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Úvod: Metody časného odstranění trombu byly do praxe zavedeny s cílem zefektivnit léčbu hluboké žilní trombózy (HŽT). Prezentujeme zkušenosti s farmakomechanickou trombektomií (PMT) u souboru pacientů s akutní ileofemorální (IF) HŽT. Metodika: U 46 pacientů (16 mužů a 30 žen ve věkovém rozmezí 16-75 let) s akutní IF HŽT byla provedena PMT pomocí zařízení AngioJet, v 80 % v kombinaci s následnou katétrem řízenou lokální trombolýzou (CDT). Průchodnost rekanalizova-ného úseku byla kontrolována pomocí UZ před dimisí a následně za 3 měsíce, 12 měsíců a dále jednou ročně. Získaná data byla analyzována retrospektivně. Výsledky: Rekanalizace bylo dosaženo u všech pacientů, ve 20 % při primární PMT, v 80 % po následné CDT, ve 43 % byl zaveden žilní stent. Medián celkového množství podaného trombolytika (Actilyse, Boehringer Ingelheim, Francie) byl 32,5 mg. Medián celkové délky endovaskulární léčby byl 20,5 hodin a doby hospitalizace 5 dnů. Fatální hemoragická komplikace vznikla u jednoho pacienta (2 %). Nezávažné klinicky relevantní krvácení se objevilo u tří pacientů (6,5 %). U dvou pacientů došlo k uzávěru pánevních stentů 6 a 12 měsíců po léčbě. Průchodnost rekanalizovaného úseku zůstala zachována v 92 % (kontrola s časovým odstupem v mediánu 12 měsíců od zákroku). Závěr: V našem souboru jsme prokázali vysokou efektivitu léčby IF HŽT pomocí PMT. Incidence závažných krvácivých kom-plikacíje nízká, může však mít fatální následky. [ABSTRACT FROM AUTHOR]

Fibrosis contributes to tissue repair, but excessive fibrosis disrupts organ function. Alagille syndrome (ALGS, caused by mutations in JAGGED1) results in liver disease and characteristic fibrosis. Here, we show that Jag1 Ndr/Ndr mice, a model for ALGS, recapitulate ALGS-like fibrosis. Single-cell RNA-seq and multi-color flow cytometry of the liver revealed immature hepatocytes and paradoxically low intrahepatic T cell infiltration despite cholestasis in Jag1 Ndr/Ndr mice. Thymic and splenic regulatory T cells (Tregs) were enriched and Jag1 Ndr/Ndr lymphocyte immune and fibrotic capacity was tested with adoptive transfer into Rag1 -/- mice, challenged with dextran sulfate sodium (DSS) or bile duct ligation (BDL). Transplanted Jag1 Ndr/Ndr lymphocytes were less inflammatory with fewer activated T cells than Jag1 +/+ lymphocytes in response to DSS. Cholestasis induced by BDL in Rag1 -/- mice with Jag1 Ndr/Ndr lymphocytes resulted in periportal Treg accumulation and three-fold less periportal fibrosis than in Rag1 -/- mice with Jag1 +/+ lymphocytes. Finally, the Jag1 Ndr/Ndr hepatocyte expression profile and Treg overrepresentation were corroborated in patients' liver samples. Jag1-dependent hepatic and immune defects thus interact to determine the fibrotic process in ALGS., (© 2024. The Author(s).)

