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Introduction: Ozempic is a new generation antihyperglycemic drug used to treat type 2 diabetes in adults whose underlying disease is not sufficiently controlled with physical activity and diet, as well as for long-term weight control in people with excess body weight and comorbidities. The aim of this study is to explore and integrate the latest literature on the analysis of the pharmacology, mechanism of action and clinical applications of Ozempic. Material and Methods of Research: A literature review focused on keywords related to the topic was performed using databases such as PubMed and Google Scholar. Results: Ozempic effectively lowers blood glucose levels and supports weight loss in patients with type 2 diabetes and obesity. Clinical trials have demonstrated its superiority over other antidiabetic medications, with significant reductions in HbA1c and body weight. Patients receiving Ozempic experienced improved glycemic control and cardiovascular outcomes, with manageable side effects. Ongoing research suggests additional benefits in cardiovascular prevention and obesity management. Conclusion: Ozempic (semaglutide) is a potent GLP-1 receptor agonist that effectively improves glycemic control and aids in weight reduction for patients with type 2 diabetes and obesity. Its practical administration, patient education, and regular monitoring are essential for optimal outcomes. Ongoing research and technological advancements, including the development of oral forms, promise to expand its applications and improve patient adherence, making Ozempic a versatile and valuable therapeutic option.

Introduction: Sodium-glucose cotransporter-2 inhibitors (SGLT2 inhibitors), known as flozins, are a recent class of medications gaining recognition for their effectiveness in diabetes, cardiovascular health, and heart failure management. The objective of this study is to examine and integrate recent literature concerning the mechanisms, effectiveness, and safety of SGLT2 inhibitors in managing heart failure. Material and Methods of Research: A literature review focused on keywords related to the topic was performed using databases such as PubMed and Google Scholar. Results: SGLT-2 inhibitors, initially developed for type 2 diabetes, significantly benefit heart failure (HF) with reduced, mildly reduced, and preserved ejection fractions by improving various cardiac outcomes. These drugs lower glucose levels and promote osmotic diuresis, natriuresis, and favorable metabolic effects, reducing cardiac preload and afterload. Consequently, SGLT-2 inhibitors are now pivotal in HF treatment, enhancing cardiac efficiency and reducing HF-related hospitalizations and mortality. Conclusion: SGLT-2 inhibitors substantially decrease cardiovascular risk and hospitalizations for heart failure in patients with or without type 2 diabetes, making them crucial in HF management. Consequently, SGLT-2 inhibitors should be considered first-line therapy for heart failure, regardless of concurrent medications, due to their efficacy and comprehensive benefits in managing this condition.

Introduction. Childhood infectious diseases have been a significant medical problem, with a global increase in recent years. Modern diagnostic methods and new vaccinations are available. Poland is part of the WHO-coordinated global measles and rubella elimination program. Controversy surrounds mandatory and recommended vaccinations in Poland. There has been a concerning increase in the abandonment of vaccinating children, leading to a resurgence of infectious diseases. In 2024, the WHO reported a significant increase in measles cases in the European region, including in Poland. It's crucial to remind people of these diseases and warn them about the complications they bring. Aim of study. The aim of this study is to investigate the increasing occurrence of infectious diseases in childhood and examine the correlation with declining vaccination rates across society. Materials and methods. An unsystematic review of scientific literature was conducted, employing specific keywords such as „measles,” „pertussis,” „rubella,” „infectious diseases,” „vaccination,” and „hib.” The review was executed on the PubMed database, analyzing a total of 59 sources published until the conclusion of 2024. Conclusions. To control and eliminate infectious diseases, it is vital to maintain and improve vaccination rates. Policymakers and healthcare providers should prioritize immunization programs and address barriers to vaccine access. Further research is crucial to develop comprehensive strategies for increasing vaccination coverage and understanding vaccine-preventable diseases in modern public health challenges.

This article examines medieval Monstrous Races in the Psalter World Map from the thirteenth-century English Map Psalter (British Library, Add. MS 28681). It suggests the map’s reading as a pictorial expression of liminality situated in a to- and fro-ing between conceptions of Us/the Self and Them/the Other. I consider how the map exiles the Monstrous Races through spatially articulated geographical distance; inserts Them into notions of Us via inclusion in God’s salvation plan; and gestures towards a category crisis in the Us-Them divide by celebrating England’s own peripheral placement on the mappa mundi’s border. The border-space which constitutes the nexus of my investigation extends to encompass the Psalter World Map’s materiality and the self-definition by means of difference enacted by the reader-viewer in corporeal terms.

This article addresses the issue of public support for the development of renewable energy and the assessment of this support from the perspective of farmers in Eastern Poland. Since it is a region characterized by a relatively high share of agriculture in the economy, a diversified structure of this sector, and at the same time, a region with a relatively high level of energy poverty, it can be considered a good example for illustrating the research problem. To achieve the goal, surveys were carried out covering 519 farms. Upon the consideration of a literature review and the research results of other authors, the collected opinions of the owners of these farms regarding the motivators encouraging them to invest in renewable energy technologies and the assessment of the role of the state in supporting energy transformation allowed for the formulation of conclusions. The research results indicate that renewable energy technologies are present in 47% of the surveyed farms, while in 36% of them, investments were financed from farmers’ own funds. This means that the possibility of obtaining support from public funds is not a necessary condition for implementing renewable energy investments.

Abstract Background Haematopoiesis is a process of formation of mature blood cells from hematopoietic progenitors in bone marrow. Haematopoietic progenitors are stimulated by growth factors and cytokines to proliferate and differentiate, and they die via apoptosis when these factors are depleted. An aberrant response to growth environment may lead to haematological disorders. Bomapin (serpinb10) is a hematopoietic- and myeloid leukaemia-specific protease inhibitor with unknown function. Results We found that the majority of naturally expressed bomapin was located in the nucleus. Both the natural and recombinant bomapin had a disulfide bond which linked the only two bomapin cysteines: one located in the CD-loop and the other near the C-terminus. Computer modelling showed that the cysteines are distant in the reduced bomapin, but can easily be disulfide-linked without distortion of the overall bomapin structure. Low-level ectopic expression of bomapin in bomapin-deficient K562 cells resulted in about 90% increased cell proliferation under normal growth conditions. On the other hand, antisense-downregulation of natural bomapin in U937 cells resulted in a decreased cell proliferation. Bomapin C395S mutant, representing the reduced form of the serpin, had no effect on cell proliferation, suggesting that the disulfide bond-linked conformation of bomapin is biologically important. The bomapin-dependent effect was specific for myeloid cells, since ectopic expression of the serpin in HT1080 cells did not change cell proliferation. In contrast to the survival-promoting activity of bomapin in cells cultured under optimal growth conditions, bomapin enhanced cell apoptosis following growth factor withdrawal. Conclusions We propose that bomapin is a redox-sensitive nuclear serpin that augments proliferation or apoptosis of leukaemia cells, depending on growth factors availability.

Abstract Selection of livestock has not only led to changes in the level of their performance but also modified their behavior. As a result, within a single species, we have to deal with different behaviors of different breeds. In our study, we assumed that the different behaviors within a species are due to differences in the morphology and physiology of behavior-related systems. Two breeds of hens were used as a model: the highly reactive, fearful and high-performance Leghorn breed and proactive, unselected Green-legged Partridge breed. The higher reactivity and fearfulness of Leghorn hens in comparison to the Green-legged Partridge breed may be related to the greater number of neurons in the paraventricular nucleus and anterior hypothalamus and the higher content of zinc and iron in the brain, as these elements are involved in neuronal conduction and myelination processes. The reactive behaviours of Green-legged Partridge hens may be associated with the lower number of neurons in the paraventricular nucleus and the anterior hypothalamus and the higher concentration of dopamine and copper ions in the brain. The analyses confirmed the hypothesis of the existence of interbreed differences in the morphology and physiology of behaviour-related systems, which most probably emerged through unintentional and correlated selection towards high production performance. Consequently, attention should be drawn that the selection of a given genotype (breed) towards a specific environment could lead to creation of highly specialised lines that may not achieve homeostasis in every maintenance system.

Abstract Background Neuromedin U (NMU) was identified as one of the hub genes closely related to colorectal cancer (CRC) progression and was recently shown to be a motility inducer in CRC cells. Its autocrine signalling through specific receptors increases cancer cell migration and invasiveness. Because of insufficient knowledge concerning NMU accessibility and action in the tumour microenvironment, its role in CRC remains poorly understood and its potential as a therapeutic target is still difficult to define. Methods NMU expression in CRC tissue was detected by IHC. Data from The Cancer Genome Atlas were used to analyse gene expression in CRC. mRNA and protein expression was detected by real-time PCR, immunoblotting or immunofluorescence staining and analysed using confocal microscopy or flow cytometry. Proteome Profiler was used to detect changes in the profiles of cytokines released by cells constituting tumour microenvironment after NMU treatment. NMU receptor activity was monitored by detecting ERK1/2 activation. Transwell cell migration, wound healing assay and microtube formation assay were used to evaluate the effects of NMU on the migration of cancer cells, human macrophages and endothelial cells. Results Our current study showed increased NMU levels in human CRC when compared to normal adjacent tissue. We detected a correlation between high NMUR1 expression and shorter overall survival of patients with CRC. We identified NMUR1 expression on macrophages, endothelial cells, platelets, and NMUR1 presence in platelet microparticles. We confirmed ERK1/2 activation by treatment of macrophages and endothelial cells with NMU, which induced pro-metastatic phenotypes of analysed cells and changed their secretome. Finally, we showed that NMU-stimulated macrophages increased the migratory potential of CRC cells. Conclusions We propose that NMU is involved in the modulation and promotion of the pro-metastatic tumour microenvironment in CRC through the activation of cancer cells and other tumour niche cells, macrophages and endothelial cells. Video abstract

