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In Central and Eastern Europe, wolf populations have been increasing over the last two decades, recolonizing areas from which the species had been previously exterminated. As wolves are still recovering after years of persecution by humans, recognizing pathogens infecting this species, including tick-borne infections, is crucial for its conservation. On the other hand the high mobility of wolves and their frequent contacts with humans, dogs, and other domestic species make them a potentially important zoonotic reservoir. In this paper, we used molecular methods to determine the prevalence of tick-borne pathogens in the following genera: Anaplasma, Babesia, Bartonella, Borrelia, and Rickettsia in 50 free-ranging wolves from Poland. We detected Babesia canis in the blood of nine individuals (prevalence 9/50=18 %). The obtained sequence showed the highest similarity to B. canis isolated from dogs and ticks, and all infected individuals originated from regions endemic to the ornate tick, Dermacentor reticulatus. Anaplasma phagocytophilum was found in tissue from one individual (1/50=2 %), and the sequence was assigned to the zoonotic ecotype I., (Copyright © 2023. Published by Elsevier GmbH.)

(1) Background: The purpose of the given study was to examine the antitumor activity of the simultaneous administration of MM-129, a 1,2,4-triazine derivative, and indoximod (IND), the kynurenine pathway inhibitor, toward colon cancer. (2) Methods: The efficiency of the co-administration of the studied compounds was assessed in xenografted zebrafish embryos. Then, the effects of the combined administration of compounds on cellular processes such as cell viability, apoptosis, and intracellular signaling pathways were evaluated. In vitro studies were performed using two colorectal cancer cell lines, namely, DLD-1 and HT-29. (3) Results: The results indicated that the simultaneous application of MM-129 and indoximod induced a stronger inhibition of tumor growth in zebrafish xenografts. The combination of these compounds intensified the process of apoptosis by lowering the mitochondrial potential, enhancing the externalization of phosphatidylserine (PS) and activation of caspases. Additionally, the expression of protein kinase B (AKT) and indoleamine 2,3-dioxygenase-(1IDO1) was disrupted under the applied compound combination. (4) Conclusions: Simultaneous targeting of ongoing cell signaling that promotes tumor progression, along with inhibition of the kynurenine pathway enzyme IDO1, results in the enhancement of the antitumor effect of the tested compounds against the colon cancer cells.

Factor VII activating protease (FSAP) was first isolated from human plasma less than 30 years ago. Since then, many research groups have described the biological properties of this protease and its role in hemostasis and other processes in humans and other animals. With the progress of knowledge about the structure of FSAP, several of its relationships with other proteins or chemical compounds that may modulate its activity have been explained. These mutual axes are described in the present narrative review. The first part of our series of manuscripts on FSAP describes the structure of this protein and the processes leading to the enhancement and inhibition of its activities. The following parts, II and III, concern the role of FSAP in hemostasis and in the pathophysiology of human diseases, with particular emphasis on cardiovascular diseases.

In the last few decades, there has been a growing interest in Bruton's tyrosine kinase (BTK) and the compounds that target it. BTK is a downstream mediator of the B-cell receptor (BCR) signaling pathway and affects B-cell proliferation and differentiation. Evidence demonstrating the expression of BTK on the majority of hematological cells has led to the hypothesis that BTK inhibitors (BTKIs) such as ibrutinib can be an effective treatment for leukemias and lymphomas. However, a growing body of experimental and clinical data has demonstrated the significance of BTK, not just in B-cell malignancies, but also in solid tumors, such as breast, ovarian, colorectal, and prostate cancers. In addition, enhanced BTK activity is correlated with autoimmune disease. This gave rise to the hypothesis that BTK inhibitors can be beneficial in the therapy of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), multiple sclerosis (MS), Sjögren's syndrome (SS), allergies, and asthma. In this review article, we summarize the most recent findings regarding this kinase as well as the most advanced BTK inhibitors that have been developed to date and their clinical applications mainly in cancer and chronic inflammatory disease patients.

