Search Results (2,194)

Background/Objectives: Cervical cancer treatment relies heavily on high-dose-rate (HDR) ¹⁹²Ir brachytherapy; however, therapeutic efficacy remains limited by tumor radioresistance and the inability to escalate dose without increasing toxicity to surrounding healthy tissues. The present study investigates the potential of gold nanoparticles (AuNPs) to enhance radiosensitivity under clinically relevant ¹⁹²Ir brachytherapy conditions through the combined action of physical dose amplification and radiobiological modulation. Particular emphasis is placed on the unique radiophysical interactions generated by the mixed gamma and secondary beta emissions of ¹⁹²Ir, which, in the presence of high atomic number nanoparticles, promote localized photoelectric absorption and the emission of low-range secondary electrons, including Auger electrons. The study further aims to determine how AuNPs size and post-irradiation temporal evolution influence radiation-induced cytotoxicity and apoptosis in cervical cancer cell lines, thereby providing a biologically representative model of nanoparticle-assisted brachytherapy. Methods: Clonogenic survival, dose enhancement factor (DEF), and apoptosis were evaluated following irradiation in the presence of 10 nm and 50 nm AuNPs in two independent biological experiments (n = 2). Results: A clear dose-dependent reduction in survival fraction and increase in apoptosis were observed in nanoparticle-treated groups compared with irradiation alone. Radiosensitization demonstrated strong size dependence, with 50 nm AuNPs producing the greatest enhancement, a finding that may reflect size-dependent differences in cellular internalization, intracellular distribution, and nanoscale energy deposition previously established in AuNP studies. Importantly, biological effects intensified at later post-irradiation intervals, demonstrating a sustained temporal evolution of the radiobiological response beyond the initial irradiation event, potentially involving oxidative and other delayed cellular stress mechanisms described in AuNP radiosensitization. Conclusions: These findings demonstrate the capacity of AuNPs to enhance the radiobiological response of cervical cancer cells to ¹⁹²Ir brachytherapy and identify nanoparticle size and post-irradiation time as important determinants of this effect. They therefore support AuNP-assisted brachytherapy as a promising strategy for further development toward biologically optimized radiotherapy capable of improving tumor response without escalation of the prescribed radiation dose. Full article

Colibacillosis caused by avian pathogenic Escherichia coli (APEC) remains an important bacterial disease in poultry production and is increasingly difficult to control because of antimicrobial resistance. In this study, a lytic phage, ND-4, was isolated from poultry-farm sewage using the O2:K1 APEC strain IMT5155 as the host, and its biological characteristics, genome features and preliminary application potential were evaluated. ND-4 formed clear plaques on IMT5155 and showed a tailed morphology, with an elliptical head of 110 ± 5 nm by 82 ± 5 nm and a tail of 97 ± 5 nm by 18 ± 2 nm, giving a total virion length of approximately 204 ± 10 nm. The phage had an optimal multiplicity of infection of 0.01, a latent period of 20 min, a 50 min burst period and a burst size of 231 PFU/cell. ND-4 remained active across pH 4–9 and at temperatures up to 60 °C, and it retained titers above 10⁸ PFU/mL after exposure to chloroform concentrations up to 15%. Whole-genome sequencing revealed a 154,669 bp double-stranded DNA genome with 184 predicted open reading frames and a G + C content of 48.98%. No virulence or antimicrobial resistance genes were detected. ND-4 reduced biofilm biomass in vitro and decreased tissue bacterial loads and alleviated hepatic inflammation and vacuolar degeneration in IMT5155-challenged chicks. These results indicate that ND-4 is a promising candidate for further development as a phage-based control agent against APEC infection, although larger in vivo studies are needed to define its efficacy, dosing window and biosafety profile. Full article

