Biomedical Research Foundation of the Academy of Athens

Solar Ultraviolet (UV) radiation plays a key role in many chemical and biological processes, and affects significantly human health. Excessive UV exposure may lead to adverse health effects, including sunburns, skin cancer, and cataracts, whereas moderate exposure is beneficial, e.g., by supporting vitamin D production and promoting mental well-being, among other benefits. UV radiation interacts with various atmospheric components before reaching the Earth’s surface. Photons with shorter wavelengths are absorbed at higher atmospheric layers by oxygen and tropospheric ozone, and practically only UV-A and a small part of the UV-B irradiance reach the troposphere. In the troposphere, UV is scattered by air molecules and is further attenuated by aerosols and clouds. Interactions between UV radiation and aerosols are not yet completely understood, and their parameterization constitutes a major uncertainty factor in models and satellite retrieval algorithms. Understanding these interactions is thus essential for accurately assessing UV exposure using modeled UV irradiance.Τhe purpose of this study is to evaluate satellite- and reanalysis-based retrievals of the effective dose for the cutaneous vitamin D synthesis using ground-based measurements over Athens and Thessaloniki, Greece. We evaluate data that are derived (1) using the methodology described in Fragkos et al., (2024, https://doi.org/10.3390/rs16111878), based on CAMS information in combination with satellite data from OMI and MSG, and (2) the UV climatology of which is also based on data from various sensors analyzing air quality. Ground-based spectral solar UV irradiance measurements performed with a MKIV single monochromator Brewer spectrophotometer in Athens, and a MKIII double monochromator Brewer spectrophotometer in Thessaloniki are used to validate the Satellite-based retrievals. AOD measurements from co-located CIMEL sun-photometers, part of the AERONET network are used to assess the effect of aerosols. The evaluation has been performed for the period 2004 - 2024. Further analysis yielded positive trends in the effective dose for vitamin D production in the last two decades, mainly due the decreasing trends in aerosols.

Objectives Monocytes play versatile roles in host defense, inflammation regulation and immune activation and are key effector cells in human systemic lupus erythematosus (SLE).Overproduction of cytokines, self-antigen presentation and amplification of tissue inflammation represent outcomes of transcriptional rewiring within the inflammatory milieu of the disease.This study aimed to delineate the altered transcriptome of monocytes in SLE, investigate how epitranscriptomic RNA editing affects their function, and assess whether transcriptional perturbations are linked to changes in chromatin organization.Methods Monocytes from 8 SLE patients (SLEDAI >8) and 5 age-and sex-matched healthy controls were isolated from PBMCs by Ficoll centrifugation and CD14+ magnetic bead selection.Single-end 75-bp mRNA sequencing was performed, and differential expression was analyzed using edgeR (p-value < 0.05, fold change >1.5), followed by pathway enrichment analysis with clusterProfiler.A trained immunity signature was constructed from publicly available data and compared with our experiment.A-to-I RNA editing events were profiled with JACUSA2, retaining high-confidence sites (score > 2.5) present in REDIportal and significant differences in editing frequency (Wilcoxon rank-sum test, p < 0.05).Domains of Coordinated Expression (DCEs), defined as genomic regions of consecutive chromosomal bin with gene expression correlation above healthy average, were estimated to examine whether altered gene expression patterns correspond to chromatin organization changes.Results A total of 1,368 differentially expressed genes (DEGs) were identified, including 761 upregulated and 607 downregulated in SLE monocytes.Upregulated DEGs were enriched in pathways related to biotic stimulus response, cell chemotaxis, T-cell differentiation, RNA polymerase function, and IL-17 signaling.Our genes showed correlation with trained immunity.Interestingly ADARB1, a key regulator of RNA editing, was upregulated, and SLE monocytes exhibited significantly increased A-to-I editing frequencies, particularly in immune-related genes such as ARPC2, IL17RA, TLR2, and OSCAR.Most editing sites were in the UTR3 and intronic regions.DCE analysis revealed extensive redistribution of chromatin co-expression activity, indicating rearrangement of transcriptional coordination.Conclusions SLE monocytes exhibit widespread transcriptional changes.These findings highlight RNA editing as an addition-al player of immune-related epigenetic memory of monocytes while chromatin disorganization amplifies transcriptional dysregulation.Collectively, these alterations integrate inflammatory cues and enhance the autoimmune identity characteristic of the disease.

Numerous geneticvariants have been identified by genome-wide associationstudies as being associated with colorectal cancer (CRC) risk. Metabolome-wideassociation analysis was performed for 187 CRC-associated geneticvariants using genomic data and untargeted 1H nuclear magneticresonance urine metabolomics from 1951 Airwave Health Monitoring Studyparticipants. We identified statistically significant associationsbetween seven CRC single-nucleotide polymorphisms (SNPs) and urinarymetabolites. This included SNPs within or close to RHPN2 with sucrose (P = 1.2 × 10–7), SLC6A18 with amino acids (P =6.9 × 10–5 with tyrosine, P = 9.9 × 10–5 with leucine), and MAP2K5 and BMP2 with gut microbial metabolites (P = 1.6 × 10–4 and P = 4.4 × 10–4). The most significant correlationwas followed by functional experiments in Caco-2 colon cancer cells.CRISPR-mediated knockout of a 48-nt RHPN2 intronicregion containing rs10411210 in colon cancer cells compromised cellgrowth. RNA sequencing was performed in the two sets of clones (3edited and 3 unedited) followed by pathway enrichment, and gene ontologyanalysis depicted extensive deregulation of genes (448 up- and 195downregulated) involved in cell division and several metabolic processes.Overall, these findings demonstrate that integrating genetic and metabolomicdata highlights the importance of the RHPN2 introniclocus in CRC potentially through metabolic processes affecting excretionof dietary and other metabolites.

In this article a comparative statement regarding the frequency of GBA1 variants in the Cretan Parkinson's disease (PD) cohort versus the Greek mainland was overstated in wording.This issue concerns interpretation in the Abstract and Discussion section only.In the Abstract the statement was "The proportion of GBA1 in Crete is substantially higher than on the Greek mainland, highlighting the distinct genetic PD profile in this population and supporting targeted genetic testing and counseling." and should have read "The proportion of GBA1 in Crete highlights the distinct genetic PD profile in this population and supports targeted genetic testing and counseling." and in the Discussion section the statement was "This proportion is substantially higher than previous estimates of GBA1 frequency in the mainland Greek population (~4%), and more closely resembles reports of Greek familial PD cohorts (10.3%)." and should have read "This proportion is comparable to previous estimates of GBA1 frequency in the mainland Greek population".

Abstract Prostate cancer (PCa) is an androgen receptor (AR) driven, high-incidence disease significantly contributing to cancer mortality. PCa is in need of better risk stratification at diagnosis and treatment outcomes in patients at high risk of metastasis. The unfolded protein response (UPR) is an AR-dependent process. However, the impact of the UPR transducer IRE1 on AR-dependent biology and treatment resistance has not been defined. We use diverse pre-clinical models of stress response to describe IRE1 activity impact on multiple disease stages and demonstrate its involvement with poor prognosis (RB1 loss), and cell lineage determination (club phenotypes). We genetically and pharmacologically perturbed AR and IRE1 activity in multiple pre-clinical PCa models and observed that long-term adaptation to IRE1 activity loss, leads to a lineage shift that confers treatment resistance characteristics in AR sensitive models. In parallel, we show that castration resistant PCa (CRPC) models have low IRE1 activity and that androgen deprivation therapy (ADT) suppresses IRE1 activity. By treating these CRPC models with an IRE1 activator, we sensitised them to both physiological and pharmacological (Enzalutamide) ADT. Integrating clinical, pre-clinical, bulk, single cell and spatial transcriptomic datasets, we chart IRE1 activity throughout PCa evolution by developing an IRE1 activity gene set (IRE1_18) reflecting both tumoral and micro-environmental niches. IRE1_18 has distinct expression profiles in AR positive (HSPC and CRPC) and AR negative (CRPC) disease reflecting tumoral identity as well as tumoral content. Using diverse datasets such as the Dream Team West Coast, META855 and 55K GRID cohorts we validated IRE1_18 against multiple clinical correlates. As such, IRE1_18 significantly correlates with response to ARSI, grade group, NCCN and Decipher scores. Finally, it prognosticas localised and metastatic disease independently from AR activity in terms of metastatic progression, biochemical recurrence, prostate cancer specific mortality and consequently, may guide IRE1 modulation as a novel combination therapeutic. Our study showcases a forward translation, data integration pipeline which may distil actionable targets and biomarkers from studying a fundamental biological homeostatic mechanism that represents cells in both the tumour and the microenvironment. Citation Format: Dimitrios Doultsinos, Ingrid Tomljanovic, Eleftherios Pilalis, Sophia Abusamra, Sandy Figiel, Romuald Parmentier, Imogen Bridges, Joanna Hester, Yanis Zekri, Damien Leach, Charlotte Bevan, Alastair Lamb, Wilbert Zwart, Aristotelis Chatziioannou, Clementine Le Magnen, Mohammed Alshalalfa, Elai Davicioni, Rensheng Wan, David Quigley, Alfonso Urbanucci, JP Theurillat, Jichang Zhang, Ian Mills. Integrating multi-omic datasets investigating stress response biology decodes prostate cancer dynamic disease progression and places IRE1 activity at the epicentre of acquired treatment resistance [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Innovations in Prostate Cancer Research and Treatment; 2026 Jan 20-22; Philadelphia PA. Philadelphia (PA): AACR; Cancer Res 2026;86(2_Suppl):Abstract nr PR030.

In this work, we present three different pathways to render commercial melamine sponges, both magnetic and hydrophobic, thereby offering them the capacity to effectively and selectively remove crude oil and heavy metals from aqueous environments.