Guidelines for cardiovascular (CV) risk assessment among young adults are uncertain. Researchers are still looking for new tools for earlier diagnosis of cardiovascular diseases (CVD), the leading cause of mortality in the modern world. This study aimed to assess whether CV risk estimation is possible in groups of healthy individuals under the age of 40 on different dietary patterns (vegans-VEGAN ( n = 48), lacto-/ovo-vegetarians-VEGE ( n = 49), pescatarians-PESCA ( n = 23), and omnivores-OMN ( n = 35)) during the pandemic period. Four metrics containing selected risk classifiers were created, and participants were assessed using them. Groups including meat consumption showed increased CV risk predictions in the metrics assessment. The next analyzes showed statistically significant relationships between the results from the created metrics and selected non-basic biomarkers for ApoA1 (OMN group, p = 0.028), IL-6 (PESCA group, p = 0.048), HCY (VEGAN group, p = 0.05), and hsCRP (OMN + PESCA groups, p = 0.025). We found that predicting CV risk among healthy people under 40 adhering to different dietary patterns, taking into account basic and non-basic laboratory assessments and created metrics, is challenging but feasible. Furthermore, the OMN group appeared to be at the highest risk of increased CV risk in the future, while risk tended to be the lowest in the VEGAN group.

Background: This study assessed how two food groups—omnivores (OMN) and vegetarians (VEGE)—differ in lifestyle changes, including dietary habits during the COVID-19 pandemic. Materials: A total of 861 persons participated in the survey and were divided into two groups: persons following a mixed diet (n = 489) and vegetarians, including vegans (n = 372). The mean age shows no significant differences. Methods: An online survey was conducted on the Polish population during the COVID-19 pandemic. Data was collected using social media; the survey was intended for adults and included separate sheets for different diets (OMN vs. VEGE). Results: The results in both groups were similar regarding the burden of premature diseases. Most respondents (~90%) did not indicate cardiovascular disease abnormalities. In the OMN group, overweight and obesity occurred more often, and the OMN group also showed a higher percentage of people reporting weight gain (OMN 42.7% vs. VEGE 35.9%). The results disclosed the VEGE group significantly more frequently chose products, i.e., vegetables (p = 0.029), legumes (p < 0.001), and dairy products or their plant substitutes (p = 0.002), compared to the OMN group. Conclusions: The VEGE group revealed the most regularities in dietary habits during the pandemic.

Pregnant obese patients are at a greater risk of developing gestational diabetes (GDM). We present a case of an obese patient who developed GDM G2 and periventricular leukomalacia in the neonate after antenatal corticosteroids (ACS) treatment. We suggest that routine blood glucose monitoring should be considered during a course of prenatal steroid therapy in all patients in a higher risk group for glucose intolerance. In cases of hyperglycemia, intensive insulin therapy should be advised. More research and new recommendations are needed on antenatal glucocorticoids (GCS), obesity, and GDM.

Background: This study assessed the possible dependencies between nutritional habits and body composition among subjects with different dietary habits. Materials: A total of 196 healthy (aged 18−50 yrs) participants were enrolled in the study and divided into 4 groups according to their diet: vegans-VEGAN (n = 53), lacto/ovo-vegetarians—VEGE (n = 52), pescatarians-PESCA (n = 28), and omnivores-OMN (n = 43). Methods: The Food Frequency Questionnaire (FFQ) was used, and body composition was assessed on the In-Body120 analyzer. Results: Our result revealed in OMN + PESCA groups a higher average consumption frequency of sweets (p = 0.024), cheese/plant cheese (p < 0.001), eggs and egg dishes/egg substitutes (p < 0.001), butter, margarine/plant margarine (p < 0.001), cream /plant cream (p = 0.018), wine and cocktails (p = 0.028), vodka (p = 0.039) and lower of natural cottage cheese/tofu/tempeh (p < 0.001), vegetable oils (p = 0.036), legumes (p < 0.001) and nuts and seeds(p < 0.001) compared to the VEGAN + VEGE groups. The body composition analysis showed significant differences in skeletal muscle mass (SMM) (p = 0.019) and the content of minerals (p = 0.048) between groups. VEGAN disclosed the lowest average values of body fat mass (BFM), percentage body fat (PBF), and visceral adipose tissue (VAT) than other studied groups. Conclusions: The body composition analysis showed mean values within normal ranges in all of the groups, but some average results of OMN, PESCA, and VEGE compared to VEGAN were not highly satisfactory (in addition to eating behavior outcomes).