Abstract Background Successful colorectal cancer (CRC) therapy often depends on the accurate identification of primary tumours with invasive potential. There is still a lack of identified pathological factors associated with disease recurrence that could help in making treatment decisions. Neuromedin U (NMU) is a secretory neuropeptide that was first isolated from the porcine spinal cord, and it has emerged as a novel factor involved in the tumorigenesis and/or metastasis of many types of cancers. Previously associated with processes leading to CRC cell invasiveness, NMU has the potential to be a marker of poor outcome, but it has not been extensively studied in CRC. Methods Data from The Cancer Genome Atlas (TCGA) were used to analyse NMU and NMU receptor (NMUR1 and NMUR2) expression in CRC tissues vs. normal tissues, and real-time PCR was used for NMU and NMU receptor expression analysis. NMU protein detection was performed by immunoblotting. Secreted NMU was immunoprecipitated from cell culture-conditioned media and analysed by immunoblotting and protein sequencing. DNA demethylation by 5-aza-CdR was used to analyse the regulation of NMUR1 and NMUR2 expression. NMU receptor activity was monitored by detecting calcium mobilisation in cells loaded with fluo-4, and ERK1/2 kinase activation was detected after treatment with NMU or receptor agonist. Cell migration and invasion were investigated using membrane filters. Integrin expression was evaluated by flow cytometry. Results The obtained data revealed elevated expression of NMU and NMUR2 in CRC tissue samples and variable expression in the analysed CRC cell lines. We have shown, for the first time, that NMUR2 activation induces signalling in CRC cells and that NMU increases the motility and invasiveness of NMUR2-positive CRC cells and increases prometastatic integrin receptor subunit expression. Conclusions Our results show the ability of CRC cells to respond to NMU via activation of the NMUR2 receptor, which ultimately leads to a shift in the CRC phenotype towards a more invasive phenotype.

Postmortem carbon monoxide (CO) and hydrogen cyanide (HCN) diffusion under ambient conditions was assessed in a human cadaver model. The main objective of this study was to determine whether the postmortem diffusion of HCN and CO greatly affected the determination of HCN, carboxyhemoglobin (COHb), and carboxymyoglobin (COMb). Layered samples of blood, musculocutaneous, and muscular specimens were collected from the adult cadavers and placed in the tight chambers designed for the purpose of this experiment. The specimens were treated with CO and HCN for 24 h. COHb and COMb were determined using headspace gas chromatography (GC) with an O-FID detector while the HCN values were assessed using a GC headspace with an NPD detector. It was shown that the skin substantially limited the diffusion of CO which penetrated the superficial layers of the muscle very slightly, all the while not affecting the blood level of COHb in the 4.5 cm layer of the muscle located underneath. There were no differences regarding the CO diffusion between superficially charred and thermally coagulated compared to that observed in intact integuments. In addition, the cutaneous sample deprived of the adipose layer was not shown to be a barrier to the moderate diffusion of CO into the blood layer below. HCN was found to easily diffuse from the skin to the blood vessels (vein specimens), and partial charring and thermocoagulation of the superficial muscular layer favored the diffusion of cyanides into the tissues. Similarly to CO, HCN diffusion to the blood and muscles was greatly limited by the adipose layer.

The aim of the research paper was to present a character description of organic agriculturalholdings and identify factors affecting profitability of these holdings basing on the opinions of farmersspecializing in such production. The area analyzed in this research was the Podlaskie Voivodeship. Inorder to achieve the aim, various research methods were employed, such as the study of relevant literatureopinion surveys conducted using a questionnaire directed to 101 organic farms (selected randomlyensuring representativeness of results) as well as means of descriptive statistics. The conducted researchindicates that a typical organic farmer in the Podlaskie Voivodeship is 48 years old and has 16 years ofexperience in agricultural holding management. He is also well educated (44% have higher education)and possesses good knowledge about organic agriculture. Almost 80% of analyzed agricultural holdingshave certificates, usually for several products. 51% produce mostly for their own needs, while productionof only every third is for the most part dedicated to market purposes. In 55% of these holdings, productionis oriented mostly towards plant production, whereas 35% is multidirectional. In the majority of farmers’opinions, the economic situation of their holdings is comparable to that of conventional farms. Only everyfifth farmer considers their situation to better. According to the respondents, subsidies from the EuropeanUnion are among the most important factors determining profitability of organic agricultural production.The factors that affect profitability negatively, according to interviewed farmers, are: low sale prices,unfavorable climate conditions, high costs of obtaining certificates and overly extensive bureaucracy

Hemp seed (Cannabis sativa L.) contain large amounts of nutrients, e.g. protein, dietary fiber, minerals, and unsaturated fatty acids, which make them a good fortifying component in food production. The aim of the present study was to determine the effect of hemp addition on the physicochemical properties, cooking quality, texture parameters and sensory properties of durum wheat pasta. The samples were fortified with 5-40% of commercially available hemp flour or 2.5-10% of hemp cake obtained from hemp seed oil pressing. Our study showed that the addition of hemp seed raw materials led to an increase in the protein, total dietary fiber (TDF), ash and fat content in the pasta samples. Due to its lower granulation and higher nutritional value, hemp flour was found to be a better raw material for the fortification of pasta than hemp cake. Pasta enriched with hemp flour at the level of 30-40% contains 19.53-28.87% d.m. of protein and 17.02-21.49% d.m. of TDF and according to the EU, a definition can be described as a high-protein and high-fiber products. All enriched pasta samples were also characterized by safe Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) content, and their sensory properties were accepted by consumers.

