Search Results (576)

Objective: Previous reports showed that periodontopathic bacteria induce epithelial–mesenchymal transition (EMT) in oral squamous cell carcinoma (OSCC). Fisetin, a foodborne flavonoid, is reportedly associated with anticancer potential in various carcinogenic processes. This study aimed to elucidate the effects of fisetin on Fusobacterium nucleatum- and Porphyromonas gingivalis-induced EMT in OSCC cells. Methods: OSCC cells were co-cultured with live and heat-killed forms of F. nucleatum and P. gingivalis. The concentration of fisetin was set at 10 μM. Morphological changes in the OSCC cells were observed under a light microscope. Cell viability was measured using the Cell Counting Kit-8 assay, whereas migration was examined via wound healing. The mRNA expression of EMT-related markers was quantified using quantitative real-time polymerase chain reaction (PCR), and the expression of EMT-related markers and Wnt pathway-associated proteins was examined via Western blotting. Results: At a multiplicity of infection (MOI) of 300:1 for F. nucleatum and 100:1 for P. gingivalis, OSCC cell viability remained unchanged; however, wound closure rates increased significantly relative to the control. Likewise, treatment with fisetin (10 µM) did not materially alter viability; nevertheless, it attenuated promigratory effects induced by heat-killed periodontal pathogens at 3 h and 6 h. The OSCC cells exhibited EMT-like morphological changes after 6 h of co-culture with heat-killed pathogens. Consistently, reverse-transcriptase quantitative PCR and Western blot analyses showed increased expression of TWIST, ZEB1, and N-cadherin, accompanied by decreased E-cadherin expression, which was more pronounced in F. nucleatum than in P. gingivalis. However, fisetin reversed these trends. Moreover, co-culture with heat-killed pathogens markedly elevated β-catenin protein levels. In line with modulation of canonical Wnt/β-catenin signaling, fisetin and a Wnt inhibitor reduced β-catenin expression, whereas co-treatment with a Wnt agonist restored β-catenin levels in the presence of fisetin. Conclusions: Heat-killed F. nucleatum and P. gingivalis induced EMT in OSCC cells, with F. nucleatum exerting the strongest effect. Fisetin suppressed pathogen-driven EMT, at least partly via canonical Wnt/β-catenin signaling, highlighting its potential therapeutic value and warranting further investigation. Full article

Adenomyosis (AM) is a hormonally responsive uterine disorder defined by ectopic endometrial tissue within the myometrium, causing pain, abnormal bleeding, and subfertility. Non-coding RNAs (ncRNAs)—including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs)—are post-transcriptional regulators implicated also in uterine remodeling. We systematically reviewed original studies evaluating ncRNAs in AM using human samples, in vitro and animal models, or bioinformatic approaches. Data sources included PubMed and Google Scholar (inception up to 10 August 2025). Forty-one studies were included and synthesized across mechanistic, diagnostic, and translational domains. miRNAs (n = 31) were the most studied subclass, followed by lncRNAs (n = 10) and circRNAs (n = 5). Recurrent miRNAs such as miR-10b and miR-30c-5p (downregulated, inhibitory) and miR-145 (upregulated, promotive) regulate epithelial invasion, epithelial–mesenchymal transition, and cytoskeletal remodeling via PI3K–AKT/MAPK and Talin1 signaling. The let-7a/LIN28B axis governed estrogen-sensitive proliferation in the junctional zone, while miR-21 exhibited compartment-specific roles in decidualization and ectopic cell survival. Extracellular-vesicle (EV)-bornemiRNAs (e.g., miR-92a-3p, miR-25-3p, miR-4669) contributed to immune polarization and show early diagnostic potential. lncRNAs and circRNAs acted via chromatin modifiers and ceRNA networks. Most findings remain at the discovery stage. Convergent dysregulation was observed in key signaling pathways, including JAK–STAT, Wnt/β-catenin, and Hippo–YAP. ncRNAs regulate critical axes of invasion, proliferation, immune modulation, and hormonal response in AM. Targets with preliminary causal support—miR-10b/ZEB1, let-7a/LIN28B, and miR-145/Talin1—warrant further validation. Circulating miRNAs—especially in EVs—offer promise for non-invasive diagnosis. Full article