This study examined the distribution of 24 metal(loid)s in muscle, liver, gills, and gonads of dominant fish species from Vrana Lake, Croatia. Element concentrations were determined by inductively coupled plasma mass spectrometry (ICP-MS). The effects of tissue type, species, fish size, and season were evaluated using classical statistics, principal component analysis (PCA), and the Neural Gas (NG) algorithm. Tissue type was the primary determinant of elemental composition. Concentrations of most elements were highest in liver and gills, intermediate in gonads, and lowest and most uniform in muscle. Species-related differences were generally limited, while size-related relationships were tissue- and species-dependent, with generally weak or negative trends in muscle and more variable responses in metabolically active organs. PCA revealed clear tissue-based structuring but comparatively limited separation among species. NG complemented these findings by providing additional resolution of within-tissue heterogeneity and low-frequency multielement profiles. Overall, our findings provide a baseline reference dataset for the biota of Vrana Lake, indicate tissue physiology as the main factor influencing elemental variability, and indicate that NG may serve as a useful complementary approach for exploring complex multielement biomonitoring data. Full article

Background/Objectives: Irritable bowel syndrome (IBS) may have health implications beyond the gastrointestinal tract, but its association with incident hypertension remains unclear. Methods: We analyzed 355,404 UK Biobank participants without recorded hypertension at baseline using multivariable Cox regression, propensity score matching, and sensitivity analyses addressing early events, baseline medication use and blood pressure, and competing mortality. Bidirectional Mendelian randomization (MR), Bayesian colocalization, and intestinal transcriptomic analyses examined genetic and tissue-level evidence. Results: During a median follow-up of 14.09 years, IBS was associated with incident hypertension (HR, 1.26; 95% CI, 1.22–1.30). The association persisted after matching (HR, 1.22; 95% CI, 1.16–1.28) and across sensitivity analyses. Forward MR provided suggestive support: the primary inverse-variance weighted estimate was positive but imprecise (OR, 1.18; 95% CI, 0.78–1.77), while weighted median and outlier-corrected analyses showed positive associations. Reverse MR showed no clear association. SuSiE-based colocalization supported shared signals for IBS with diastolic and systolic blood pressure at the NCAM1 locus (PP.H4, 0.903 and 0.890, respectively). Intestinal NCAM1 expression was lower in IBS, and correlated transcriptional programs involved epithelial remodeling, adhesion, and mucosal immune processes. Conclusions: IBS was associated with increased long-term hypertension risk, with suggestive genetic support and shared susceptibility signals at NCAM1. These findings support a potential biological link and prioritize NCAM1 for mechanistic investigation. Full article

Oxidative stress and persistent inflammation can compromise tissue repair and the performance of locally delivered biomaterials. Here, we developed an aqueous alginate–lysozyme–tannic acid biohybrid hydrogel designed to combine injectability, antioxidant functionality, and extrusion-based printability. A composition screen varying alginate and lysozyme at a fixed tannic acid concentration identified a clear balance between flowability and structural integrity. An intermediate formulation provided shear-thinning and elastic-dominant rheological behavior, controlled hydration, cytocompatibility, antioxidant activity, and practical syringe/nozzle extrusion. The selected formulation was transferable to an approximately 80 mL batch and could be deposited into a multilayer structure. The findings are consistent with the formation of a cooperative polysaccharide–protein–polyphenol network and demonstrate the feasibility of integrating redox functionality with material processability. Future studies should focus on quantitative print fidelity validation, molecular interaction analysis, lysozyme activity retention, longer term stability, and application-relevant in vivo evaluation. Such development may support the future translation of injectable and printable antioxidant biomaterials for chronic wound management and tissue regeneration applications. Full article

Introduction: Salvage surgery is known for an increased surgical complication rate. However, currently available patient, tumor and therapy factors are not reliable enough to predict surgical site complications (SSCs). This exploratory study tests skin acquired by neck dissection for several histochemical and immunohistochemical stains to explore tissue changes related to wound healing. Patients and methods: From an existing database of 232 isolated neck dissections (NDs), 17 patients who underwent skin resection during ND were included—5 who underwent primary procedures and 12 who underwent salvage procedures. Skin specimens were tested for ten histochemical and immunohistochemical stains, with emphasis on the stages of wound healing: inflammation, proliferation and remodeling. Results: Three stains (CD-68, α-SMA, and Vimentin) showed significantly different expression between the primary surgical and salvage groups (respectively. p = 0.013, p = 0.044 and p = 0.015), without a clear pattern of decreased or increased expression. None of the ten stains showed a significant difference related to SSCs. Conclusions: The three significantly different staining patterns found in this exploratory study can all be linked to macrophage and (myo-)fibroblast transitions, possibly representing an imbalance of macrophage/stroma interplay. Future studies focusing on the role of macrophages in wound healing after salvage surgery are necessary. Full article

Despite major advances in exercise physiology, biomechanics, and mechanobiology, exercise science still lacks a clear conceptual definition of the mechanical stimulus experienced by skeletal muscle during resistance training. Current approaches rely on diverse external, internal, and biomechanical variables (e.g., volume-load, force, power, velocity, time under tension, or muscle architecture), yet none individually captures the muscle-specific mechanical exposure relevant to muscular adaptation. This conceptual inconsistency limits comparisons across studies, complicates training prescription, and hinders the development of individualized monitoring strategies. This integrative review critically synthesizes current evidence from mechanobiology, skeletal muscle physiology, biomechanics, and resistance training to examine how mechanical stimuli are currently conceptualized, quantified, and interpreted. Based on this synthesis, we propose a working definition of Mechanical Dose as the cumulative, muscle-specific mechanical exposure experienced over a defined time window, characterized by loading magnitude, rate, duration, frequency, and spatial distribution, and conditioned by contraction mode and muscle–tendon geometry. Rather than representing a directly measurable variable, mechanical dose is presented as a latent conceptual construct that can only be estimated through combinations of biomechanical, physiological, and morphological indicators. Building upon this definition, we introduce an integrative conceptual framework linking external load, movement biomechanics, mechanical dose, mechanotransduction, and tissue adaptation. We further discuss how this framework may guide future research on the interpretation of field-based monitoring, resistance training prescription, recovery management, and future explainable artificial intelligence approaches in sport science. By reframing mechanical dose as the central construct connecting biomechanics and biological adaptation, this review provides a unified conceptual basis for future research and contributes toward a more biologically informed paradigm of exercise prescription and monitoring. Full article

Background: Eukaryotic translation elongation factor 1 alpha 1 (EEF1A1) primarily participates in protein synthesis by binding aminoacyl-tRNA complexes to facilitate peptide chain elongation on ribosomes. Its expression and functional roles exhibit significant heterogeneity across various malignancies, exerting dual regulatory effects as both an oncogene and a tumor suppressor. This study aims to investigate the potential prognostic value and tumor-suppressive role of EEF1A1 in kidney renal clear cell carcinoma (KIRC). Methods: We analyzed the differential expression of EEF1A1 in KIRC and its correlation with patient prognosis based on the TCGA, GEO, and HPA databases. The STRING and GEPIA databases were utilized to perform functional enrichment analysis of its interacting proteins and co-expressed genes. The xCell algorithm was employed to assess the correlation between EEF1A1 and immune cell infiltration, immune checkpoints, and immunomodulatory molecules. Furthermore, drug sensitivity analysis was conducted to evaluate its clinical application potential. Finally, the expression of EEF1A1 in 786-0 and A498 cell lines was validated via qRT-PCR and Western blotting. Furthermore, CCK-8, wound healing, and Transwell migration/invasion assays were performed to evaluate cell proliferation, migration, and invasion, respectively. Results: EEF1A1 may function as a negative regulator of malignant behaviors in KIRC tissues and cell lines, and its expression level was closely associated with clinicopathological features and prognosis of patients. GO, KEGG, and GSEA enrichment analyses revealed that low EEF1A1 expression is closely linked to immunosuppressive pathways. Further immunological analysis confirmed significant correlations between EEF1A1 and various immune cell infiltrates, immune checkpoints, tumor-infiltrating lymphocytes, and immunomodulatory molecules. Moreover, cells with high EEF1A1 expression exhibited increased sensitivity to anti-tumor drugs, with expression levels negatively correlated with inhibitory activity (IC50). Finally, overexpression of EEF1A1 significantly inhibited the proliferation, migration, and invasion of clear cell renal cell carcinoma cells. Conclusions: EEF1A1 serves as a potential prognostic biomarker in KIRC and is associated with clinical progression, immune-related characteristics, metabolic pathways, and drug sensitivity. Functional validation further supports its role in regulating malignant phenotypes of KIRC cells. Full article