A thorough understanding of cancer pathogenesis is a necessary step in the development of more effective and safer therapy. However, due to the complexity of the process and intricate interactions, studying tumor development is an extremely difficult and challenging task. In bringing this issue closer, different scientific models with various advancement levels are helpful. Cell cultures is a system that is too simple and does not allow for multidirectional research. On the other hand, rodent models, although commonly used, are burdened with several limitations. For this reason, new model organisms that will allow for the studying of carcinogenesis stages and factors reliably involved in them are urgently sought after. Danio rerio , an inconspicuous fish endowed with unique features, is gaining in importance in the world of scientific research. Including it in oncological research brings solutions to many challenges afflicting modern medicine. This article aims to illustrate the usefulness of Danio rerio as a model organism which turns out to be a powerful and unique tool for studying the stages of carcinogenesis and solving the hitherto incomprehensible processes that lead to the development of the disease.

Background and Aims: The purpose of the present study was to examine the pharmacodynamics features of MM-129 (1,2,4-triazine derivative) as a novel promising drug candidate against colon cancer., Methods: MM-129 was assessed for antitumor activity through an in vivo study on Cby.Cg-Foxn1nu/cmdb mice. The mechanistic studies investigated cellular affinity of a new 1,2,4-triazine derivative by measuring levels of intracellular/extracellular signal molecules participating in tumorigenesis., Results: The results revealed that MM-129 significantly reduced tumor growth in mice challenged with DLD-1 and HT-29 cells. It exerted the ability to inhibit intracellular molecules promoting tumorigenesis and inducing cell cycle arrest, like Akt, mTOR, and CDK2. Simultaneously, it was able to downregulate PD-L1 expression, which involves immunological self-tolerance. Combined administration of MM-129 and 5-fluorouracil (5-FU) additionally amplified these effects, which were manifest as an increase population of cells in the G0/G1 phase., Conclusions: A novel 1,2,4-triazine derivative with a dual mechanism of antitumor activity-MM-129, may act as a chemosensitizer, overcoming chemoresistance against 5-FU, the first-line agent in the chemotherapy of colon cancer.

Background: The recently discovered phenomenon that cancer cells can avoid immune response has gained scientists' interest. One of the pathways involved in this process is tryptophan (TRP) metabolism through the kynurenine pathway (KP). Individual components involved in TRP conversion seem to contribute to cancerogenesis both through a direct impact on cancer cells and the modulation of immune cell functionality. Due to this fact, this pathway may serve as a target for immunotherapy and attempts are being made to create novel compounds effective in cancer treatment. However, the results obtained from clinical trials are not satisfactory, which raises questions about the exact role of KP elements in tumorigenesis. An increasing number of experiments reveal that TRP metabolites may either be tumor promoters and suppressors and this is why further research in this field is highly needed. The aim of this study is to present KP as a modulator of cancer development through multiple mechanisms and to point to its ambiguity, which may be a reason for failures in treatment based on the inhibition of tryptophan metabolism.

Chronic kidney disease (CKD) occurrence is rising all over the world. Its presence is associated with an increased risk of premature death from cardiovascular disease (CVD). Several explanations of this link have been put forward. It is known that in renal failure, an array of metabolites cannot be excreted, and they accumulate in the organism. Among them, some are metabolites of tryptophan (TRP), such as indoxyl sulfate and kynurenine. Scientists have become interested in them in the context of inducing vascular damage in the course of chronic kidney impairment. Experimental evidence suggests the involvement of TRP metabolites in the progression of chronic kidney disease and atherosclerosis separately and point to oxidative stress generation as one of the main mechanisms that is responsible for worsening those states. Since it is known that blood levels of those metabolites increase significantly in renal failure and that they generate reactive oxygen species (ROS), which lead to endothelial injury, it is reasonable to suspect that products of TRP metabolism are the missing link in frequently occurring atherosclerosis in CKD patients. This review focuses on reports that shed a light on TRP metabolites as contributing factors to vascular damage in the progression of impaired kidney function., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2020 Iwona Kwiatkowska et al.)

The development of cancer is a problem that has accompanied mankind for years. The growing number of cases, emerging drug resistance, and the need to reduce the serious side effects of pharmacotherapy are forcing scientists to better understand the complex mechanisms responsible for the initiation, promotion, and progression of the disease. This paper discusses the modulation of the particular stages of carcinogenesis by selected physiological factors, including: acetylcholine (ACh), peroxisome proliferator-activated receptors (PPAR), fatty acid-binding proteins (FABPs), Bruton's tyrosine kinase (Btk), aquaporins (AQPs), insulin-like growth factor-2 (IGF-2), and exosomes. Understanding their role may contribute to the development of more effective and safer therapies based on new binding sites., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.

Background: Niacinamide is a stable and water-soluble form of vitamin B3, a valuable and versatile cosmetic ingredient, which is well absorbed and tolerated by the skin. A large body of literature has reported on the antioxidant and cell repair properties of niacinamide. Therefore, it has been shown to be useful in the protection of the skin against ultraviolet B (UVB) radiation and free radicals. Despite numerous hypotheses on the mechanism of vitamin B3, its protective effects have not yet been fully elucidated., Objectives: The aim of the study was to determine the protective effects of niacinamide on CHO AA8 cell line against UVB radiation. We assessed the following factors: cell death, cell cycle phase distributions, reorganization of main cytoskeletal proteins, such as F-actin, vimentin and β-tubulin, and also alterations at the ultrastructural level., Material and Methods: The material used for our research was Chinese hamster ovary cell line (CHO AA8). We used 4 research groups: 1) control cells; 2) cells treated with niacinamide; 3) cells exposed to UV radiation; and 4) cells co-incubated with niacinamide and next exposed to ultraviolet. The cell death and cell cycle were evaluated by a Tali' based-image cytometer. A fluorescence microscope was used to assess the reorganization of cytoskeletal proteins, whereas a transmission electron microscope enabled the evaluation of the alterations at the ultrastructural level of cells., Results: We showed that UV-induced apoptosis and cell cycle distributions during treatment with niacinamide resulted in a non-statistical significance in cell survival and no significant changes in the morphology and cytoskeleton in comparison to the control group. In turn, a combination of both factors led to an increase in the population of live cells and a decreased level of apoptotic cells in comparison to UV-exposed cells., Conclusions: Our results confirmed the harmful effects of UV radiation on CHO AA8 cell line. Furthermore, niacinamide can protect cells against these factors, and the mechanism of action may be related to the stabilization of the cell cytoskeleton.

Scientific communications indicate the disturbed expression of neuropeptides in the skin and serum in psoriasis vulgaris (PsV) patients. Narrow-band ultraviolet radiation (NB-UVB) is one of the systemic therapies of PsV. The aim of the study was to evaluate the influence of NB-UVB therapy on substance P (SP), calcitonin gene-related peptide (CGRP), brain-derived neurotrophic factor (BDNF), corticotropin-releasing factor (CRF) and interleukin-31 (IL-31) serum concentrations in PsV patients. 59 psoriatic patients with mean PASI (psoriasis area and severity index) 14.3 were treated with NB-UVB (20 exposures). The control group consisted of 50 healthy subjects, whose age and sex matched. In all patients, serum concentration of BDNF, CRF, IL-31 substance P and CGRP was analyzed by ELISA before the treatment and in psoriatic group the analysis was also done after 10 and 20 irradiations. In patients there was found a significantly higher concentration of IL-31 (215.3 vs. 748.6 ng/ml; p < 0.0001), SP (25.7 vs. 67.2 pg/ml; p < 0.01), CGRP (31.4 vs. 44.15 pg/ml; p < 0.01) and a lower concentration of CRF (0.89 vs. 0.426 ng/ml; p < 0.0001) and BDNF (16.39 vs. 14.15 ng/ml; p = 0.1216) in comparison with the controls. 20 NB-UVB exposures caused a significant decrease in IL-31 level (748.6 vs. 631.7 ng/ml; p < 0.0001). The NB-UVB therapy had no major effect on neuropeptides serum levels regardless of a number of irradiations. On the basis of our study it can be suggested that IL-31 is involved in pathogenesis of psoriasis and the NB-UVB therapy causes alterations in its level.