising biomarkers to determine neurodegeneration and neuroinflammation in smoldering MS. Further studies are warranted in this respect.

Molds pose a severe challenge to agriculture because they cause very large crop losses. For this reason, synthetic fungicides have been used for a long time. Without adequate protection against pests and various pathogens, crop losses could be as high as 30–40%. However, concerns mainly about the environmental impact of synthetic antifungals and human health risk have prompted a search for natural alternatives. But do natural remedies only have advantages? This article reviews the current state of knowledge on the use of antifungal substances in agriculture to protect seeds against phytopathogens. The advantages and disadvantages of using both synthetic and natural fungicides to protect cereal grains were discussed, indicating specific examples and mechanisms of action. The possibilities of an integrated control approach, combining cultural, biological, and chemical methods are described, constituting a holistic strategy for sustainable mold management in the grain industry.

Ophidiomyces ophidiicola, the causative agent of ophidiomycosis, poses a potential threat to wild snakes worldwide. This study aimed to retrospectively investigate the prevalence of O. ophidiicola in archived snake moults collected from the San River Valley in the Bieszczady Mountains, Poland, from 2010 to 2012. Using qPCR for O. ophidiicola detection and conventional PCR for clade characterisation, we analysed 58 moults and one road-killed specimen of Zamenis longissimus and Natrix natrix. A novel combination of primers (ITS2L) was used to simultaneously confirm SYBR Green-based qPCR results and perform genotyping. O. ophidiicola has been detected from two Z. longissimus and one N. natrix specimens. The identified clade (I-B) is consistent with those found in wild snakes of eastern Europe and San River Valley, indicating that O. ophidiicola has been present in this region for at least a decade. This study underscores the value of historical samples in understanding the long-term presence of pathogens and highlights the potential role of environmental reservoirs in the persistence of O. ophidiicola. Our findings are crucial for informing conservation strategies for the endangered Aesculapian snake populations in Poland, emphasising the need for ongoing monitoring and habitat management to mitigate the potential impact of ophidiomycosis.

There is increasing evidence that vitamin D (VitD) supplementation may reduce inflammation in individuals with multiple sclerosis (MS). The aim of this study was to evaluate the effect of different doses of VitD on selected markers of inflammation in patients with relapsing–remitting MS (RRMS). Participants were divided depending on the supplemented dose of VitD into a high-dose (2000 IU/d; HD) group and a low-dose (15,960 IU/month; LD) group (n = 23 and n = 29, respectively). The concentration of 25(OH)D and the levels of CXCL16, PTX3, ALCAM, IL-1RA, and OPG were measured initially and after six months of VitD supplementation in blood serum. A significant increase in the concentrations of CXCL16, PTX3, and OPG was observed during the study (p = 0.02, p = 0.01, and p < 0.01, respectively). Furthermore, a higher increase in PTX3 and OPG in the LD group was observed (p = 0.04 and p = 0.03, respectively). A significant positive correlation was observed between the 25(OH)D serum concentration and PTX3 (R = 0.28, p < 0.05) and OPG (R = 0.28, p < 0.05) only at the beginning of the study. In patients with RRMS, such doses of VitD might be too low to induce obvious beneficial effects on the pro-inflammatory and inflammatory balance.

Cytokines regulate immune responses and are crucial to MS pathogenesis. This study evaluated pro-inflammatory and anti-inflammatory cytokine concentrations in the CSF of de novo diagnosed RRMS patients compared to healthy controls. We assessed cytokine levels in the CSF of 118 de novo diagnosed RRMS patients and 112 controls, analyzing relationships with time from symptom onset to diagnosis, MRI lesions, and serum vitamin D levels. Elevated levels of IL-2, IL-4, IL-6, IL-13, FGF-basic, and GM-CSF, and lower levels of IL-1β, IL-1RA, IL-5, IL-7, IL-9, IL-10, IL-12p70, IL-15, G-CSF, PDGF-bb, and VEGF were observed in RRMS patients compared to controls. IL-2, IL-4, IL-12p70, PDGF, G-CSF, GM-CSF, and FGF-basic levels increased over time, while IL-10 decreased. IL-1β, IL-1RA, IL-6, TNF-α, and PDGF-bb levels negatively correlated with serum vitamin D. TNF-α levels positively correlated with post-contrast-enhancing brain lesions. IL-15 levels negatively correlated with T2 and Gd(+) lesions in C-spine MRI, while TNF-α, PDGF-bb, and FGF-basic correlated positively with T2 lesions in C-spine MRI. IL-6 levels positively correlated with post-contrast-enhancing lesions in Th-spine MRI. Distinct cytokine profiles in the CSF of de novo diagnosed MS patients provide insights into MS pathogenesis and guide immunomodulatory therapy strategies.