The routine techniques currently applied for the determination of nicotine and its major metabolites, cotinine, and trans-3′-hydroxycotinine, in biological fluids, include spectrophotometric, immunoassays, and chromatographic techniques. The aim of this study was to develop, and compare two new chromatographic methods high-performance liquid chromatography coupled to triple quadrupole mass spectrometry (HPLC-QQQ-MS/MS), and RP-HPLC enriched with chaotropic additives, which would allow reliable confirmation of tobacco smoke exposure in toxicological and epidemiological studies. The concentrations of analytes were determined in human plasma as the sample matrix. The methods were compared in terms of the linearity, accuracy, repeatability, detection and quantification limits (LOD and LOQ), and recovery. The obtained validation parameters met the ICH requirements for both proposed procedures. However, the limits of detection (LOD) were much better for HPLC-QQQ-MS/MS (0.07 ng mL−1 for trans-3′-hydroxcotinine; 0.02 ng mL−1 for cotinine; 0.04 ng mL−1 for nicotine) in comparison to the RP-HPLC-DAD enriched with chaotropic additives (1.47 ng mL−1 for trans-3′-hydroxcotinine; 1.59 ng mL−1 for cotinine; 1.50 ng mL−1 for nicotine). The extraction efficiency (%) was concentration-dependent and ranged between 96.66% and 99.39% for RP-HPLC-DAD and 76.8% to 96.4% for HPLC-QQQ-MS/MS. The usefulness of the elaborated analytical methods was checked on the example of the analysis of a blood sample taken from a tobacco smoker. The nicotine, cotinine, and trans-3′-hydroxycotinine contents in the smoker’s plasma quantified by the RP-HPLC-DAD method differed from the values measured by the HPLC-QQQ-MS/MS. However, the relative errors of measurements were smaller than 10% (6.80%, 6.72%, 2.04% respectively).

Celem artykułu jest prezentacja wyników badania związku osobowości zawodowej z zadowoleniem z pracy w centrach usług księgowych. Zgodnie z teorią J.L. Hollanda niedopasowanie osobowości zawodowej do środowiska pracy powoduje niezadowolenie z pracy. Środowisko pracy w centrum usług księgowych ma charakter konwencjonalny. W celu odpowiedzi na pytanie badawcze, czy osobowość zawodowa ma związek z zadowoleniem z pracy w centrum usług księgowych najpierw zbadano osobowość zawodową 23 pra- cowników takiego centrum z Łodzi. Następnie spośród badanych wybrano cztery osoby (dwie o konwen- cjonalnym typie osobowości zawodowej i dwie niekonwencjonalne) i przeprowadzono z nimi wywiady, w których pytano o satysfakcję z wykonywanej pracy. W przypadku trzech spośród tych czterech osób okazało się, że dopasowanie osobowości zawodowej i środowiska pracy ma związek z zadowoleniem z pracy. Badanie zaprezentowane w artykule ma charakter nowatorski.

The aim of this paper was to analyze reasons and a range of changes in agricultural land areas due to allocation them for non-agricultural purposes across a period of 1990-2015 in Poland. This phenomena has not been sufficiently considered till now. Lack of this knowledge does not allow effective reduction of the decline of agricultural land by appropriate legislation and administrative action, especially on urban areas. In Poland, a significant proportion of agricultural land is allocated annually for non-agricultural purposes, which is connected with their permanent withdrawal from agricultural production. The permanent decline in the area of agricultural land in the country has been observed since the beginning of the systemic transformation. The dominant direction of the land withdrawal for non-agricultural purposes is their allocation to housing construction. In 1995 the Law on the protection of agricultural and forest land was introduced. This law includes strengthened economic tools for the protection of agricultural land in the form of mandatory charges for the withdrawal of agricultural land showing the best soil quality. This has led to a significant reduction in agricultural land use withdrawal. However, accelerated regional development following the accession of Poland to the EU and, then, the need to expand technical infrastructure resulted in several amendments to the 1995 Act, significantly weakened the protection of agricultural and forest land. It seems that the land as the unrepeatable good should be strictly covered by more respect and protection than ever before, especially in areas with the highest production value.

Background: Identification and quantitative determination of cytisine, especially in biological samples and pharmaceutical formulations, is still a difficult analytical task. Cytisine is an alkaloid with a small and very polar molecule. For this reason, it is very weakly retained on reversed phase (RP) stationary phases, such as commonly used alkyl-bonded phases. The very weak retention of cytisine causes it to be eluted together with the components of biological matrices. Objective: Comparison and evaluation of various chromatographic systems for analysis of cytisine in different matrices—serum, saliva and pharmaceutical formulation—by high performance liquid chromatography (HPLC) with diode array (DAD), fluorescence (FLD) and mass spectrometry (MS) detection. Methods: The analyses were performed using HPLC in reversed phase (RP), hydrophilic interaction liquid chromatography (HILIC) and ion exchange chromatography (IEC) modes. Different sample pre-treatment methods were tested: Protein precipitation (with acetone, methanol (MeOH) or acetonitrile (ACN), and solid phase extraction (SPE) using cartridges with octadecyl (C18), hydrophilic-lipophilic balanced copolymer (HLB) or strong cation exchange sorbents (Strata X-C). Conclusion: Significant differences were observed in retention parameters with a change of the used chromatographic system. The various properties of stationary phases resulted in differences in analyte retention, peaks’ shape and systems’ efficiency. The weakest retention was observed using RP systems; however, the use of the Polar RP phase can be an alternative for application in green chromatography. In the strongest retention was observed using a strong cation exchange (SCX) phase. The most optimal systems were chosen for the analysis of cytisine in the pharmaceutical preparation, serum and saliva after sample pre-treatment with the new SPE procedure. Due to the sensitivity, the use of HPLC-DAD or HPLC-FLD is the most optimal for drug analysis in pharmaceutical preparations, whereas HPLC-MS is suitable for analysis of cytisine in biological samples.

