Melting glacier surfaces are increasingly affected by blooms of psychrophilic microalgae, which darken the ice and lower its albedo, accelerating melting. These microalgae contain distinct vacuoles filled with brownish pigments that were earlier described as the unusual plant phenol purpurogallin. Recently, we discovered so far unreported, large amounts of iron dissolved in aqueous extracts of the glacier ice algae Ancylonema alaskanum. Since the vacuole content was very dark but the chromatographically isolated, aforementioned phenol was only yellowish, a putative complexation of iron with purpurogallin was assumed to be the reason. Application of several protocols, including Raman microscopy on both living cells and extracts, provided strong evidence that this microalga sequesters iron and forms organic metal complexes. Consequently, substantial amounts of so far uncharacterised Fe-complexes of purpurogallin are inferred to be present in Ancylonema, and that putative polymerisation of this compound impeded an earlier analytical discovery. This finding holds significant ecological implications for cold regions. The pigmentation not only enhances the tolerance of glacier ice algae to excessive UV and visible radiation but also influences our current understanding of the biochemical iron cycle in cryosphere-dominated polar and alpine regions. Further downstream consequences of this biological iron source remain to be elucidated.

• Klíčová slova
• Raman microscopy, cryoflora, glaciers, polyphenols, secondary pigmentation,
• MeSH
• fenoly * metabolismus   chemie   MeSH
• ledový příkrov * mikrobiologie   MeSH
• mikrořasy * účinky záření   chemie   metabolismus   MeSH
• světlo MeSH
• ultrafialové záření * MeSH
• železo * metabolismus   chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• fenoly * MeSH
• železo * MeSH

Alternaria alternata is a common fungus strongly related with severe allergic asthma, with 80% of affected individuals being sensitized solely to its major allergen Alt a 1. Here, we assessed the function of Alt a 1 as an innate defense protein binding to micronutrients, such as iron-quercetin complexes (FeQ2), and its impact on antigen presentation in vitro. Binding of Alt a 1 to FeQ2 was determined in docking calculations. Recombinant Alt a 1 was generated, and binding ability, as well as secondary and quaternary structure, assessed by UV-VIS, CD, and DLS spectroscopy. Proteolytic functions were determined by casein and gelatine zymography. Uptake of empty apo- or ligand-filled holoAlt a 1 were assessed in human monocytic THP1 cells under the presence of dynamin and clathrin-inhibitors, activation of the Arylhydrocarbon receptor (AhR) using the human reporter cellline AZ-AHR. Human PBMCs were stimulated and assessed for phenotypic changes in monocytes by flow cytometry. Alt a 1 bound strongly to FeQ2 as a tetramer with calculated Kd values reaching pico-molar levels and surpassing affinities to quercetin alone by a factor of 5000 for the tetramer. apoAlt a 1 but not holoAlta 1 showed low enzymatic activity against casein as a hexamer and gelatin as a trimer. Uptake of apo- and holo-Alt a 1 occurred partly clathrin-dependent, with apoAlt a 1 decreasing labile iron in THP1 cells and holoAlt a 1 facilitating quercetin-dependent AhR activation. In human PBMCs uptake of holoAlt a 1 but not apoAlt a 1 significantly decreased the surface expression of the costimulatory CD86, but also of HLADR, thereby reducing effective antigen presentation. We show here for the first time that the presence of nutritional iron complexes, such as FeQ2, significantly alters the function of Alt a 1 and dampens the human immune response, thereby supporting the notion that Alt a 1 only becomes immunogenic under nutritional deprivation.

• Klíčová slova
• enzymatic, holo–Alt a 1, immune response, iron, major allergen Alt a 1, nutritional immunity, quercetin,
• MeSH
• alergeny * MeSH
• Alternaria metabolismus   MeSH
• bronchiální astma * MeSH
• kaseiny MeSH
• klathrin MeSH
• lidé MeSH
• quercetin MeSH
• železo metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• alergeny * MeSH
• kaseiny MeSH
• klathrin MeSH
• quercetin MeSH
• železo MeSH

Designing optimal (neo)adjuvant therapy is a crucial aspect of the treatment of non-small-cell lung carcinoma (NSCLC). Standard methods of chemotherapy, radiotherapy, and immunotherapy represent effective strategies for treatment. However, in some cases with high metastatic activity and high levels of circulating tumour cells (CTCs), the efficacy of standard treatment methods is insufficient and results in treatment failure and reduced patient survival. CTCs are seen not only as an isolated phenomenon but also a key inherent part of the formation of metastasis and a key factor in cancer death. This review discusses the impact of NSCLC therapy strategies based on a meta-analysis of clinical studies. In addition, possible therapeutic strategies for repression when standard methods fail, such as the administration of low-toxicity natural anticancer agents targeting these phenomena (curcumin and flavonoids), are also discussed. These strategies are presented in the context of key mechanisms of tumour biology with a strong influence on CTC spread and metastasis (mechanisms related to tumour-associated and -infiltrating cells, epithelial-mesenchymal transition, and migration of cancer cells).

• Klíčová slova
• CTCs, NSCLCs, curcumin, flavonoids, metastasis suppression,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH