Search Results (35,367)

Psoriasis vulgaris is a T-cell-mediated skin disease that may involve an autoimmune response against melanocytes. It develops through still unexplained pathomechanisms. Streptococcal tonsillopharyngitis is a major trigger of psoriasis onset and relapses. HLA-C*06:02 is the main psoriasis risk gene. Here we find that B cells isolated from streptococci-infected tonsils or peripheral blood of HLA-C*06:02⁺ psoriasis patients stimulate an HLA-C*06:02-restricted melanocyte-reactive Vα3S1/Vβ13S1 T-cell receptor (TCR) from a lesional psoriatic CD8⁺ T cell clone in an IFN-γ-enhanced manner. Patients’ B cells furthermore induce proliferation of autologous blood CD8⁺ T cells. We identify several HLA-C*06:02-presented self-peptides in the immunopeptidomes we had isolated from four HLA-C*06:02 homozygous B-cell lines that stimulate the Vα3S1/Vβ13S1 TCR and differ from the melanocyte autoantigen recognized by this TCR. These data suggest that the proinflammatory environment of streptococcal tonsillopharyngitis may enable B cells to activate autoreactive CD8⁺ T cells that, owing to the polyspecificity of T-cell receptors, recognize several B-cell self-peptides presented by HLA-C*06:02 and subsequently cross-react against melanocytes in the skin, thereby triggering psoriasis. The capacity of B cells to stimulate a cross-reactive autoimmune response through HLA class I-presented B-cell peptides is a previously unknown mechanism in the induction of autoimmunity that could explain psoriasis onset and persistence. Full article

Managing bacterial infections and the spread of microbial resistance is one of the most critical and complex tasks of modern healthcare infrastructures. Antiseptics and disinfectants such as biocides play a significant role in controlling microbial resistance by reducing the microbial load on surfaces, skin, and environments, thereby limiting the opportunity for pathogens to proliferate and develop resistance. Herein, we tested the different interactions of quaternary ammonium compound (QAC)-based biocide compositions in pursuit of a better antimicrobial performance. An extensive microbiological analysis was conducted for 12 selected compositions of various combinations of mono-QACs, bis-QACs, and alcohols on 17 strains of bacteria of the ESKAPEE group and fungi, including 11 clinical highly resistant varieties, highlighting synergistic or additive dynamics. The evaluation showed noticeable improvements in activity, with up to 16-fold MBC and 32-fold MBEC reductions for alcohol-based compositions of lead QAC. Moreover, synergistic interactions were detected and confirmed via an optimized checkerboard assay for pyridinium QAC combinations against planktonic Gram-positive S. aureus with a fractional inhibitory concentration index (FICI) and fractional bactericidal concentration index (FBCI) of 0.39–0.5 and Gram-negative A. baumannii biofilms. The studied biocides demonstrated the long-term preservation of antimicrobial efficiency without resistance development during a 40-day period and do not induce QAC-associated cross-resistance for four commercially available antibiotics with similar mechanisms of action. Full article

Hyaluronic acid formulations are widely used in aesthetic and regenerative medicine, yet molecular weight-dependent effects on cellular repair remain incompletely characterized. This study investigated two hyaluronic acid formulations—low- and medium-high-molecular-weight ranges with trehalose (LMHMW-HA; 200–400 and 1200–1500 kDa) and high-molecular-weight range (HMW-HA; 1800–2600 kDa)—on keratinocyte repair using an in vitro scratch assay. Human keratinocyte monolayers were treated with various concentrations, and repair dynamics were monitored over 48 h through microscopy and quantitative inter-edge distance analysis. Both formulations significantly enhanced gap closure compared to controls without cytotoxic effects. LMHMW-HA promoted gradual closure over 48 h with increased cellular density, indicating sustained proliferation and migration. HMW-HA induced faster closure at approximately 30 h, accompanied by transient pericellular swelling consistent with hydration-mediated edge approximation. These findings indicate that LMHMW-HA and HMW-HA promote repair through distinct patterns: LMHMW-HA was associated with gradual closure and increased cellular density consistent with proliferation-driven repair, while HMW-HA induced rapid closure with transient pericellular swelling consistent with hydration-mediated effects. These preliminary observations suggest complementary repair mechanisms and provide a foundation for future mechanistic investigations. The molecular weight-tailored approach combining HA with trehalose offers therapeutic potential for aesthetic and regenerative medicine applications requiring enhanced tissue repair. Full article

Rheumatoid arthritis (RA) and osteoarthritis (OA) are significant global health challenges, fueling the need for innovative therapeutic strategies. Natural polyphenolic compounds, such as green tea catechins, exhibit promising anti-inflammatory, antioxidant, and immunomodulatory properties, making them potential adjuncts to rheumatic disease therapy. This review examines the effects of catechins, particularly epigallocatechin-3-gallate (EGCG), on key pathophysiological processes associated with RA and OA, such as pro-inflammatory cytokine production, oxidative stress, cartilage degradation, angiogenesis, and immune cell activation and proliferation. This study contains experimental data contained in full-text articles published in open-access indexed journals published only in English. The most important conclusions drawn from the in vitro and in vivo studies available so far, as well as studies on patients, show that green tea catechins modulate pro-inflammatory pathways, reduce the level of pro-inflammatory cytokines and improve the condition of the intercellular matrix in joint tissues, limiting the destruction of joint tissues in animals and patients and reducing pain. Although these studies suggest potential benefits, such as reduced inflammation and improved clinical parameters, the number and scale of studies are insufficient to confirm the clinical efficacy in a broad patient population. Therefore, claims of adjunctive therapy to conventional therapies should be interpreted with caution, and further well-designed and more powerful clinical trials are needed to verify the translation of the promising molecular mechanisms of green tea catechins into clinical practice. Full article

The role of Signal Transducer and Activator of Transcription 2 (STAT2) in cancer remains poorly understood. STAT2 is a key mediator of type I interferon (IFN) signaling, activating the expression of IFN-stimulated genes with antiviral and antiproliferative effects. However, emerging evidence suggests that STAT2 can also promote tumor growth. Here, we show that high STAT2 mRNA expression in colon cancer tumors correlates with reduced overall survival in patients. In preclinical models, deletion of STAT2 in tumor cells suppressed tumor growth, whereas STAT2 overexpression enhanced tumor growth, supporting its pro-tumorigenic role. To determine whether this function depends on type I IFN receptor (IFNAR1) signaling, we generated IFNAR1 knockout (IFNAR1 KO) colon carcinoma cells and compared their growth with parental and STAT2-deficient (STAT2 KO) tumor cells. Loss of type I IFN signaling was confirmed by western blot and qPCR analyses. In vitro, IFNAR1 KO and STAT2 KO tumor cells proliferated at similar rates. However, in xenograft tumor transplantation models, IFNAR1 KO cells formed larger tumors while STAT2 KO tumor cells formed smaller ones compared to parental tumor cells. These findings indicate that STAT2 promotes colorectal cancer growth through mechanisms independent of IFNAR1 signaling. Full article

Prostate adenocarcinoma is mainly diagnosed based on serum PSA levels, but elevated PSA levels can also be caused by BPH, which weakens its specificity. Recent scientific studies have demonstrated that specific microRNAs regulate cancer cell proliferation by modulating the Wnt/β-catenin pathway. To date, no published literature has provided a comprehensive assessment of the interactions between miR-106a-5p and miR-375-3p and components of the Wnt/β-catenin pathway in prostate cancer. Therefore, the aim of the present study was to perform a pilot evaluation of the expression of miRNAs 106a-5p and 375-3p, as well as β-catenin, Fzd8, Wnt5a, and cyclin D1 in prostate adenocarcinoma compared with BPH. The study material consisted of samples collected from 30 patients with prostate cancer and 30 with BPH. Protein expression was analyzed using IHC and qRT-PCR methods, while miRNA levels were quantified by dPCR. Our study results revealed lower immunoreactivity and expression of genes encoding β-catenin, Fzd8, Wnt5a, and cyclin D1 and significantly higher fluorescence intensity of miRNA 106a-5p and 375-3p with prostate adenocarcinoma compared to BPH. These parallel alterations in miRNA expression and Wnt/β-catenin-related components reflect disease-specific expression patterns and warrant further investigation in larger cohorts to determine their potential utility as diagnostic biomarkers in prostate diseases. Full article

Huanghuai sheep, a newly developed meat-specialized breed in China, are valued for their rapid growth and high meat quality, but the optimal slaughter age and the molecular basis of these traits remain poorly understood. Gaining insight into these mechanisms is vital for improving production efficiency and guiding molecular breeding in this economically important breed. Although previous studies have described the phenotypic characteristics of Huanghuai sheep, the genetic regulatory networks controlling muscle growth and meat quality at different developmental stages remain unclear. No thorough analysis of growth traits and transcriptomic variations across key age points has been conducted. Therefore, in this study, we aimed to evaluate how growth stage influences muscle development, carcass characteristics, and meat quality in Huanghuai sheep by integrating phenotypic characterization with transcriptomic profiling to identify key genes and molecular pathways underlying these economically important traits throughout development. Sixty Huanghuai sheep were assigned to three groups (twenty per group) representing key developmental stages (3, 9, and 18 months of age). Carcass traits and meat quality were evaluated. RNA sequencing of the longissimus dorsi muscle was performed to identify differentially expressed genes (DEGs), followed by bioinformatics analysis and experimental validation. The results indicated that the 9-month-old sheep presented a favorable balance of dressing percentage and intramuscular unsaturated fatty acid content, while those aged 18 months old exhibited the highest dressing percentage (61.23%). Transcriptome analysis identified 1395 DEGs (p < 0.05 and |log2FC| > 1) and enrichment analysis revealed key pathways involved in thyroid hormone synthesis, skeletal muscle satellite cell proliferation, and skeletal muscle tissue growth. Several candidate genes for muscle development (e.g., ACTC1, SIX2, HK2) and meat quality (e.g., TLR2, CHI3L1, ACOT7) were identified and validated. Their expression patterns showed significant correlations between critical growth performance and fatty acid composition metrics. These findings provide novel insights into the molecular networks regulating economically important traits in Huanghuai sheep, offering valuable targets for future molecular breeding programs aimed at enhancing productivity and meat quality. Full article

Histone deacetylases (HDACs) are pivotal epigenetic regulators that control gene expression, cell proliferation, and differentiation, and their dysregulation is closely associated with the onset and progression of multiple cancers. The therapeutic importance of these enzymes is reflected by FDA approval of HDAC inhibitors for oncology indications. Despite this clinical success, most FDA-approved agents employ conventional zinc-binding groups (ZBGs) such as hydroxamic acid and 2-aminoanilide, which are frequently linked to metabolic instability, genotoxicity, and poor pharmacokinetic behavior. These limitations have spurred the development of structurally diverse and safer HDAC inhibitors incorporating alternative ZBGs. This review provides a comprehensive analysis of recently developed HDAC inhibitors reported in the last few years, emphasizing their structure–activity relationships (SARs), chemical scaffolds, and binding features—including cap, linker, and ZBG motifs. Both hydroxamate-based and non-hydroxamate inhibitors, such as benzamides, hydrazides, and thiol-containing analogs, are critically evaluated. Moreover, the potency and selectivity profiles of these inhibitors are summarized across different cancer and normal cell lines, as well as specific HDAC isoforms, providing a clearer understanding of their therapeutic potential. Emerging dual-target HDAC inhibitors, such as HDAC–tubulin, HDAC–PI3K and HDAC–CDK hybrids, are also discussed for their synergistic anticancer effects. Full article

Background/Objectives: Colorectal cancer (CRC) is one of the most aggressive malignancies and has a very high mortality rate. Several studies have shown that obesity and hyperlipidemia are among the factors implicated in the onset of this disease. These factors can be modified through lifestyle changes, and diet plays a crucial role in this context. We evaluated the effects of Tuber borchii (T. borchii) fungal extracts based on experimental evidence showing that some truffles produce antioxidant, anti-inflammatory, and anticancer secondary metabolites. Methods: To this end, we treated human colorectal cancer cells (HCT 116) with various extracts of T. borchii at different time points and concentrations. Results and Conclusions: The results showed that the treatments caused a decrease in cell proliferation due to the induction of apoptotic cell death, as evidenced by FACS analyses. The apoptotic pathway was confirmed by the increase in the cleavage of Caspase 3 and Caspase 9. We then investigated the molecular mechanisms underlying cell death, finding increased nuclear localization of p53 and increased expression of its downstream pro-apoptotic genes, PUMA and NOXA. Among the upstream signaling events, we identify an increase in p-ERK1/2, a MAPK member involved in several antiproliferative/pro-apoptotic insults. Full article

The widespread use of anticancer drugs (ACDs) in human therapies determines the occurrence of these potent cytotoxic chemicals into aquatic ecosystems. Nowadays, ACDs are ubiquitous contaminants in wastewater effluents and freshwater compartments, raising urgent questions about their environmental impact. Designed to disrupt cellular proliferation, these compounds are inherently bioactive and can exert toxic effects on non-target organisms even at trace concentrations. Conventional fate and toxicity tests provide important initial data but are limited in ecological realism, often focusing on single-specie and single-endpoint under controlled conditions and overlooking complex interactions, trophic dynamics, and long-term chronic exposures. Knowledge of all these aspects is needed for proper monitoring, assessment, and regulation of ACDs. Simulated ecosystem experiments, such as mesocosms, provide intermediate-scale, semi-controlled platforms for investigating real-world exposure scenarios, assessing ACD fate, and identifying both direct and indirect ecological effects. They offer distinct advantages for evaluating the chronic toxicity of persistent pollutants by enabling realistic long-term contamination simulations and supporting the simultaneous collection of comprehensive hazard and exposure endpoints. This perspective underscores the growing concern surrounding the contamination of ACDs, examines the limitations of traditional assessment approaches, and advocates for mesocosm-based studies as a critical bridge between laboratory research and ecosystem-level understanding. By integrating mesocosm experiments into environmental fate and risk evaluation, we can better predict the behavior and ecological consequences of anticancer pharmaceuticals, guiding strategies to mitigate their impact on aquatic life. Full article

Background: Fluid shear stress (FSS) is a biomechanical force that can produce phenotypic changes in the cells that are directly in contact with the flow of fluid. Accumulating evidence indicates high FSS to possess the potential ability to prevent tumor development and suppress cancer growth. However, the exact mechanism of its antitumorigenic effects is still not clear. Objective: In this study, we aimed to investigate the effect of FSS on breast cancer microenvironment via macrophage modulation. Methods: We exposed THP-1 like-macrophages to different levels of FSS. The supernatant from THP1-like-macrophages after exposure to FSS was used as conditioned medium (FSS-CM). Subsequently, we analyzed human breast cancer cells, MCF-7, and endothelial cells, as well as HUVECs cultured with FSS-CM. Results: Study outcomes have demonstrated that low FSS-CM inhibited apoptosis as well as induced tumor migration in MCF-7 cells. Conversely, high FSS-CM promoted apoptosis, inhibited tumor migration, and induced G1-phase arrest in MCF-7 cells. Furthermore, low FSS-CM was found to promote proliferation of HUVECs. Conclusions: In conclusion, this study highlights the complex interplay between FSS and cancer cell behavior. Our findings provide in vitro evidence that high FSS exerts an anti-cancer effect by promoting THP-1-like macrophage polarization toward an anti-tumor phenotype, leading to increased apoptosis and reduced migration in MCF-7 cells. These results suggest that the modulation of macrophage polarization may underlie the therapeutic potential of high FSS in suppressing breast cancer progression. Full article

CD36, a fatty acid scavenger receptor expressed in tumors, is associated with a poor prognosis in several cancers. Our previous research demonstrated the involvement of CD36 in the proliferation and migration of oral squamous cell carcinoma (OSCC) cells. However, the clinical significance of CD36 expression in OSCC remains unclear. The purpose of this study was to evaluate the association between CD36 expression and the clinicopathological characteristics of OSCC patients. Immunohistochemical expression of CD36 was quantified using the H-score, and its association with clinicopathological characteristics was evaluated in 55 OSCC patients. The mean H-score for membrane-associated CD36 expression was 84.8. CD36 expression was significantly correlated with tumor stage, mode of invasion, differentiation, and recurrence of OSCC cells. Moreover, elevated CD36 expression was significantly correlated with a high rate of relapse. Univariate and multivariate analyses showed that CD36 expression was an independent risk factor for relapse. Moreover, The Cancer Genome Atlas (TCGA) dataset analysis revealed that CD36 expression may coexist with transcriptional activation of β-oxidation-related and epithelial–mesenchymal transition (EMT)-related pathways. These findings suggest that CD36 might serve as a predictive biomarker for OSCC malignancy and recurrence. Full article

