Adoracja Matki Boskiej w asyście dwóch świętych Janów w zbiorach Katedry Wawelskiej

There is a canvas (98,5 x 222,5cm) in the Wawel Cathedral that is not connected with any existing or historically documented altars inside the church (il. 1-3). Owing to its shape it has so far been considered to have been a predella, which - taking into account its size and proportions - seems rather unlikely. It may have been the top of the middle part of a retable, possibly in an altar dedicated to the two St. Johns. The painting presents the Virgin Mary with the Child seated under a canopy, attended by the two Saints, adored by kneeling angels with censers in their hands. A graphic model of the scene has been found; it is an engraving by Jan Sadeler (1550-1600) based on a design by Hans von Aachen (1552-1615), released in Munich in 1589 (il. 4). In Albertina, in Vienna, a working copy of the graphic made by Hans von Aachen has been preserved (il. 5) as well as a composition sketch by the same artist at the Herzog Anton Ulrich-Museum in Braunschweig. An inscription on the drawing from 1589 reads: POENA ET PROEMIVM; there are also quotations from psalms and a dedication to Phillip Wilhelm (1576-1598), bishop of Regenzburg in 1589, later cardinal (1596), son of a Bavarian ruler Wilhelm V Wittelsbach (1548-1626). The young hierarch got it in the year of his consecration as a bishop. A pendant to it is the plate by Jan Sadeler of 1590, after Peter Candid (1548-1628), which was dedicated to Phillip Wilhelm’s younger brother - Ferdinand (1577-1650), later bishop of Cologne. The engraving also shows St. Mary with the Child in the company of St. Stephen and St. Laurence. Both works coincide with the artistic activity of Jan Sadeler and Hans von Achen in Munich, where they were summoned by Wilhelm V, and represent strictly planned art created for his court. Another painted version of Sadeler’s engraving was found in a Polish private collection. This is a small, good painting on panel, faithfully reproducing physiognomy and inscriptions known from the prototype. The picture in the Wawel Cathedral, probably painted in Cracow between 1600-1630 and based on the Munich model, is one of the examples of assimilating mannerist engravings from southern Germany in the Cracow environment. Their large influx into Little Poland at the end of the 16th and the beginning of the 17th century may be connected with animated contacts of Sigismund I ll’s court with Bavaria and its artistic centres such as Augsburg, the main purveyor of goldsmith’s work for the Polish king’s court.W katedrze na Wawelu znajduje się obraz na płótnie, w kształcie wydłużonego prostokąta o półkolistych zakończeniach z kwadratowymi wykrojami w narożnikach, formatem zbliżony do predelli. Izolowane dzieło, nie związane z żadnym z istniejących ołtarzy, nie występuje w inwentarzach i nie ma - jak dotąd - potwierdzonej katedralnej metryki. Jego obecność w świątyni może łączyć się z akcją gromadzenia zabytków sakralnych podjętą około roku 1900, z myślą o utworzeniu w Krakowie Muzeum Diecezjalnego. Wobec milczenia źródeł domniemana proweniencja spoza katedry, z szeroko pojętego terenu Małopolski, wydaje się bardziej prawdopodobna niż odłączenie malowidła od któregoś z wawelskich ołtarzy

Dynamic interactions in the tumor niche: how the cross-talk between CAFs and the tumor microenvironment impacts resistance to therapy

The tumor microenvironment (TME) is a complex ecosystem of cells, signaling molecules, and extracellular matrix components that profoundly influence cancer progression. Among the key players in the TME, cancer-associated fibroblasts (CAFs) have gained increasing attention for their diverse and influential roles. CAFs are activated fibroblasts found abundantly within the TME of various cancer types. CAFs contribute significantly to tumor progression by promoting angiogenesis, remodeling the extracellular matrix, and modulating immune cell infiltration. In order to influence the microenvironment, CAFs engage in cross-talk with immune cells, cancer cells, and other stromal components through paracrine signaling and direct cell-cell interactions. This cross-talk can result in immunosuppression, tumor cell proliferation, and epithelial-mesenchymal transition, contributing to disease progression. Emerging evidence suggests that CAFs play a crucial role in therapy resistance, including resistance to chemotherapy and radiotherapy. CAFs can modulate the tumor response to treatment by secreting factors that promote drug efflux, enhance DNA repair mechanisms, and suppress apoptosis pathways. This paper aims to understand the multifaceted functions of CAFs within the TME, discusses cross-talk between CAFs with other TME cells, and sheds light on the contibution of CAFs to therapy resistance. Targeting CAFs or disrupting their cross-talk with other cells holds promise for overcoming drug resistance and improving the treatment efficacy of various cancer types

Insight into the Leukemia Microenvironment and Cell-cell Interactions Using Flow Cytometry

Cancer cells, including leukemia cells, reside in a complex microenvironment, which influences biology and activity of the cells. The protective role of bone marrow stromal cells is already commonly recognized. Remodeling of stroma cell functions by leukemia cells is also well documented. In this respect, different routes of interactions were defined, such as direct cell-cell interactions or indirect cross talk, by release of soluble factors or vesicular particles containing proteins, RNAs and other molecules. Since intercellular communication seems to play a role in various biological processes, it might be important to conduct studies in co-culture systems, which at least mimic partially more physiological conditions, and enables this intercellular exchange to occur. Thus, it is crucial to improve analytical methods of investigation of co-cultured cells, to study their interactions and so to understand biology of leukemia in order to understand molecular mechanisms and offer novel therapeutic strategies. The present chapter outlines the importance of modern, multiparameter flow cytometry methods, which allow to analyze interactions between different types of cells within the leukemia microenvironment. Importantly, the proposed experimental setups can be easily transformed to study different cell types and different biological systems