Background/Objectives: TREM2 is a transmembrane receptor highly expressed in microglia and macrophages, and its involvement in Alzheimer’s disease, obesity, and cancer has garnered significant attention. Although its biological function has been actively investigated, the mechanisms by which its expression is regulated remain incompletely characterized. In this study, we aimed to identify transcription factors that modulate TREM2 expression among those reported to be expressed in microglia. Methods: We inserted a 5 kb upstream region of TREM2 into a luciferase reporter vector. This construct was co-expressed with 15 transcription factors, and the TREM2 transcriptional activity was evaluated using luciferase assays. The most promising transcription factor was subsequently knocked down in HMC3 cells, which are derived from human microglia, to assess its effect on endogenous TREM2 expression. Results: Among the 15 transcription factor candidates tested, SPI1 (PU.1), MAFB, CEBPA, ZEB2, and SALL1 most strongly enhanced TREM2 transcriptional activity. ZEB2 was prioritized due to its limited study in microglia and higher co-expression with TREM2. In HMC3 cells, ZEB2 knockdown reduced both TREM2 mRNA and protein levels. Further analysis using domain-deleted mutants of ZEB2 indicated that the zinc finger domains are essential for its transcriptional activity. Analysis using truncated mutants of the TREM2 upstream region suggests that ZEB2 acts on multiple sites within this region. Chromatin immunoprecipitation also suggested an interaction between ZEB2 and the upstream region of TREM2. Conclusions: This study novelly suggests ZEB2 as a transcription factor that promotes TREM2 expression. Further investigation into the role of ZEB2 in various TREM2-associated diseases is warranted. Full article

Non-small-cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide, demanding improved biomarkers and therapeutic approaches. This review synthesizes the extensive evidence positioning the miR-200 family as a master regulator of NSCLC progression. We detail the core molecular circuitry centered on the bistable, double-negative feedback loop between miR-200 and the ZEB1/ZEB2 transcription factors, which governs epithelial–mesenchymal transition (EMT). This review connects this central mechanism to critical clinical challenges, including the development of resistance to EGFR-targeted therapies and the regulation of immune evasion through PD-L1 expression and CD8+ T cell infiltration. We evaluate the strong clinical evidence for the miR-200 family’s utility as a diagnostic, prognostic, and predictive biomarker. Finally, we explore emerging therapeutic strategies that target this network, including miRNA replacement, epigenetic reactivation, and rational combinations with immunotherapy and targeted agents. We synthesize evidence positioning the miR-200/ZEB feedback circuit as a central regulatory node in NSCLC that links EMT with therapeutic resistance and immune evasion. Beyond summarizing associations, we interpret how this circuitry could inform biomarker development and rational combinations with targeted and immune therapies. Given heterogeneous study designs and non-standardized assays, translational claims remain provisional; we outline immediate priorities for assay harmonization and biomarker-stratified trials. Full article

In recent years, European and national policies on energy efficiency and sustainable construction have promoted a profound rethinking of building practices and strategies for upgrading the existing building stock. With the conversion of Law Decree No. 34 of 19 May 2020 (Decreto Rilancio) into Law No. 77 of 17 July 2020, and of Law Decree No. 76 of 16 July 2020 (Decreto Semplificazioni) into Law No. 120 of 11 September 2020, the tax deduction rate was increased to 110% for expenses related to specific interventions such as seismic risk reduction, energy retrofit, installation of photovoltaic systems, and charging infrastructures for electric vehicles in buildings—commonly known as the Superbonus 110%. Furthermore, the category of “building renovation,” as defined in Presidential Decree No. 380 of 6 June 2001 (art. 3, paragraph 1, letter d), was expanded with specific reference to demolition and reconstruction of existing buildings, allowing—under certain conditions—interventions that do not comply with the original footprint, façades, site layout, volumetric features, or typological characteristics. These measures were designed not only to positively affect household investment levels, thereby significantly contributing to national income growth, but also to support the broader objective of decarbonising the building sector while improving seismic safety. Within this regulatory and policy framework, instruments such as the Superbonus 110% have acted as a driving force for the diffusion of renovation projects aimed at enhancing energy performance and reducing greenhouse gas emissions, in line with the objectives of the European Green Deal and the Energy Performance of Buildings Directive (EPBD). This paper is situated within such a context and examines a real-world case of bio-based renovation admitted to fiscal incentives under the Superbonus 110%. The focus is placed on the procedural framework as well as on the technical, economic, and evaluative aspects, adopting a multidimensional perspective that combines regulatory, operational, and financial considerations. The case study concerns the demolition and reconstruction of a single-family residential chalet, designed according to near-Zero-Energy Building (nZEB) standards, located in the municipality of San Roberto, in the province of Reggio Calabria. The intervention is set within an environmentally and culturally sensitive area, being situated in the Aspromonte National Park and subject to landscape protection restrictions under Article 142 of Legislative Decree No. 42/2004. The aim of the study is to highlight, through the analysis of this case, both the opportunities and the challenges of applying the Superbonus 110% in protected contexts. By doing so, it seeks to contribute to the scientific debate on the interplay between incentive-based regulations, energy sustainability, and landscape–environmental protection requirements, while providing insights for academics, practitioners, and policymakers engaged in the ecological transition of the construction sector. Full article

Uveal melanoma (UM) is the most prevalent primary intraocular tumor in adults. Transcription factor ZEB1 is one of the potential master regulators of melanocytes plasticity, because it is recognized as a “driver” of epithelial-to-mesenchymal transitions (EMTs) in carcinomas. We studied the correlation of tumor invasiveness with ZEB1 status and vascular endothelial growth factor/its receptor (VEGF-A/VEGFR2) in UM cells, and also with melanocyte’s differentiation rate. Eight UM cell cultures were characterized by melanosomes content using an ETM. ZEB1, VEGF-A and VEGFR2 levels in UM cells were detected by RT-PCR, Western blot, ELISA and flow cytometry. Effects of siRNA-dependent ZEB1 knockdown on UM cell proliferation and their sensitivity to the VEGF-A inhibitor Eylea (aflibercept) were tested by MTT and in a real-time proliferation assay. UMs with an invasive growth type can maintain a high degree of melanocyte differentiation. All ZEB1^low cells were obtained from spindle cell tumors. The sensitivity of UM cells to Eylea inversely correlated with the level of the VEGFR2 receptor. ZEB1 knockdown completely blocked VEGF-A production while anti-VEGF treatment stimulated ZEB1 increase. In UM cell cultures, ZEB1 is a positive regulator of VEGF-A expression. In addition, there is probably a ZEB1 feedback loop that is sensitive to a drop in VEGF-A concentration. The data obtained allow us to consider ZEB1 silencing as an auxiliary link for a combined strategy of killing UM cells. Full article

Neuroinflammation is a key response to disturbed CNS homeostasis, largely mediated by activated microglia, and excessive microglia-driven inflammation can negatively impact neurogenesis. ZEB1 plays a crucial role in neurogenesis and brain development by influencing neural stem cell (NSC) maintenance, proliferation, and differentiation. This study aimed to evaluate how the knockdown of ZEB1 influences the behavior of NSCs in inflammatory environments. NSCs were isolated from the subventricular zone of rats, and ZEB1 knockdown was achieved using ZEB1 siRNA. A conditioned medium derived from lipopolysaccharide-activated microglia was utilized to induce inflammatory responses in NSCs. The silencing of ZEB1 in NSCs significantly reduced the expression of ZEB1. Furthermore, ZEB1 knockdown in NSCs resulted in a significant decrease in neurosphere formation, cell migration ability, reactive oxygen species generation, and various cytokine levels under both non-inflammatory and inflammatory conditions. These findings reveal the regulatory role of ZEB1 in the modulation of NSC behavior, suggesting that targeting ZEB1 may provide a potential therapeutic strategy for neuroinflammatory CNS disorders. Full article