The dysfunction of oligodendrocytes (OLs) is regarded as one of the major causes of inefficient remyelination in multiple sclerosis, resulting gradually in disease progression. Oligodendrocytes are derived from oligodendrocyte progenitor cells (OPCs), which populate the adult central nervous system, but their physiological capability to myelin synthesis is limited. The low intake of essential lipids for sphingomyelin synthesis in the human diet may account for increased demyelination and the reduced efficiency of the remyelination process. In our study on lipid profiling in an experimental autoimmune encephalomyelitis brain, we revealed that during acute inflammation, nervonic acid synthesis is silenced, which is the effect of shifting the lipid metabolism pathway of common substrates into proinflammatory arachidonic acid production. In the experiments on the human model of maturating oligodendrocyte precursor cells (hOPCs) in vitro, we demonstrated that fish oil mixture (FOM) affected the function of hOPCs, resulting in the improved synthesis of myelin basic protein, myelin oligodendrocyte glycoprotein, and proteolipid protein, as well as sphingomyelin. Additionally, FOM reduces proinflammatory cytokines and chemokines, and enhances fibroblast growth factor 2 (FGF2) and vascular endothelial growth factor (VEGF) synthesis by hOPCs was also demonstrated. Based on these observations, we propose that the intake of FOM rich in the nervonic acid ester may improve OL function, affecting OPC maturation and limiting inflammation.

Depresja jest najczęstszym schorzeniem psychicznym występującymu pacjentów tzw. podstawowej opieki zdrowotnej i stwierdzasię ją u 12,5% chorych, a w przebiegu schorzeń przewlekłych jestroz poznawana wielokrotnie częściej.Do rozwoju depresji w przebiegu schorzeń przewlekłych przyczyniasię wiele czynników, takich jak: predyspozycje genetyczne, predyspozycjepsychiczne, długotrwale utrzymujący się stres orazzwiększenie stężeń cytokin prozapalnych w ośrodkowym układzienerwowym. Ośrodkowy układ nerwowy w wyniku działania cytokinprozapalnych aktywuje wiele zmian w układzie neuroendokrynnymi immunologicznym, określanych jako „zachowanie chorobowe” (sickness behaviour).W reumatoidalnym zapaleniu stawów (RZS) depresja występujeu 13–65% chorych, ale tylko u 25% chorych jest rozpoznana. Tak częstewystępowanie depresji jest wynikiem utrzymywania się dużegostężenia cytokin prozapalnych wtym schorzeniu, powodującego zaburzeniaw zachowaniu. Depresja wpływa negatywnie na przebieg RZS,nasilając objawy somatyczne choroby. Z kolei wyniki leczenia depresjisą tym gorsze, im większa jest aktywność RZS, co powoduje zmniejszenieskuteczności leczenia podtrzymującego i zwiększa możliwośćwy stąpienia nawrotów depresji po pierwszym epizodzie. Udowadniato konieczność jednoczesnego intensywnego leczenia obu chorób i ichwczesnego rozpoznania. Rozpoznanie depresji może nastręczać dużotrudności z powodu nakładania się objawów wy stępujących zarównow depresji, jak i w RZS, takich jak: zmęczenie, brak apetytu, zmniejszeniemasy ciała, różnego typu dolegliwości bólowe itp. Nierozpoznanadepresja w przebiegu RZS, poza wpływem na nasilenie objawówchoroby, zmniejsza skuteczność stosowanej terapii, z uwagi na gorsząwspółpracę pacjenta i mniejsze zaangażowanie w leczenie. Zwiększato ryzyko myśli i prób samobójczych oraz skraca czas przeżycia pacjentówchorych na RZS.

This study tested the hypothesis that Mycobacterium tuberculosis (Mtb) uses a cholesterol oxidase enzyme (ChoD) to suppress a toll-like receptor type 2- (TLR2-) dependent signalling pathway to modulate macrophages’ immune response. We investigated the impact of Mtb possessing or lacking ChoD as well as TBChoD recombinant protein obtained from Mtb on the expression and activation of two key intracellular proteins involved in TLR2 signalling in human macrophages. Finally, the involvement of TLR2-related signalling proteins in an inflammatory/immunosuppressive response of macrophages to Mtb was evaluated. We demonstrate that wild-type Mtb but not the ∆choD mutant decreased the cytosolic IRAK4 and TRAF6 protein levels while strongly enhancing IRAK4 and TRAF6 mRNA levels in macrophages. Our data show that the TLR2 present on the surface of macrophages are involved in disturbing the signalling pathway by wild-type Mtb. Moreover, recombinant TBChoD effectively decreased the cytosolic level of TRAF6 and lowered the phosphorylation of IRAK4, which strongly confirm an involvement of cholesterol oxidase in affecting the TLR2-related pathway by Mtb. Wild-type Mtb induced an immunosuppressive response of macrophages in an IRAK4- and TRAF6-dependent manner as measured by interleukin 10 production. In conclusion, ChoD is a virulence factor that enables Mtb to disturb the TLR2-related signalling pathway in macrophages and modulate their response.

The transcription factor Snail triggers epithelial-to-mesenchymal transition (EMT), endowing cancer cells with invasive properties during tumor progression. Extracellular vesicles (EVs) released from cancer cells at various stages of cancer progression are known to influence the tumor pre-metastatic niche and metastatic potential. The aim of this study was to analyze the effect of Snail on murine colon adenocarcinoma cells (MC38 line) and on the characteristics of their EVs. Stable clones of Snail-overexpressing MC38 cells were investigated in vitro versus Mock cells. Increased expression of matrix metalloproteinase MMP-14 and augmented activity of MMP-9 and -14 were observed in Snail-MC38 cells. There was no change in the transcriptomic profile of proteoglycans in Snail-MC38 cells; however, the protein level of Glypican-1 (GPC1) was enhanced in EVs released from those cells. Our finding that GPC1 protein level was enhanced in EVs released from MC38 cells that overexpressed Snail and were in an early EMT stage might explain the specificity of the GPC1 biomarker in colon cancer diagnosis. Further, our data suggest that Snail, by changing the level of GPC1 on EVs released by colon cancer cells, may affect the generation of a distant premetastatic niche and metastatic organotropism in colon adenocarcinoma.

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune neuroinflammatory disease. In contrast to multiple sclerosis, autoantibodies against aquaporin-4 (AQP4) expressed on astrocytic end-feet have been exclusively detected in sera of NMOSD patients. Several lines of evidence suggested that anti-AQP4 autoantibodies are pathogenic, but the mechanism triggering inflammation, impairment of astrocyte function, and the role of neutrophils presented in NMOSD cerebrospinal fluid remains unknown. In this study, we tested how human neutrophils affect astrocytes in the presence of anti-AQP4 Ab-positive serum derived from NMOSD patients. An in vitro model of inflammation consisted of human astrocyte line, NMOSD serum, and allogenic peripheral blood neutrophils from healthy individuals. We showed evidence of pathogenicity of NMOSD serum, which by consecutive action of anti-AQP4 Abs, complement system, and neutrophils affected astrocyte function. Anti-AQP4 Ab binding astrocytes initiated two parallel complementary reactions. The first one was dependent on the complement cytotoxicity via C5b-9 complex formation, and the second one on the reverse of astrocyte glutamate pump into extracellular space by C5a-preactivated neutrophils. As a consequence, astrocytes were partially destroyed; however, a major population of astrocytes polarized into proinflammatory cells which were characterized by pathological glutamate removal from extracellular space.

In this study, the relationship between the inhibitory effects of extracts from rye-buckwheat ginger cakes supplemented with low and high rutin dosage baked without or with dough fermentation step on the formation of fluorescent advanced glycation end-products (AGEs), and phenolic compounds, rutin, D-chiro-inositol and antioxidant capacity were addressed. The cakes were based on rye flour substituted by light buckwheat flour or flour from roasted buckwheat groats at 30% level, and were produced with or without dough fermentation step. The inhibitory effect against AGEs formation was studied in bovine serum albumin (BSA)-glucose and BSA-methylglyoxal (MGO) systems. The antioxidant capacity was measured by 2,2-diphenyl- -1-picrylhydrazyl (DPPH) and cyclic voltammetry (CV), rutin and D-chiro-inositol contents by HPLC and total phenolics (TPC) by spectrophotometric assays. The study showed the inhibitory effects of extracts from rye-buckwheat ginger cakes supplemented with low and high rutin dosage. The results of the inhibitory activity were highly correlated in two applied model systems. Enrichment of rye-buckwheat ginger cakes with rutin improved their antioxidant properties. The correlation studies showed that the inhibitory effects of rye-buckwheat ginger cakes produced with dough fermentation step and enhanced with rutin against formation of AGEs were highly correlated with TPC, rutin and D-chiro-inositol contents, and antioxidant capacity. Moreover, the effect of rutin enrichment was clearly seen in cakes obtained with dough fermentation step, even the inhibitory activity was slightly lower as compared to the cakes produced without dough fermentation.

Lumican, a small leucine rich proteoglycan, inhibits MMP-14 activity and melanoma cell migration in vitro and in vivo. Snail triggers epithelial-mesenchymal transitions endowing epithelial cells with migratory and invasive properties during tumor progression. The aim of this work was to investigate lumican effects on MMP-14 activity and migration of Snail overexpressing B16F1 (Snail-B16F1) melanoma cells and HT-29 colon adenocarcinoma cells. Lumican inhibits the Snail induced MMP-14 activity in B16F1 but not in HT-29 cells. In Snail-B16F1 cells, lumican inhibits migration, growth, and melanoma primary tumor development. A lumican-based strategy targeting Snail-induced MMP-14 activity might be useful for melanoma treatment.

Wstęp i cel pracy: Zesztywniające zapalenie stawów kręgosłupa(ZZSK) to przewlekła, zapalna choroba, dotycząca głównie młodychmężczyzn, prowadząca do zupełnego usztywnienia kręgosłupa,a często zajmująca także stawy obwodowe, układ sercowo--naczyniowy i błonę naczyniową oka. Stosowanie blokerów TNFznacznie poprawia funkcję i jakość życia tych chorych. Celem pracybyła ocena skuteczności i bezpieczeństwa leczenia etanerceptemprzez 12 miesięcy 6 mężczyzn chorych na ZZSK. Materiał i metody: Badaniem objęto 6 mężczyzn chorych na ZZSK(średni wiek 35,7 roku, w zaawansowanym okresie choroby: sacroiliitisokres III/IV, spondylitis okres III, średni czas trwania choroby11,3 roku – tab. I). Badano ruchomość kręgosłupa, rozszerzalnośćklatki piersiowej, liczbę stawów bolesnych i obrzękniętych. Aktywnośćchoroby oceniano za pomocą skali VAS (ból i aktywność choroby),indeksów BASDAI i BASFI. Stopień niepełnosprawności ocenianoza pomocą kwestionariusza HAQ. Oceniano laboratoryjneparametry stanu zapalnego: OB, CRP. Wymienione parametry ocenianoco 3 miesiące (ryc. 1 i 2). Uprzednio stosowane leczenieprzedstawiono w tabeli II. Wyniki: Wszystkie badane parametry uległy znamiennej poprawiew trakcie prowadzonej obserwacji (tab. III, IV i V). Znamiennie zmniejszyło się także stężenie CRP w badanych surowicach. Podczasobserwacji nie było zdarzeń niepożądanych. Wnioski: Mała liczebność grupy pozwala na wyciągnięcie wstępnychwniosków. Należy podkreślić, że u wszystkich chorych stosowaneleczenie skróciło czas trwania sztywności porannej i nasileniebólu, czego nie uzyskano po wieloletnim leczeniu standardowym.Roczne leczenie etanerceptem było dobrze tolerowane przez chorychi nie obserwowano zdarzeń niepożądanych.

This paper has two aims. First, we investigate how often people make choices conforming to Bayes’ rule when natural sampling is applied. Second, we show that using Bayes’ rule is not necessary to make choices satisfying Bayes’ rule. Simpler methods, even fallacious heuristics, might prescribe correct choices reasonably often under specific circumstances. We considered elementary situations with binary sets of hypotheses and data. We adopted an ecological approach and prepared two-stage computer tasks resembling natural sampling. Probabilistic relations were to be inferred from a set of pictures, followed by a choice between the data which was made to maximize a chance for a preferred outcome. Using Bayes’ rule was deduced indirectly from choices.Study 1 (N=60) followed a 2 (gender: female vs. male) x 2 (education: humanities vs. pure sciences) between-subjects factorial design with balanced cells, and a number of correct choices as a dependent variable. Choices satisfying Bayes’ rule were dominant. To investigate ways of making choices more directly, we replicated Study 1, adding a task with a verbal report. In Study 2 (N=76) choices conforming to Bayes’ rule dominated again. However, the verbal reports revealed use of a new, non-inverse rule, which always renders correct choices, but is easier than Bayes’ rule to apply. It does not require inversing conditions (transforming P(H) and P(D|H) into P(H|D)) when computing chances). Study 3 examined efficiency of the three fallacious heuristics (pre-Bayesian, representativeness, and evidence-only) in producing choices concordant with Bayes’ rule. Computer-simulated scenarios revealed that the heuristics produce correct choices reasonably often under specific base rates and likelihood ratios. Summing up we conclude that natural sampling leads to most choices conforming to Bayes’ rule. However, people tend to replace Bayes’ rule with simpler methods, and even use of fallacious heuristics may be satisfactorily efficient.

Background: Despite significant improvements in the conventional anti-ovarian cancer therapies, tumor cell resistance to various cytostatic drugs remains a relevant problem. Therefore, the new cancer treatment strategies are being developed. Among many agents that have been studied for their potential anti-cancer activity, the most promising are the nitric oxide (NO) donors-syntethic compounds that release NO in vivo and/or in vitro. Aim: We have evaluated the effect of NO donors on the SK-OV-3 and OVCAR-3 ovarian cancer cell lines. We assessed some of the cancer cells’ specific features: the uncontrolled proliferation, over-activation of particular signaling proteins, high resistance to therapeutics and elevated expression and secretion of invasiveness/metastatic factors. Methods: Two members of NONOates family were used: SPER/NO and DETA/NO. Cancer cell lines were cultured with different concentrations of NO donors. The cytotoxic, pro-apoptotic activity of NO donors and their impact on the phosphorylation status of STAT-3 and AKT in cells were determined. The expression of VEGF-A, MMPs and TGF-β was also evaluated. Results: NO donors inhibited ovarian cancer cells growth making them also more susceptible to the cisplatin cytotoxic activity. Moreover, both NO donors induced apoptosis of cells and decreased activity of signaling proteins (STAT3 and AKT). Similarly, SPER/NO and DETA/NO lowered the secretion of pro-metastatic factors, responsible for cancer cells invasiveness. Conclusions: The obtained results show that both NO donors demonstrated a wide range of action on both ovarian cancer cell lines. Therefore, they have a high potential of being a supporting compounds in the cancer therapies.