The proliferation of Unmanned Aerial Vehicles (UAVs) enables the large-scale collection of ecological data, yet translating this dynamic sensor data into engaging, personalized public experiences remains a significant challenge. Existing solutions fall short: static exhibitions lack adaptability, while general-purpose LLM agents struggle with real-time responsiveness and reliability. To address this, we introduce CurationAgent, a novel intelligent agent built upon the State-Gated Agent Architecture (SGAA). Its core innovation is an advanced hybrid curation pipeline that synergizes Retrieval-Augmented Generation (RAG) for broad semantic recall with an Intent-Driven Curation (IDC) Funnel for precise intent formalization and narrative synthesis. This hybrid model robustly translates user intent into a curated, multi-modal narrative. We validate this framework in a proof-of-concept virtual exhibition of the Lalu Wetland’s biodiversity. Our comprehensive evaluation demonstrates that CurationAgent is significantly more responsive (1512 ms vs. 4301 ms), reliable (95% vs. 57% task success), and precise (85.5% vs. 52.7% query precision) than standard agent architectures. Furthermore, a user study with 27 participants confirmed our system leads to measurably higher user engagement. This work contributes a robust and responsive agent architecture that validates a new paradigm for interactive systems, shifting from passive information retrieval to active, partnered experience curation. Full article

Background: Cultured human skin explants provide preclinical models to investigate drug delivery and the efficacy of topical treatments for wound healing. However, different culture conditions may affect cell viability, proliferation, and even wound healing. Since animal-derived supplements can influence the investigation of human physiological responses, this study evaluated the effects of non-animal supplements on the ex vivo wound healing process to improve the use of this model for preclinical drug efficacy tests. Methods: In in vitro scratch assays using HaCaT cells and fibroblasts, for media supplemented with normal human serum (NHS), oxygen carriers (OCs) had a positive impact on cell migration, supporting the further evaluation in ex vivo skin culture models. Human skin explants with standardized superficial wounds were cultured in four supplemented media: (i) Dulbecco’s Modified Eagle Medium High Glucose (DMEM) with fetal calf serum (FCS), (ii) DMEM with NHS and OC, (iii) CnT-Prime^TM with NHS and OC, and (iv) EpiLife™ with NHS and an OC. Results: During the 12-day culture, we observed re-epithelialization in all groups with the exception of EpiLife + NHS + OC (with no Ca⁺⁺ supplement). For these samples, starting from day 6, we noticed a loosening of the dermal–epidermal junction and disruption of the upper epidermal layer. Furthermore, an immunohistochemical analysis of extracellular matrix components and remodeling factors, including type I and III collagen, transforming growth factor-β2, and matrix metalloproteinase-9, provided insights into tissue repair dynamics. Conclusions: NHS plus OC is comparable to FCS supplementation and represents a more physiological and ethical alternative. Full article

Objectives: Small cell lung cancer (SCLC) is an aggressive neuroendocrine carcinoma characterized by rapid proliferation, early metastasis, and limited therapeutic response. Metabolic reprogramming is increasingly recognized as a key feature of small cell lung cancer progression, yet the contribution of specific metabolic enzymes remains incompletely understood. This study aimed to investigate the role of asparagine synthetase in small cell lung cancer tumorigenicity and disease progression. Methods: Integrative analyses were performed using public transcriptomic datasets, proteomic profiling, and functional assays in vitro and in vivo. Asparagine synthetase expression levels were evaluated in normal lung, non-small cell lung cancer, and small cell lung cancer tissues using public microarray datasets. Loss of function studies were conducted using shRNA mediated knockdown in murine and human small cell lung cancer cell models. Tumor growth and survival were assessed using xenograft mouse models. Results: Asparagine synthetase expression was significantly elevated in small cell lung cancer compared with normal lung and non-small cell lung cancer tissues. Genetic depletion of asparagine synthetase impaired cellular proliferation and colony forming capacity in vitro. In vivo, asparagine synthetase knockdown suppressed tumor growth and was associated with prolonged survival in xenograft mouse models. Conclusions: These findings demonstrate that asparagine synthetase contributes to tumor growth and metabolic adaptability in small cell lung cancer. The results support a functional role for asparagine synthetase in malignant progression and suggest that targeting asparagine metabolism may represent a potential therapeutic approach in aggressive small cell lung cancer. Full article