Elżbieta Płuciennik

Recent advances in micronutrient biology have highlighted the pleiotropic roles of vitamins D and K in central nervous system (CNS) health and disease. Beyond their classical functions in calcium homeostasis, both vitamins exhibit regulatory effects on inflammation, oxidative stress, mitochondrial function, and gene expression, positioning them as potential modulators in neuro-oncology and neurodegeneration. In gliomas, vitamin D has been shown to influence tumour cell proliferation, differentiation, and apoptosis through vitamin D receptor (VDR)-mediated signalling, while vitamin K—particularly menaquinone—may influence glioma biology through vitamin K-dependent proteins, sphingolipid metabolism, and ferroptosis-related pathways. In neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases, deficiencies in vitamins D and K have been associated with increased neuroinflammation, impaired neuronal survival, and dysregulated protein aggregation. Emerging evidence also suggests that these vitamins play a role in brain metabolic homeostasis, particularly in glucose utilization, insulin signalling, and lipid metabolism. This is especially relevant in conditions such as brain insulin resistance and neurodegeneration linked to metabolic syndrome, where disturbances in mitochondrial function and energy metabolism may also contribute to disease progression. This review synthesizes current findings on the shared and independent roles of vitamins D and K in glioma biology, neurodegenerative processes, and brain-related metabolic disorders. It further explores their therapeutic potential as adjunctive strategies in precision medicine, while identifying key gaps for future translational research. However, current evidence remains insufficient to establish either vitamin as a disease-modifying therapy.

Background/Objectives: AP-2 transcription factors are increasingly recognized as key regulators in cancer biology. The TFAP2E gene, which encodes the AP-2ε transcription factor, remains understudied in cancer compared with other AP-2 family members. The scarcity of studies examining potential AP-2ε targets and related genes limits our understanding of its functional significance. Moreover, related studies have not incorporated a screening step to select the tumor type for justified molecular investigation. Through comparison of tumor–normal expression differences in a pan-cancer spectrum, this study prioritized ovarian serous carcinoma for downstream assessment. Methods: Expression patterns were evaluated using GENT2, GEPIA2, and TNMplot. After prioritizing ovarian serous carcinoma, TFAP2E and related signatures in TCGA-OV were analyzed using transcriptomic and clinical data from GDC and CDR, followed by comparison of findings with the GSE32062 cohort. The workflow included survival and clinicopathological analyses, outcome-independent limma-voom differential expression analysis and WGCNA, MCODE clustering, gene ontology, immune subtype and stemness assessment, PCA, CancerHallmarks enrichment, clinically adjusted Cox and competing-risk survival modeling, and HPA-derived immunostaining evaluation. Additional analyses assessed WGCNA parameter stability and preservation in GSE32062, an outcome-independent MAD-based variability screen, AP-2 family coexpression, and promoter motif enrichment. Results: TFAP2E was downregulated in ovarian cancer across the three queried resources, whereas higher expression was associated with favorable survival across multiple endpoints. Differential expression and WGCNA identified a TFAP2E-associated signature; its ontology indicated GPCR, stimulus responsiveness, and KRAS enrichment for the 933-gene module. The WGCNA pink module was stable across alternative settings, moderately preserved in GSE32062 (Zsummary = 7.86), and enriched in the outcome-independent MAD screening. GSE32062 supported concordant gene expression patterns and showed an association of TFAP2E with progression-free survival. Exploratory immune analyses showed a modestly increased proportion of C5 tumors in the higher-expression groups, whereas differences in stemness were statistically insignificant. The TFAP2E group associations with PFI and DSS in TCGA-OV and with PFS in GSE32062 remained significant after clinical adjustment; Fine-Gray sensitivity analyses gave consistent results for DSS. Immunohistochemistry provided protein-level characterization; eighteen entries differed between representative normal and tumor specimens, with lower tumor staining in fifteen. The seven-gene candidate set showed a clinically adjusted DSS association in TCGA-OV, which was not supported in the GSE32062 evaluation model. Conclusions: TFAP2E expression is associated with survival and a transcriptomic cross-cohort pattern in ovarian serous carcinoma. Covariate-adjusted and competing-risk analyses supported the association but did not establish clinical utility. The highlighted genes remain exploratory candidates for mechanistic investigation.

Background/Objectives: AP-2δ, encoded by TFAP2D, is one of the least characterized members of the AP-2 transcription factor family, although available evidence suggests biologically relevant roles in lung cancer that have not yet been thoroughly examined. The aim of the present study was to provide an integrated characterization of AP-2δ/TFAP2D in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Methods: LUAD and LUSC data were obtained from The Cancer Genome Atlas. The analysis comprised the expression profiling of AP-2δ target genes, survival-guided TFAP2D stratification, clinical profiling, differential expression and intersection analyses, methylation-derived chromatin compartment profiling, TFAP2D-associated cofactor rewiring, and genome-wide enrichment of AP-2δ targets. In parallel, pocket prioritization was performed using an AlphaFold model of AP-2δ with cross-tool consensus mapping. Results: TFAP2D stratification delineated biologically-distinct states in both histological subtypes (LUAD and LUSC). AP-2δ target genes showed subtype-specific expression patterns and functional organization. The consistent survival association was observed for progression-free interval rather than uniformly across all endpoints. Clinical profiling was more closely associated with molecular subtype composition than broad clinicopathological differences. Differential expression analyses identified both shared and histology-dependent programs associated with TFAP2D. In the chromatin-compartment analysis, LUSC showed a broader and more coherent footprint, whereas LUAD displayed more selective cofactor rewiring. Structure-based analysis prioritized a small set of reproducible candidate pockets concentrated within ordered regions of the TF_AP-2 domain. Conclusions: AP-2δ marks biologically meaningful but histologically non-uniform regulatory states in lung cancer. These findings provide an integrated framework for understanding TFAP2D-dependent regulation in LUAD and LUSC, highlighting AP-2δ as a candidate for future mechanistic and translational investigation.

Ferroptosis is an iron-dependent programmed cell death (PCD) implicated in cancer therapy response, yet its transcriptional control remains unevenly characterized and often centered on a limited subset of transcription factors (TFs) rather than systematically addressing TF families. The Activating enhancer-binding Protein-2 (AP-2) family of TFs is a plausible but understudied regulatory node linking oncogenic programs to ferroptosis, with prior research limited to AP-2α and AP-2γ, suggesting anti-ferroptotic and pro-tumorigenic roles. Thus, the present study aimed to provide a family-wide analysis of the relationships between AP-2 and ferroptosis across tumors in which this PCD type is considered biologically and clinically relevant. The research integrates ferroptosis gene modules with AP-2 targetomes, tumor–normal expression comparisons, survival stratification, ferroptosis scoring, cross-cohort functional analyses, and signaling pathway projection extending canonical ferroptosis circuits with AP-2–associated non-canonical elements. Consistent associations between AP-2 expression, prognosis, and ferroptosis score were observed in five tumor cohorts: cervical squamous cell carcinoma, glioblastoma, ovarian serous cystadenocarcinoma, pancreatic adenocarcinoma, and thyroid carcinoma. In addition, cross-cohort clustering highlighted genes enriched in redox- and lipid-metabolism programs linked to apoptosis and autophagy-dependent death. Among the candidates emerging from these analyses, ferroptotic markers (LOX, PTGS2, and NQO1) and AP-2–linked nodes such as CD36, DUOX1, EPHA2, MUC1, PTPRC, SNAI2, and TP63 warrant targeted functional and binding validation to infer whether these associations reflect direct AP-2 regulatory mechanisms. Most importantly, AP-2–centered research appears to be a valuable area for guiding studies of tumor-specific ferroptosis vulnerability or resistance.

The AP-2 family is a group of key regulators in cancer, yet their relationship with intratumoral microbes remains undefined. The present pan-cancer workflow leveraged TCGA transcriptomic data to correlate expression of AP-2 representatives with bacterial abundance on the genus and species level, followed by cohort-specific survival modeling, clinical profiling, differential expression, weighted co-expression analysis, and chromatin proximity tests with AP-2 enrichment. Significant correlations between microbiota and AP-2 were observed in 18 of 33 analyzed tumor types; TFAP2E-AS1 was most recurrent among AP-2 members, and Halomonas was most recurrent among genera. Further species-level verification and prognostic importance nominated three promising pairs: Paraburkholderia fungorum–TFAP2E in adrenocortical carcinoma (ACC), Actinomyces oris–TFAP2E in diffuse large B-cell lymphoma (DLBC), and Cutibacterium granulosum–TFAP2B in stomach adenocarcinoma (STAD). An attempt to define a consensus expression signature driven by microbiota and AP-2, yet independent of the specific species or family member, revealed genes regulating various biological processes and pathways. ACC and DLBC shared a consensus expression program, whereas STAD diverged; chromatin analysis showed AP-2 motifs near microbe-responsive genes in ACC and DLBC but not STAD, supporting cohort-specific regulation. Collectively, AP-2 family members emerge as plausible mediators of tumor microbiota–host interplay, warranting further mechanistic and translational research.

Climate change presents significant global challenges, with rising temperatures, extreme weather events, and degrading ecosystems threatening both human societies and the environment. The increasing intensity of these climatic effects demands innovative approaches to adaptation and mitigation. Hydrogels, three-dimensional networks of crosslinked polymers with water absorption and retention properties, have become viable multipurpose materials for climate solutions in response to these pressing issues. This review examines four primary applications of hydrogels as climate technologies: atmospheric water harvesting, passive cooling, soil health enhancement, and energy conservation. These materials address climate challenges through their unique properties including high water absorption capacity, stimuli-responsive behavior, and biocompatibility. By effectively capturing moisture, hydrogel-based devices provide sustainable freshwater production in areas with limited water resources. For thermal management, they offer passive cooling through evaporative processes, reducing energy consumption compared to conventional air conditioning systems. Superabsorbent hydrogels in agriculture help drought-resistant crop development in arid areas and improve soil water retention. Smart windows with thermochromic hydrogels allow for passive energy savings by dynamically modulating the sun’s light without the need for additional electricity. Through integrated deployment techniques, biodegradable formulations from sustainable sources handle various climate issues while ensuring environmental compatibility.

The aim of this study was to investigate the prognostic and predictive properties of four specific genes in triple-negative breast cancer (TNBC). We focused on ADIPOQ, GAS5, GATA4, and YAP1, which are known for their roles in key molecular pathways related to tumorigenesis, such as adipokine signaling, lncRNA regulation, transcriptional control, and Hippo signaling, but have not been sufficiently explored in the context of epigenetic regulation in breast cancer. Using the methylospecific PCR (MSP) method, we analyzed the methylation of the four genes in the tumor tissues collected from 57 TNBC patients. We evaluated their association with response to neoadjuvant treatment and clinicopathological characteristics. Additionally, we performed a bioinformatic analysis of methylation and expression data from The Cancer Genome Atlas (TCGA) TNBC cohort to explore their relationships with overall survival (OS), disease-specific survival (DSS), disease-free interval (DFI), progression-free interval (PFI), and relapse-free survival (RFS). No significant associations were observed between methylation patterns and clinicopathological characteristics in the patients. However, in silico analysis of the TNBC cohort identified ADIPOQ methylation as having the most significant associations, correlating with all five survival endpoints, including OS, DSS, DFI, PFI, and RFS. GAS5 methylation was significantly associated with OS, DSS, and RFS, and GATA4 methylation showed significant associations with PFI, whereas YAP1 methylation was significantly associated with OS and RFS. In addition, GAS5 expression was linked to DSS, DFI and RFS. This study highlights the potential prognostic significance of the epigenetic regulation of ADIPOQ in TNBC. The in silico findings shed light on the molecular pathways associated with TNBC progression and warrant further investigation to validate their role in clinical outcomes and underlying biological mechanisms.

This comprehensive review examines the therapeutic potential of metformin, a well-established diabetes medication, in treating neurodegenerative disorders. Originally used as a first-line treatment for type 2 diabetes, recent studies have begun investigating metformin’s effects beyond metabolic disorders, particularly its neuroprotective capabilities against conditions like Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, and multiple sclerosis. Key findings demonstrate that metformin’s neuroprotective effects operate through multiple pathways: AMPK activation enhancing cellular energy metabolism and autophagy; upregulation of antioxidant defenses; suppression of inflammation; inhibition of protein aggregation; and improvement of mitochondrial function. These mechanisms collectively address common pathological features in neurodegeneration and neuroinflammation, including oxidative stress, protein accumulation, and mitochondrial dysfunction. Clinical and preclinical evidence supporting metformin’s association with improved cognitive performance, reduced risk of dementia, and modulation of pathological hallmarks of neurodegenerative diseases is critically evaluated. While metformin shows promise as a therapeutic agent, this review emphasizes the need for further investigation to fully understand its mechanisms and optimal therapeutic applications in neurodegenerative diseases.