Dry spells strongly influence biomass production in forest ecosystems. Their effects may last several years following a drought event, prolonging growth reduction and therefore restricting carbon sequestration. Yet, our understanding of the impact of dry spells on the vitality of trees' above-ground biomass components (e.g., stems and leaves) at a landscape level remains limited. We analyzed the responses of Pinus sylvestris and Picea abies to the four most severe drought years in topographically complex sites. To represent stem growth and canopy greenness, we used chronologies of tree-ring width and time series of the Normalized Difference Vegetation Index (NDVI). We analyzed the responses of radial tree growth and NDVI to dry spells using superposed epoch analysis and further explored this relationship using mixed-effect models. Our results show a stronger and more persistent response of radial growth to dry spells and faster recovery of canopy greenness. Canopy greenness started to recover the year after the dry spell, whereas radial tree growth remained reduced for the two subsequent years and did not recover the pre-drought level until the fourth year after the event. Stem growth and canopy greenness were influenced by climatic conditions during and after drought events, while the effect of topography was marginal. The opposite responses of stem growth and canopy greenness following drought events suggest a different impact of dry spells on trees´ sink and source compartments. These results underscore the crucial importance of understanding the complexities of tree growth as a major sink of atmospheric carbon., (© 2024. The Author(s).)

Traditionally, anticancer therapies focus on restraining uncontrolled proliferation. However, these cytotoxic therapies expose cancer cells to direct killing, instigating the process of natural selection favoring survival of resistant cells that become the foundation for tumor progression and therapy failure. Recognizing this phenomenon has prompted the development of alternative therapeutic strategies. Here we propose strategies targeting cancer hallmarks beyond proliferation, aiming at re-educating cancer cells towards a less malignant phenotype. These strategies include controlling cell dormancy, transdifferentiation therapy, normalizing the cancer microenvironment, and using migrastatic therapy. Adaptive resistance to these educative strategies does not confer a direct proliferative advantage to resistant cells, as non-resistant cells are not subject to eradication, thereby delaying or preventing the development of therapy-resistant tumors., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

To enhance our understanding of forest carbon sequestration, climate change mitigation and drought impact on forest ecosystems, the availability of high-resolution annual forest growth maps based on tree-ring width (TRW) would provide a significant advancement to the field. Site-specific characteristics, which can be approximated by high-resolution Earth observation by satellites (EOS), emerge as crucial drivers of forest growth, influencing how climate translates into tree growth. EOS provides information on surface reflectance related to forest characteristics and thus can potentially improve the accuracy of forest growth models based on TRW. Through the modelling of TRW using EOS, climate and topography data, we showed that species-specific models can explain up to 52 % of model variance (Quercus petraea), while combining different species results in relatively poor model performance (R 2  = 13 %). The integration of EOS into models based solely on climate and elevation data improved the explained variance by 6 % on average. Leveraging these insights, we successfully generated a map of annual TRW for the year 2021. We employed the area of applicability (AOA) approach to delineate the range in which our models are deemed valid. The calculated AOA for the established forest-type models was 73 % of the study region, indicating robust spatial applicability. Notably, unreliable predictions predominantly occurred in the climate margins of our dataset. In conclusion, our large-scale assessment underscores the efficacy of combining climate, EOS and topographic data to develop robust models for mapping annual TRW. This research not only fills a critical void in the current understanding of forest growth dynamics but also highlights the potential of integrated data sources for comprehensive ecosystem assessments., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Stilbenes in food and medicinal plants have been described as potent antiphlogistic and antioxidant compounds, and therefore, they present an interesting potential for the development of dietary supplements. Among them, macasiamenene F (MF) has recently been shown to be an effective anti-inflammatory and cytoprotective agent that dampens peripheral and CNS inflammation in vitro . Nevertheless, this promising molecule, like other stilbenes and a large percentage of drugs under development, faces poor water solubility, which results in trickier in vivo administration and low bioavailability. With the aim of improving MF solubility and developing a form optimized for in vivo administration, eight types of conventional liposomal nanocarriers and one type of PEGylated liposomes were formulated and characterized. In order to select the appropriate form of MF encapsulation, the safety of MF liposomal formulations was evaluated on THP-1 and THP-1-XBlue-MD2-CD14 monocytes, BV-2 microglia, and primary cortical neurons in culture. Furthermore, the cellular uptake of liposomes and the effect of encapsulation on MF anti-inflammatory effectiveness were evaluated on THP-1-XBlue-MD2-CD14 monocytes and BV-2 microglia. MF (5 mol %) encapsulated in PEGylated liposomes with an average size of 160 nm and polydispersity index of 0.122 was stable, safe, and the most promising form of MF encapsulation keeping its cytoprotective and anti-inflammatory properties., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Notch signaling controls multiple aspects of embryonic development and adult homeostasis. Alagille syndrome is usually caused by a single mutation in the jagged canonical Notch ligand 1 (JAG1), and manifests with liver disease and cardiovascular symptoms that are a direct consequence of JAG1 haploinsufficiency. Recent insights into Jag1/Notch-controlled developmental and homeostatic processes explain how pathology develops in the hepatic and cardiovascular systems and, together with recent elucidation of mechanisms modulating liver regeneration, provide a basis for therapeutic efforts. Importantly, disease presentation can be regulated by genetic modifiers, that may also be therapeutically leverageable. Here, we summarize recent insights into how Jag1 controls processes of relevance to Alagille syndrome, focused on Jag1/Notch functions in hepatic and cardiovascular development and homeostasis., Competing Interests: Declaration of competing interest Two projects in ERA lab, not directly related to the content of this review, are/were supported by modeRNA and Travere. No personal remuneration., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Variations in the growth of aboveground biomass compartments such as tree stem and foliage significantly influence the carbon cycle of forest ecosystems. Yet the patterns of climate-driven responses of stem and foliage and their modulating factors remain poorly understood. In this study, we investigate the climatic response of Norway spruce (Picea abies) at 138 sites covering wide spatial and site fertility gradients in temperate forests in Central Europe. To characterize the annual growth rate of stem biomass and seasonal canopy vigor, we used tree-ring chronologies and time-series of NDVI derived from Landsat imagery. We calculated correlations of tree-ring width and NDVI with mean growing season temperature and standardized precipitation evapotranspiration index (SPEI). We evaluated how these climate responses varied with aridity index, soil category, stand age, and topographical factors. The results show that the climate-growth responses of tree rings shift from positive to negative for SPEI and from negative to positive for temperature from dry (warm) to wet (cold) areas. By contrast, NDVI revealed a negative response to temperature across the entire climatic gradient. The negative response of NDVI to temperature likely results from drought effects in warm areas and supporting effects of cloudy conditions on foliage greenness in wet areas. Contrary to NDVI, climate responses of tree rings differed according to stand age and were unaffected by local topographical features and soil conditions. Our findings demonstrate that the decoupling of stem and foliage climatic responses may result from their different climatic limitation along environmental gradients. These results imply that in temperate forest ecosystems, the canopy vigor may show different trends compared to stem growth under ongoing climate change., Competing Interests: Declaration of competing interest The author declares no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Temperate forests are undergoing significant transformations due to the influence of climate change, including varying responses of different tree species to increasing temperature and drought severity. To comprehensively understand the full range of growth responses, representative datasets spanning extensive site and climatic gradients are essential. This study utilizes tree-ring data from 550 sites from the temperate forests of Czechia to assess growth trends of six dominant Central European tree species (European beech, Norway spruce, Scots pine, silver fir, sessile and pedunculate oak) over 1990-2014. By modeling mean growth series for each species and site, and employing principal component analysis, we identified the predominant growth trends. Over the study period, linear growth trends were evident across most sites (56% increasing, 32% decreasing, and 10% neutral). The proportion of sites with stationary positive trends increased from low toward high elevations, whereas the opposite was true for the stationary negative trends. Notably, within the middle range of their distribution (between 500 and 700 m a.s.l.), Norway spruce and European beech exhibited a mix of positive and negative growth trends. While Scots pine growth trends showed no clear elevation-based pattern, silver fir and oaks displayed consistent positive growth trends regardless of site elevation, indicating resilience to the ongoing warming. We demonstrate divergent growth trajectories across space and among species. These findings are particularly important as recent warming has triggered a gradual shift in the elevation range of optimal growth conditions for most tree species and has also led to a decoupling of growth trends between lowlands and mountain areas. As a result, further future shifts in the elevation range and changes in species diversity of European temperate forests can be expected., (© 2024 John Wiley & Sons Ltd.)