Abstract. Dust particles originating from desert areas of the planet have significant radiative impacts on the ground and atmospheric column, changing the energy distribution of the entire earth system, which cannot be underestimated, as dust is considered a climatic regulator. The magnitude of the dust radiative effect is dependent on the optical properties of desert dust aerosols, which in turn is regulated by the composition and mineralogical content of desert dust plumes. The mineralogical composition in atmospheric models is commonly related to the soil type at dust sources and the optical properties needed are provided by observational campaigns and dedicated measurements. In this work we upgrade the METAL-WRF model to incorporate the direct radiative impact of the minerals in dust and test the impact of the direct radiative feedback on a 2-month simulation period, namely March and April 2022, when consecutive intense dust outbursts affected the Mediterranean Basin. The simulation results were compared against Global Horizontal Irradiance data and AERONET optical properties that were measured at five sites. An improvement was observed in all sites, especially close to the sources, when the minerals and dust are treated as interacting in the radiative transfer calculations, thus improving the capabilities of METAL-WRF to simulate the chemical composition of dust particles in the atmosphere along with their contribution to radiative transfer processes.

The authors have retracted this article. After publication, concerns were raised regarding high similarity between the electron microscopy images in this article and several earlier articles [1,2,3], as well as image overlap in Fig. 2D (α-syn alone and CMC11 2:1). The original electron microscopy source files are unavailable for validation, and the authors therefore no longer have confidence in the integrity of the electron microscopy figures.

Abstract Background and Aims The heart and kidneys are vital organs that influence each other's function. Dysfunction in one inevitably leads to dysfunction in the other and is known as cardiorenal syndrome (CRS). CRS type 4 is defined by chronic kidney disease (CKD) causing impaired cardiac function, primarily through diastolic dysfunction and structural remodelling, including fibrosis and hypertrophy. This is accompanied by metabolic alterations, characterized by disrupted energy substrate utilization and a metabolic shift towards glycolysis instead of beta-oxidation. The progression of CRS IV occurs dynamically and gradually thus identifying key changes could prove beneficial for treatment and prediction of outcome for the patients. The present study assessed heart remodelling and function after 12 and 24 weeks of chronic kidney disease in rats undergoing subtotal nephrectomy (respectively SNx12 and SNx24). Method At 12 weeks, male Sprague Dawley rats underwent 5/6 nephrectomy (SNx) or Sham operation and were sacrificed after 12 or 24 weeks. Serum creatinine was measured with the epoc® Blood Analysis System. Before sacrifice, a carotid artery catheter was inserted to measure systolic arterial pressure (SAP). Left ventricular function was assessed by echocardiography (VisualSonics/Fujifilm) under isoflurane anaesthesia. Fibrosis (Sirius Red staining) in both kidney and heart, and cardiomyocyte size (H&amp;E staining) were quantified. Vevolab 3.1.0 software was used to evaluate left ventricle posterior wall thickness during systole (LVPW_S), diastolic dysfunction by measurement of isovolumic relaxation time (IVRT), early diastolic strain rate (E/SRE) and Doppler mitral inflow velocities of the peak early (E) ‘/ Tissue doppler parameter e′ (E/e’). To further assess molecular alterations in the left ventricle, proteomics analysis was performed using LC-MS/MS method (n = 5 animals from each of Sham and SNx groups). Samples were prepared according to FASP protocol. Gene Set Variation Analysis (GSVA) was conducted using pathway terms from the Molecular Signatures Database and results were analysed using the limma method. Statistical analysis and GSVA was performed using GraphPad Prism 8 and R Studio, two-way ANOVA, non-parametric tests, with log transformation when applicable. Results Plasma creatinine levels were increased in both SNx12 and SNx24 animals (Table 1). Fibrosis in the kidney increased between SNx12 and SNx24 versus their corresponding Sham (Table 1). SNx24 rats exhibited increased heart fibrosis, cardiomyocyte size, and SAP in comparison to the respective Sham (Table 1). Cardiac remodelling between SNx12 and SNx24 was observed through the increase in the left ventricle wall thickness (Fig. 1A). In SNx24 diastolic dysfunction was observed through measurement of E/SRE, IVRT and E/e’ (Fig. 1B, Table 1). To better understand the molecular changes that correspond to pronounced hypertrophy and diastolic dysfunction, LC-MS/MS analysis was performed with a focus on the group SNx24. A heatmap was generated to illustrate top 20 up- and top 20 down-regulated proteins of SNx24 versus Sham 24 (Fig. 1C). When compared to Sham24, GSVA results indicated that SNX24 samples were associated with disrupted mitochondrial processes, downregulation of fatty acid oxidation, but also with overactivation of extracellular pathways including infiltration of immune cells, wound healing and cell-ECM interactions (Fig. 1D). Conclusion These results indicate that the SNx model captures key events in CRS development, cardiac remodelling and dysfunction, and suggest that the observed mitochondrial changes play a supportive role in these processes. This preclinical model also provides an opportunity to evaluate novel anti-fibrotic treatments and assess their impact on mitochondrial function, paving the way for potential therapeutic advancements.