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Introduction: Russian military's incursion into Ukraine sparked the largest refugee crisis in Europe since World War II. As Ukraine's neighboring country, Poland became the primary destination for these refugees. Ukrainians staying in Poland under the EU's Temporary Protection Directive receive humanitarian support similarly to asylum seekers, but the legal pathways, length of stay and integration processes differ significantly as the Directive provides for more immediate, collective protection without the complexity of individual asylum applications. The influx of war refugees generates extremely complex situations that health personnel, especially nurses, must face on a daily basis. Aim: Identify whether and to what extent the emergence of a large number of patients with war-related experiences constituted a source of stress for nurses, and how Polish nurses coped with this issue. Materials and method: A cross-sectional study was conducted in December 2022 in Białystok, Poland. It included 473 certified nurses working in hospitals affiliated with the District Chamber of Nurses in Białystok. Perceived Stress Scale (PSS-10) questionnaire and Mini-COPE inventory (Polish version of Carver'a BriefCOPE inventory were used in the study. Results: The average stress level among nurses was moderate, with nearly equal proportions of nurses experiencing low, medium, and high stress levels. Nurses who had contact with refugees in the last six months and/or helped them, did not present an increased level of stress - on the contrary, this level was lower. Nurses who helped refugees at work more often used a planning strategy in stressful situations, and less frequently reacted to stress using humour, religion, denial or venting. Conclusions: The greater workload and more frequent contacts between Polish nurses and Ukrainian war refugees were a factor increasing work fatigue, but, paradoxically, at the same time reducing the level of stress in a situation giving the feeling of a duty well fulfilled. Empowering nurses through greater autonomy and fostering supportive work environments, especially in crisis situations like the care of war refugees has a positive impact on coping with stress. [ABSTRACT FROM AUTHOR]

There are scientific studies indicating that the attachment of an indole moiety to the triterpene scaffold can lead to increased anticancer potential. Lipophilicity is one of the factors that may influence biological properties and is therefore an important parameter to determine for newly obtained compounds as drug candidates. In the present study, previously synthesized 3 and/or 28-indole-betulin derivatives were evaluated for lipophilicity by reversed-phase thin-layer chromatography. The experimental values of lipophilicity (logPTLC) were then subjected to correlation analysis with theoretical values of logP, as well as for selected physicochemical and pharmacokinetic parameters and anticancer activity. A toxicity test using zebrafish embryos and larvae was also conducted. High correlation was observed between the experimental and theoretical values of lipophilicity. We presented correlation equations and statistical parameters describing the relationships between logPTLC and several physicochemical and ADME parameters. We also revealed the lack of correlation between the experimental values of lipophilicity and anticancer activity. Moreover, experiments on zebrafish have confirmed no toxicity of the tested compounds, which was consistent with the results of the in silico toxicity analysis. The results demonstrated, using the example of indole derivatives of betulin, the utility of lipophilicity values in the context of predicting the biological activity of new compounds. [ABSTRACT FROM AUTHOR]

Betulonic acid (B(O)A) is a pentacyclic lupane-type triterpenoid that widely exists in plants. There are scientific reports indicating anticancer activity of B(O)A, as well as the amides and esters of this triterpenoid. In the first step of the study, the synthesis of novel amide derivatives of B(O)A containing an acetylenic moiety was developed. Subsequently, the medium-soluble compounds (EB171 and EB173) and the parent compound, i.e., B(O)A, were investigated for potential cytotoxic activity against breast cancer (MCF-7 and MDA-MB-231) and melanoma (C32, COLO 829 and A375) cell lines, as well as normal human fibroblasts. Screening analysis using the WST-1 test was applied. Moreover, the lipophilicity and ADME parameters of the obtained derivatives were determined using experimental and in silico methods. The toxicity assay using zebrafish embryos and larvae was also performed. The study showed that the compound EB171 exhibited a significant cytotoxic effect on cancer cell lines: MCF-7, A-375 and COLO 829, while it did not affect the survival of normal cells. Moreover, studies on embryos and larvae showed no toxicity of EB171 in an animal model. Compared to EB171, the compound EB173 had a weaker effect on all tested cancer cell lines and produced less desirable effects against normal cells. The results of the WST-1 assay obtained for B(O)A revealed its strong cytotoxic activity on the examined cancer cell lines, but also on normal cells. In conclusion, this article describes new derivatives of betulonic acid—from synthesis to biological properties. The results allowed to indicate a promising direction for the functionalization of B(O)A to obtain derivatives with selective anticancer activity and low toxicity. [ABSTRACT FROM AUTHOR]

Simple Summary: The discovery of the involvement of the kynurenine pathway in carcinogenesis has prompted significant changes in pharmacotherapy strategies. One such approach involves the simultaneous targeting of an ongoing process in cancer cells and inhibiting the abovementioned pathway. Based on this approach, we investigated the anticancer effect of combining a 1,2,4-triazine derivative, MM-129, together with an inhibitor of the kynurenine pathway, indoximod, in a colon cancer model. The obtained results support the efficacy of this strategy, providing a basis for future in-depth analyses. (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. [ABSTRACT FROM AUTHOR]

Psoriasis is an important disease in dermatological practice and, despite many studies, its pathogenesis is still not fully understood. Gasdermin C (GSDMC; melanoma-derived leucine zipper-containing extranuclear factor, MLZE) is a member of the gasdermin protein family. The study enrolled 60 patients with active plaque-type psoriasis and 30 volunteers without dermatoses. GSDMC concentration was assessed in serum and urine samples of all participants using ELISA. GSDMC tissue expression was assessed by immunohistochemistry. The GSDMC concentration was significantly higher in serum of patients than in controls (p < 0.001). A urinary GSDMC/creatinine ratio was significantly lower in patients than in controls (p < 0.05). Psoriatic lesions exhibited a significantly higher expression of GSDMC than nonlesional patients' skin or controls' skin (p < 0.001 , p < 0.01 , respectively). There was a positive correlation between the GSDMC serum concentration and the age of patients (R = 0.31, p = 0.015) and a negative correlation between GSDMC and RBC (R = −0.37; p = 0.0038), HGB (R = −0.26; p = 0.047), and urea concentration (R = −0.36; p = 0.04). Our study shows the potential involvement of GSDMC in psoriasis. An increased serum GSDMC and a decreased urinary GSDMC/creatinine ratio could be considered noninvasive psoriasis biomarkers, especially of local hypoxia or cell proliferation. [ABSTRACT FROM AUTHOR]

During the COVID-19 pandemic, disinfection became an integral part of everybody's life in order to avoid spreading the coronavirus. In 2021, an original anonymous online survey was carried out. The questions concerned the usage of disinfectants. The study population included 56 subjects diagnosed by a physician with hand eczema (HE-derm group) and 114 subjects with no hand skin disease diagnosed by a specialist (non-derm). The HE and non-HE groups were distinguished. Nearly 80% of the HE group, and 10% of the non-HE group, experienced worsening of hand skin lesions caused by increased skin disinfection. HE-group respondents more often declared the occurrence of new hand skin symptoms, over 80% of the subjects of this group had more than 1 new symptom (compared to nearly 40% of the non-HE group). Exacerbations of the skin disease were more frequently observed by the HE group during the pandemic. There was a statistically significant decrease of the quality of life in the HE group compared to the non-HE group during the pandemic. The COVID-19 pandemic caused an increase in the prevalence of hand skin symptoms and deterioration of the skin condition. Education on appropriate disinfection techniques and skincare, as well as early dermatological intervention, might allow us to limit the development of hand skin diseases. [ABSTRACT FROM AUTHOR]

The Bruton's tyrosine kinase (BTK) inhibitor LFM-A13 has been widely employed as an antileukemic agent, but applications in solid cancer have been found recently. The compound promotes apoptosis, has an antiproliferative effect, and increases cancer cell sensitivity to chemotherapy drugs. We decided to assess the impact of the simultaneous use of erythropoietin (Epo) and LFM-A13 on signal transduction in colon DLD-1 andHT-29 cells, aswell as in tumor xenografts. The induction of apoptosis by Epo and LFM-A-13 in the cells was confirmed by phosphatidylserine externalization, loss ofmitochondrial membrane potential, andmodulation of the expression of apoptotic protein BAX and antiapoptotic protein BCL-2 in colon adenocarcinoma cells. Nude mice were inoculated with adenocarcinoma cells and treated with Epo and LFM-A13 in order to evaluate the degree of tumor regression. The simultaneous use of Epo and LFM-A13 severely inhibited cell growth, activated apoptosis, and also inhibited tumor growth in xenografts. The addition of Epo to LFM-A13 intensified the antiproliferative effect of LFM-A13, confirmed by the loss of mitochondrial membrane potential and the accumulation of apoptotic colon cancer cells with externalized phosphatidylserine (PS). These preclinical results suggest that the combination of Epo and LFM-A13 has a high proapoptotic activity and should be tested in the clinic for the treatment of solid tumors such as colon cancer. [ABSTRACT FROM AUTHOR]

Introduction: Psoriasis is a frequent and incurable skin disease that is an important issue in contemporary dermatology, although its pathogenesis is still uncertain. Gasdermin A (GSDMA) is a member of the gasdermin protein family which are able to cause pore formation in cellular membranes leading to cell death called pyroptosis., Objective: Our aim was to investigate the role of GSDMA in psoriatic patients., Method: The study enrolled 60 patients with active plaque-type psoriasis and 30 sex- and age-matched volunteers without dermatoses. GSDMA concentration was assessed in serum and urine samples of all participants using ELISA. GSDMA tissue expression was assessed by immunohistochemistry., Results: GSDMA serum concentration was significantly higher in patients compared to controls, whereas urinary GSDMA/creatinine ratio was insignificantly lower. GSDMA tissue expression was more prominent in psoriatic plaque compared to non-lesional patients' skin and healthy skin of subjects without dermatoses. There was a strong negative correlation between GSDMA serum concentration and ALT activity. GSDMA did not correlate with PASI or psoriasis duration., Conclusions: Obtained results point to the probable involvement of GSDMA in psoriasis. GSDMA overexpression may probably lead to keratinocytes hyperproliferation and be responsible for triggering inflammation in psoriatic skin. Serum GSDMA could become psoriasis biomarker, whereas urinary GSDMA, not at this point.