Animal tumors serve as reasonable models for human cancers. Both human and animal tumors often reveal triplet EPR signals of nitrosylhemoglobin (HbNO) as an effect of nitric oxide formation in tumor tissue, where NO is complexed by Hb. In search of factors determining the appearance of nitrosylhemoglobin (HbNO) in solid tumors, we compared the intensities of electron paramagnetic resonance (EPR) signals of various iron–nitrosyl complexes detectable in tumor tissues, in the presence and absence of excess exogenous iron(II) and diethyldithiocarbamate (DETC). Three types of murine tumors, namely, L5178Y lymphoma, amelanotic Cloudman S91 melanoma, and Ehrlich carcinoma (EC) growing in DBA/2 or Swiss mice, were used. The results were analyzed in the context of vascularization determined histochemically using antibodies to CD31. Strong HbNO EPR signals were found in melanoma, i.e., in the tumor with a vast amount of a hemorrhagic necrosis core. Strong Fe(DETC)2NO signals could be induced in poorly vascularized EC. In L5178Y, there was a correlation between both types of signals, and in addition, Fe(RS)2(NO)2 signals of non-heme iron–nitrosyl complexes could be detected. We postulate that HbNO EPR signals appear during active destruction of well-vascularized tumor tissue due to hemorrhagic necrosis. The presence of iron–nitrosyl complexes in tumor tissue is biologically meaningful and defines the evolution of complicated tumor–host interactions.

The present study was to develop and validate a rapid analytical method of high-performance liquid chromatography with UV (HPLC/UV) detection for the determination of levetiracetam (LEV) concentration in human serum and cerebrospinal fluid (CSF) samples. The newly developed method was used to measure LEV concentration in the serum/CSF of 29 patients with different types of epilepsy; 52% (group I, n = 15) were treated with LEV in monotherapy, 48% (group II, n = 14) were co-administered with other AEDs. Serum and CSF levels of LEV were correlated with patients dosage, concomitant AEDs, therapeutic effect, and adverse drug reactions (ADRs). The calibration curves for serum and CSF were linear in the range 0.5-100 and 0.5-50 mg/L, respectively, with a coefficient correlation (R) value > 0.998 in each case. The quantitation limit was 0.5 mg/L in serum and CSF. The validated method was found to be selective, precise, and accurate. Optimal Cssmin values according to International League Against Epilepsy (12-46 mg/L) were achieved in 40 and 50% of patients in group I and II, and did not correlate with treatment efficacy in 27 and 21% patients, respectively. The ratio of serum LEV to CSF concentration (Kp) after 2 h administration LEV ranged in group I from 0.31 to 0.92 and in group II from 0.18 to 0.65. These findings indicate that the developed simple and rapid HPLC/UV method may be useful for monitoring serum/CSF LEV concentrations in patients receiving standard doses.

The article aims to demonstrate the role of the public policy clause in the Polish legal system in the context of matrimonial relations, with a particular emphasis on the institution of the conclusion and dissolution of marriage. As a part of the discussion, the analysis reconstructs the essence of the public policy clause, while demonstrating the most important principles of family law and conflict-of-law rules concerning matrimonial matters. The author examines the relationship between the public policy clause and family law by emphasising differences in legal systems amongst different nations and specifying the authorised and prohibited implementation of the public policy clause regarding marriage conclusion and dissolution. It is also pointed out that child marriage, polygamy, and divorce through unilateral declaration of will, cannot be reconciled with Polish public order; and attention is drawn to the inadmissibility of establishing restrictions on the freedom to marry on the basis of racial, religious and social criteria. The author’s evaluation utilises case law, academic literature, and opinions from doctrinal representatives on this issue. The conclusion emphasises the significance of the public policy clause in preserving the consistency and uniformity of the Polish legal system as a tool to fight discrimination and gender inequality.

Edmund Krzymuski’s Final Paper in the Work of the Section of Substantive Criminal Law of the Codification Commission of the Republic of Poland – Selected Issues The paper presents the course of the discussion of Edmund Krzymuski’s essay on crimes against life and health, which took place as part of the Section of Substantive Criminal Law of the Codification Commission of the Republic of Poland in June 24–27, 1920. The article focuses on the main threads of the referent’s questionnaire and is devoted i.a., to the crimes of murder, bodily harm, incitement to suicide, or the killing of a fetus. The work highlights both Krzymuski’s proposals, as well as different concepts supported by other members of the Section, which were included in the draft criminal code of 1932. That discussion was significant because most of these solutions are still in force today in the Polish legal system. The article also attempts to answer whether the circumstances related to the referent’s proposals could have influenced his decision to resign from further work within the Substantive Criminal Law Section of the Codification Commission of the Republic of Poland.

In this research, we developed boron-rich nanoparticles that can be used for boron neutron capture therapy as potential carriers for boron delivery to cancerous tissues. Functionalized carbonated boron nitride nanostructures (CBNs) were successfully synthesized in self-propagating combustion waves in mixtures of high-nitrogen explosives and boron compounds. The products’ composition, morphology, and structural features were investigated using Fourier transform infrared spectroscopy, powder X-ray diffraction, low-temperature nitrogen sorption analysis, thermogravimetric analysis, high-resolution scanning electron microscopy, and high-resolution transmission electron microscopy. The extreme conditions prevailing in combustion waves favor the formation of nanosized CBN hollow grains with highly disordered structures that are properly functionalized on the surface and inside the particles. Therefore, they are characterized by high porosity and good dispersibility in water, which are necessary for medical applications. During biological tests, a concentration-dependent effect of the obtained boron nitride preparations on the viability of normal and neoplastic cells was demonstrated. Moreover, the assessment of the degree of binding of fluorescently labeled nanoparticles to selected cells confirmed the relationships between the cell types and the concentration of the preparation at different incubation time points.

In the swiftly advancing field of swarm robotics and unmanned aerial vehicles, precise and effective testing methods are essential. This article explores the crucial role of software-in-the-loop (SITL) simulations in developing, testing, and validating drone swarm control algorithms. Such simulations play a crucial role in reproducing real-world operational scenarios. Additionally, they can (regardless of the type of application) accelerate the development process, reduce operational risks, and ensure the consistent performance of drone swarms. Our study demonstrates that different geometrical arrangements of drone swarms require flexible control strategies. The leader-based control model facilitates coherent movement and enhanced coordination. Addressing various issues such as communication delays and inaccuracies in positioning is essential here. These shortcomings underscore the value of improved approaches to collision avoidance. The research described in this article focused on the dynamics of drone swarms in a simulated context and emphasized their operational efficiency and adaptability in various scenarios. Advanced simulation tools were utilized to analyze the interaction, communication, and adaptability of autonomous units. The presented results indicate that the arrangement of drones significantly affects their coordination and collision avoidance capabilities. They also underscore the importance of control systems that can adapt to various situations. The impact of communication delays and errors in positioning systems on the required distance between drones in a grid structure is also presented. This article assesses the impact of different levels of GPS accuracy and communication delays on the coordination of group movement and collision avoidance capabilities.

Background: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disorder of the central nervous system characterized by autoimmune-mediated damage to oligodendrocytes and subsequent myelin destruction. Clinical implications: Clinically, the disease presents with many symptoms, often evolving over time. The insidious onset of MS often manifests with non-specific symptoms (prodromal phase), which may precede a clinical diagnosis by several years. Among them, headache is a prominent early indicator, affecting a significant number of MS patients (50–60%). Results: Headache manifests as migraine or tension-type headache with a clear female predilection (female-male ratio 2-3:1). Additionally, some disease-modifying therapies in MS can also induce headache. For instance, teriflunomide, interferons, ponesimod, alemtuzumab and cladribine are associated with an increased incidence of headache. Conclusions: The present review analyzed the literature data on the relationship between headache and MS to provide clinicians with valuable insights for optimized patient management and the therapeutic decision-making process.

Despite its significant growth over the past fifteen years, research on parental burnout is just beginning to explore the relationships of the syndrome with child behavior. Previous research with adolescents has shown the existence of associations between parental burnout and internalizing and externalizing behaviors in the offspring. The current study is an attempt to (i) replicate this preliminary evidence specifically among Chilean preschool children and (ii) explore the mediating/moderating effects of positive parenting that may be involved in these putative associations. A sample of 383 Chilean mothers participated in this cross-sectional online study. The results confirmed the associations between parental burnout and child internalizing and externalizing behaviors. We also observed that positive parenting was a mediator in the relationship linking parental burnout and the child’s internalizing (full mediation) and externalizing (partial mediation) behaviors. Positive parenting also partially mediated the association between the child’s externalizing behavior and parental burnout. Our results further suggested that the child’s externalizing behavior was possibly a more substantial contributing factor to parental burnout than the child’s internalizing behavior.