The building sector plays a key role in the transition toward climate neutrality, with national regulations across the EU requiring the construction of nearly zero-energy buildings (nZEBs). However, while energy performance has been extensively studied, less attention has been given to the problem of ensuring user comfort—both indoors and in the surrounding outdoor areas—under nZEB design constraints. This gap raises two key research objectives: (1) to evaluate whether a well-designed nZEB with extensive glazing maintains acceptable indoor thermal comfort and (2) to assess whether residents experience greater outdoor thermal comfort and satisfaction in small, sun-exposed private gardens or in larger, shaded communal green spaces. To address these objectives, a newly built residential estate near Kraków (Poland) was analyzed. The investigation included simulation-based assessments during the design phase and in situ measurements during building operation, complemented by a user survey on spatial preferences. Indoor comfort was evaluated for rooms with large glazed façades, as well as rooms with standard-sized windows, while outdoor comfort was assessed in both private gardens and a shared green courtyard. Results show that shading the southwest-oriented glazed façade with an overhanging terrace provided slightly lower temperatures in ground-floor rooms compared to rooms with standard unshaded windows. Outdoors, users experienced lower thermal comfort in small, unshaded gardens than in the larger, vegetated communal area (pocket park), which demonstrated greater capacity for temperature moderation and thermal stress reduction. Survey responses further indicate that potential future residents prefer the inclusion of a shared green–blue infrastructure area, even at the expense of building some housing units in semi-detached form, instead of maximizing the number of detached units with unshaded individual gardens. These findings emphasize the importance of addressing both indoor and outdoor comfort in residential nZEB design, showing that technological efficiency must be complemented by user-centered design strategies. This integrated approach can improve the well-being of residents while supporting climate change adaptation in the built environment. Full article

Cellular plasticity enables cells to dynamically adapt their phenotype in response to environmental cues, a process central to development, tissue repair, and disease. Among the most studied plasticity programs is epithelial–mesenchymal transition (EMT), a transcriptionally controlled process by which epithelial cells acquire mesenchymal traits. Originally described in embryogenesis, EMT is now recognized as a key driver in both tumor progression and fibrotic remodeling. In cancer, EMT and hybrid epithelial/mesenchymal (E/M) states promote invasion, metastasis, stemness, therapy resistance, and immune evasion. In fibrotic diseases, partial EMT (pEMT) contributes to fibroblast activation and excessive extracellular matrix deposition, sustaining organ dysfunction mainly in the kidney, liver, lung, and heart. This review integrates recent findings on the molecular regulation of EMT, including signaling pathways (TGF-β, WNT, NOTCH, HIPPO), transcription factors (SNAIL, ZEB, TWIST), and regulatory layers involving microRNAs and epigenetic modifications. Moreover, we discuss the emergence of pEMT states as drivers of phenotypic plasticity, functional heterogeneity, and poor prognosis. By comparing EMT in cancer and fibrosis, we reveal shared mechanisms and disease-specific features, emphasizing the translational relevance of targeting EMT plasticity. Finally, we explore how cutting-edge technologies, such as single-cell transcriptomics and lineage tracing, are reshaping our understanding of EMT across pathological contexts. Full article

Background: A range of cancer cells are significantly inhibited by FTY720. It is unknown, nevertheless, how FTY720 influences the onset of non-small cell lung cancer (NSCLC). Using bioinformatics techniques, we analyzed and the possible molecular mechanisms and targets of FTY720 for the treatment of NSCLC. Methods: DEGs (Differentially expressed genes) were acquired by differential analysis of the dataset GSE10072. Obtained FTY720 target genes and NSCLC disease genes from databases such as Swiss-TargetPrediction and GeneCard. Subsequently, target and disease genes, as well as DEGs, were merged for Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, gene ontology (GO), and protein interaction analysis. The overlapping genes of DEGs and target genes, and disease genes were also obtained separately and subjected to survival as well as expression analyses. We constructed the regulatory network of miRNAs and transcription factors (TFs) on hub genes. Finally, the immune cell association of hub genes was evaluated using the ssGSEA method, molecular docking of FTY720 to hub genes was carried out utilizing Autodock, and molecular dynamics simulations were conducted. Results: In this study, 444 DEGs, 232 target genes of FTY720, and 466 disease genes were obtained. Moreover, a total of 1062 genes were obtained by removing duplicate values after merging, among which PIK3R1, Akt1, and S1PR1 had the highest DEGREE values in the protein interactions network, and these genes were primarily enriched in MAPK, PI3K-Akt signaling pathways, with the PI3K-Akt signaling pathway being the most prominent. Among the overlapping genes, three potential targets of FTY720 for NSCLC treatment were found: S1PR1, ZEB2, and HBEGF. ZEB2 and S1PR1 were determined to be hub genes and to significantly affect NSCLC prognosis by survival analysis. Furthermore, hsa-miR-132-3p, hsa-miR-192-5p, and hsa-miR-6845-3p were strongly associated with FTY720 for the treatment of NSCLC; CTBP1 (carboxy-terminal binding protein 1), EZH2 (protein lysine N-methyltransferase), and ZNF610 (zinc-finger protein 610) may all influence the expression of ZEB2 and S1PR1. Hub genes had a substantial negative link with memory B cells and a significant positive correlation with memory CD8 T cells and Th17 helper T cells. The molecular docking and kinetic simulation results of FTY720 with the two hub genes indicate that the protein-ligand complex has good stability. Conclusion: Our research indicates that FTY720 may inhibit NSCLC via possible targets ZEB2 and S1PR1, further laying the theoretical foundation for the utilization of FTY720 in NSCLC treatment. Full article

This article analyses the possibility of using Li-ion batteries removed from battery electric vehicles (BEVs) as short-term energy storage devices in a near-zero energy building (nZEB) in conjunction with a rooftop photovoltaic (PV) system. The technical and economic feasibility of this solution was compared to that of a standard commercial LIB (Lithium-Ion battery) BESS Battery Energy Storage System). Two generations of the same BEV model battery were tested to analyse their suitability for powering a building. The necessary changes to the setup of such a battery for building power supply purposes were analysed, as well as its suitability. As a result, analyses of profitability over the predicted life span and NPV (net present value) of SLEVBs (second-life BEV batteries) for building power were carried out. The study also conducted preliminary research on the effectiveness of such projects and their pros and cons in terms of security. The author calculates the profitability of a ready-made PV BESS with a set of SLEVBs, estimating the payback periods for such investments relative to electricity prices in Poland. The article concludes on the potential of SLEVBs to support self-consumption in nZEB buildings and its environmental impact on the European circular economy. Full article

Background: Breast cancer is a complex, multifactorial malignancy characterized by the uncontrolled proliferation of epithelial cells, with certain subtypes exhibiting resistance to conventional therapies. Plant-derived essential oils have been proposed as potential anticancer agents due to their bioactive compounds. Recent studies have demonstrated that Decatropis bicolor essential oil exhibits activity against breast cancer, attributed to diverse secondary metabolites such as δ-cadinene. Aberrant expression of adhesion and invasion proteins, including MMPs, CD44, N-cadherin, and ZEB-2, are key signs of breast cancer progression and metastasis; they represent relevant molecular targets. Objectives: To investigate the interaction of δ-cadinene with these proteins using in silico approaches and in vitro evaluations. Methods: In silico analyses were conducted to assess the interaction and stability of δ-cadinene with target proteins. In vitro assays, including cytotoxicity, morphological analysis, and cell invasion assays, were performed using MDA-MB-231 and MCF10-A cell lines. Results: Interaction analysis suggest that δ-cadinene interacts with key catalytic residues in MMP-2, sharing features with Quercetin. Blind docking revealed a second high-affinity site in the Fibronectin type II domain. Molecular dynamics simulations confirmed the stability of these complexes. In vitro studies showed that δ-cadinene significantly reduced MDA-MB-231 cell viability in a concentration-dependent manner, without affecting MCF10-A cells, and significantly inhibited invasion and MMP-2 activity after 24 h. Conclusions: δ-cadinene exhibits selective cytotoxic and anti-invasive activity in MDA-MB-231 cells, likely through dual inhibition of the catalytic and adhesion domains of MMP-2. These findings support δ-cadinene as a potential candidate for future therapeutic development in metastatic breast cancer. Full article

Background: Epithelial-mesenchymal transition (EMT) is prevalent in human cancer and facilitates tumor metastasis and therapy resistance by enhancing cancer cell motility, invasiveness, survival, and immune evasion. However, the molecular mechanisms underlying the cellular changes during EMT remain largely elusive, making it challenging to simultaneously target these diverse malignant phenotypes. Results: Here, we show that the EMT-inducing ZEB transcription factors directly repressed WWC1 (also known as KIBRA), a key upstream activating component of the Hippo signaling pathway. The EMT program thus inherently downregulated WWC1, leading to impaired Hippo signaling and constitutive activation of the downstream effector and transcriptional coactivator YAP. The YAP-dependent transcriptional program promotes manifold cellular phenotypes that resemble those induced during EMT. Indeed, pharmacological inhibition of YAP suppressed EMT-stimulated cell migration and invasion, apoptosis resistance, and cell size growth, identifying active YAP as a common essential mediator of multiple EMT-associated phenotypes. Moreover, YAP activation directly induced transcription of B7 family immune checkpoint proteins VSIR (VISTA) and PD-L2, and rendered cancer cells resistant to effector CD8 T cells. Conclusions: Collectively, the results suggest that EMT intrinsically activates YAP by repressing WWC1, providing a non-genetic mechanism for pervasive YAP activation in cancer. Activated YAP, in turn, critically contributes to diverse EMT-enhanced malignant phenotypes and immune evasion. Therefore, pharmacological targeting of YAP may suppress various EMT-associated malignant properties and improve the efficacy of anti-PD-1 immunotherapy, offering a promising therapeutic strategy against cancer cells exhibiting EMT characteristics. Full article

Cisplatin resistance remains a major therapeutic challenge in oral squamous cell carcinoma (OSCC), leading to treatment failure and poor outcomes. This study aimed to generate and characterize cisplatin-resistant OSCC models to elucidate resistance mechanisms. Two resistant OSCC cell lines (SCC-9R and HSC-3R) were developed through gradual dose escalation. Parental and resistant cells were analyzed via RNA-seq and gene set enrichment analysis, and validated through RT-qPCR, Western blot, immunofluorescence, and gelatin zymography. Functional assays, including 2D and 3D migration and invasion models, assessed phenotypic changes. A multi-omics analysis revealed molecular alterations in resistant cells, including 305 differentially expressed genes (DEGs) in HSC-3R (187 upregulated) and 782 in SCC-9R (298 upregulated) versus parental lines, with enrichment for extracellular matrix organization (p < 0.001) and consistent epithelial–mesenchymal transition (EMT) activation (p < 0.001), demonstrated by the upregulation of ZEB1, ZEB2, Vimentin, and TWIST1, and E-cadherin suppression. Functional validation confirmed an aggressive phenotype, including increased migration (p < 0.05), invasion (p < 0.01), and elevated MMP-2 (p < 0.01) and MMP-9 (p < 0.001) activity. Findings were verified in 3D spheroid models. Overall, cisplatin resistance in OSCC involves EMT, inflammatory signaling, and metabolic adaptation. The consistency of these features across both models supports the robustness of this in vitro system and reveals targets for therapeutic intervention. Full article

This study presents a simulation-based analysis of a steel modular building that integrates technologies that support the energy transition in the built environment. The focus is placed on the implementation of building-integrated photovoltaics (BIPVs), with photovoltaic modules incorporated into the façade and balcony railings. Several modern photovoltaic façade systems were examined. In addition, the study considers the application of photovoltaic glazing enhanced with active quantum coatings. Seven distinct BIPV modules were analysed, each characterised by unique features, with particular emphasis on the influence of colour in tinted variants. A performance degradation analysis was conducted for railing-mounted modules with varying glass tints. The simulation results were correlated with the building’s electricity demand. Full article