Targeting of Post-Transcriptional Regulation as Treatment Strategy in Acute Leukemia

Post-transcriptional regulation is an important step of gene expression that allows to fine-tune the cellular protein profile (so called proteome) according to the current demands. That mechanism has been developed to aid survival under stress conditions, however it occurs to be hijacked by cancer cells. Adjustment of the protein profile remodels signaling in cancer cells to adapt to therapeutic treatment, thereby enabling persistence despite unfavorable environment or accumulating mutations. The proteome is shaped at the post-transcriptional level by numerous mechanisms such as alternative splicing, mRNA modifications and triage by RNA binding proteins, change of ribosome composition or signaling, which altogether regulate the translation process. This chapter is an overview of the translation disturbances found in leukemia and their role in development of the disease, with special focus on the possible therapeutic strategies tested in acute leukemia which target elements of those regulatory mechanisms

Tunneling nanotube-mediated intercellular vesicle and protein transfer in the stroma-provided imatinib resistance in chronic myeloid leukemia cells

Intercellular communication within the bone marrow niche significantly promotes leukemogenesis and provides protection of leukemic cells from therapy. Secreted factors, intercellular transfer of mitochondria and the receptor–ligand interactions have been shown as mediators of this protection. Here we report that tunneling nanotubes (TNTs)—long, thin membranous structures, which have been identified as a novel mode of intercellular cross-talk—are formed in the presence of stroma and mediate transfer of cellular vesicles from stroma to leukemic cells. Importantly, transmission of vesicles via TNTs from stromal cells increases resistance of leukemic cells to the tyrosine kinase inhibitor, imatinib. Using correlative light-electron microscopy and electron tomography we show that stromal TNTs contain vesicles, provide membrane continuity with the cell bodies and can be open-ended. Moreover, trans-SILAC studies to reveal the non-autonomous proteome showed that specific sets of proteins are transferred together with cellular vesicles from stromal to leukemic cells, with a potential role in survival and adaptation. Altogether, our findings provide evidence for the biological role of the TNT-mediated vesicle exchange between stromal and leukemic cells, implicating the direct vesicle and protein transfer in the stroma-provided protection of leukemic cells

Remodeling of T Cell Dynamics During Long COVID Is Dependent on Severity of SARS-CoV-2 Infection

Several COVID-19 convalescents suffer from the post-acute COVID-syndrome (PACS)/long COVID, with symptoms that include fatigue, dyspnea, pulmonary fibrosis, cognitive dysfunctions or even stroke. Given the scale of the worldwide infections, the long-term recovery and the integrative health-care in the nearest future, it is critical to understand the cellular and molecular mechanisms as well as possible predictors of the longitudinal post-COVID-19 responses in convalescent individuals. The immune system and T cell alterations are proposed as drivers of post-acute COVID syndrome. However, despite the number of studies on COVID-19, many of them addressed only the severe convalescents or the short-term responses. Here, we performed longitudinal studies of mild, moderate and severe COVID-19-convalescent patients, at two time points (3 and 6 months from the infection), to assess the dynamics of T cells immune landscape, integrated with patients-reported symptoms. We show that alterations among T cell subsets exhibit different, severity- and time-dependent dynamics, that in severe convalescents result in a polarization towards an exhausted/senescent state of CD4+ and CD8+ T cells and perturbances in CD4+ Tregs. In particular, CD8+ T cells exhibit a high proportion of CD57+ terminal effector cells, together with significant decrease of naïve cell population, augmented granzyme B and IFN-γ production and unresolved inflammation 6 months after infection. Mild convalescents showed increased naïve, and decreased central memory and effector memory CD4+ Treg subsets. Patients from all severity groups can be predisposed to the long COVID symptoms, and fatigue and cognitive dysfunctions are not necessarily related to exhausted/senescent state and T cell dysfunctions, as well as unresolved inflammation that was found only in severe convalescents. In conclusion, the post-COVID-19 functional remodeling of T cells could be seen as a two-step process, leading to distinct convalescent immune states at 6 months after infection. Our data imply that attenuation of the functional polarization together with blocking granzyme B and IFN-γ in CD8+ cells might influence post-COVID alterations in severe convalescents. However, either the search for long COVID predictors or any treatment to prevent PACS and further complications is mandatory in all patients with SARS-CoV-2 infection, and not only in those suffering from severe COVID-19

Primary cancer-associated fibroblasts exhibit high heterogeneity among breast cancer subtypes

Background: Cancer-associated fibroblasts (CAFs) are a diverse subset of cells, that is recently gaining in popularity and have the potential to become a new target for breast cancer therapy; however, broader research is required to understand their mechanisms and interactions with breast cancer cells. The goal of the study was to isolate CAFs from breast cancer tumour and characterise isolated cell lines. We concentrated on numerous CAF biomarkers that would enable their differentiation.  Materials and methods: Flow cytometry, immunofluorescence, and reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) were used to phenotype the primary CAFs. Conclusions: According to our findings, there was no significant pattern in the classification of cancer-associated fibroblasts. The results of biomarkers expression were heterogeneous, thus no specific subtypes were identified. Furthermore, a comparison of cancer-associated fibroblasts derived from different BC subtypes (luminal A and B, triple-negative, HER2 positive) did not  reveal any clear trend of expression