The effect of selected spices included in the recipe of rye-buckwheat cakes on sensory quality, nutritional value, and Maillard reaction (MR) products formation was addressed in this study. The cakes with cloves, nutmeg, allspice, cinnamon, vanilla, and spice mix addition revealed the highest overall quality values. Cakes enriched with cloves, allspice, and spice mix showed the highest rutin content and almost threefold higher available lysine contents whereas cakes enhanced with mix, cloves, and cinnamon were the richest source of phenolic compounds. The highest antioxidant capacity showed cakes with cloves and spice mix. The furosine, a marker of early stage of MR, was decreased in cakes with cloves, allspice, spice mix, and vanilla whereas fluorescent intermediatory compounds were reduced in cakes enhanced with cloves, allspice, and cinnamon. In contrast, browning index was increased as compared to cakes without spices. The FAST index was significantly lowered in all cakes enriched with spices, especially with cloves, allspice, and mix addition. The presence of cloves, allspice, and vanilla in cake formula was the most efficient in acrylamide strategy. It can be suggested that cloves, allspice, and vanilla might be used for production of safety and good quality cakes.

Ovarian cancer is one of the deadliest gynecological malignancies among women. The reason for this outcome is the frequent acquisition of cancer cell resistance to platinum-based drugs and unresponsiveness to standard therapy. It has been increasingly recognized that the ability of ovarian cancer cells to adopt more aggressive behavior (mainly through the epithelial-to-mesenchymal transition, EMT), as well as dedifferentiation into cancer stem cells, significantly affects drug resistance acquisition. Transcription factors in the Snail family have been implicated in ovarian cancer chemoresistance and metastasis. In this article, we summarize published data that reveal Snail proteins not only as key inducers of the EMT in ovarian cancer but also as crucial links between the acquisition of ovarian cancer stem properties and spheroid formation. These Snail-related characteristics significantly affect the ovarian cancer cell response to treatment and are related to the acquisition of chemoresistance., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

During metastasis, cancer cells undergo phenotype changes in the epithelial-mesenchymal transition (EMT) process. Extracellular vesicles (EVs) released by cancer cells are the mediators of intercellular communication and play a role in metastatic process. Knowledge of factors that influence the modifications of the pre-metastatic niche for the migrating carcinoma cells is important for prevention of metastasis. We focus here on how cancer progression is affected by EVs released from either epithelial-like HT29-cells or from cells that are in early EMT stage triggered by Snail transcription factor (HT29-Snail). We found that EVs released from HT29-Snail, as compared to HT29-pcDNA cells, have a different microRNA profile. We observed the presence of interstitial pneumonias in the lungs of mice injected with HT29-Snail cells and the percent of mice with lung inflammation was higher after injection of HT29-Snail-EVs. Incorporation of EVs released from HT29-pcDNA, but not released from HT29-Snail, leads to the increased secretion of IL-8 from macrophages. We conclude that Snail modifications of CRC cells towards more invasive phenotype also alter the microRNA cargo of released EVs. The content of cell-released EVs may serve as a biomarker that denotes the stage of CRC and EVs-specific microRNAs may be a target to prevent cancer progression.

Endothelial-mesenchymal transition (EndMT) is a crucial phenomenon in regulating the development of diseases, including cancer metastasis and fibrotic disorders. The primary regulators of disease development are zinc-finger transcription factors belonging to the Snail family. In this study, we characterized the myocardin-related transcription factor (MRTF)-dependent mechanisms of a human snail promoter regulation in TGF-β-stimulated human endothelial cells. Although in silico analysis revealed that the snail promoter's regulatory fragment contains one GCCG and two SP1 motifs that could be occupied by MRTFs, the genetic study confirmed that MRTF binds only to SP1 sites to promote snail expression. The more accurate studies revealed that MRTF-A binds to both SP1 elements, whereas MRTF-B to only one (SP1near). Although we found that each MRTF alone is capable of inducing snail expression, the direct cooperation of these proteins is required to reinforce snail expression and promote the late stages of EndMT within 48 hours. Furthermore, genetic and biochemical analysis revealed that MRTF-B alone could induce the late stage of EndMT. However, it requires a prolonged time. Therefore, we concluded that MRTFs might cause EndMT in a fast- and slow-dependent manner. Based on MRTF-dependent Snail upregulation, we recognized that TGF-β1, as an MRTF-B regulator, is involved in slow EndMT induction, whereas TGF-β2, which altered both MRTF-A and MRTF-B expression, promotes a fast EndMT process.