While nanoplastics (NPs, <1 µm) concentration is anticipated to increase in the marine environment, the analytical tools for NP quantification and data on their impacts are still scarce. This work aimed to expand knowledge regarding bioaccumulation and effects of NPs on the sentinel organism Mytilus galloprovincialis. For this, mussels were dietarily exposed for 7 days to model palladium-doped-polystyrene NPs (Pd-PS NPs) of 142.6 ± 1.0 nm at 1 × 10⁹ Pd-PS NPs/mL. ICP-MS analysis on water samples showed that after one day of exposure no Pd was detected suggesting that mussels cleared the NPs. After 7 days of exposure, 14% of the Pd introduced in the tanks was found in feces. Less than 0.02% passed into the hemolymph of mussels and consequently, no responses were observed on hemocytes. Approximately 1% of the Pd was found in soft tissues. This could be linked to the significantly higher prevalence of digestive tubule atrophy observed in exposed mussels in comparison to controls. No effects were observed at the whole organism level. In conclusion, mussels were able to uptake and to eliminate Pd-PS NPs through feces. Whether longer exposures could cause a significant accumulation of NPs and produce associated biological effects remains to be studied. Full article

Porcine reproductive and respiratory syndrome virus is a major pathogen that causes massive economic losses in the global swine industry. Lysine propionylation and malonylation are metabolism-sensitive post-translational modifications, yet their coordinated regulatory roles during PRRSV pulmonary infection remain unknown. This study combined quantitative proteomics, propionylome and malonylome to characterize host molecular alterations between healthy and PRRSV-infected porcine lung tissues (three piglets per group). Quantitative proteomics identified 1467 significantly downregulated proteins and only 129 upregulated proteins, indicating a profound host protein shutoff during PRRSV pulmonary infection. The two acyl modifications displayed opposite regulatory patterns independent of global protein expression changes: 51 propionylation sites (24 proteins) were upregulated with only 1 downregulated, while 37 malonylation sites (30 proteins) were downregulated and only 5 upregulated. Functional enrichment and PPI network analysis revealed clear functional divergence: hyper-propionylated hub proteins were exclusively enriched in mitochondrial energy metabolism pathways, whereas hypo-malonylated core proteins were mainly involved in lipid metabolism and cell fate regulation. Integrated multi-omics analysis confirmed that protein expression and lysine acylation constitute two coordinated but independent regulatory layers, with histone H4 identified as a candidate target of competitive propionylation/malonylation. This work reports the comprehensive landscape of lysine propionylation and malonylation upon PRRSV infection, reveals a dual-PTM remodeling strategy for viral hijacking of host homeostasis, and provides candidate targets for future functional investigation and antiviral development. Full article

Human skin remains difficult to model in vitro because it brings together stratified epidermal, dermal, hypodermal, vascular, immune, appendageal, neural, and microbial elements within a single tissue. Traditional two-dimensional cultures and animal models still offer useful insight, but both have clear translational limits. Three-dimensional (3D) human skin models have therefore become increasingly valuable for mechanistic, pharmacologic, and regenerative research. This narrative review followed a fit-for-purpose literature selection framework. Priority was given to primary studies and reviews published between 2019 and 2025 that reported major advances in model architecture, biomaterials, vascularization, immune integration, appendage formation, sensorization, or translational application. Greater weight was given to studies that linked added complexity to measurable functional outputs. Current platforms include organotypic human skin equivalents, bioprinted constructs, microfluidic skin-on-a-chip systems, and pluripotent stem cell-derived organoids. Important advances include self-assembled or decellularized matrices that more closely reflect native extracellular matrix composition, perfusable microvasculature, hypodermal incorporation, immune cell integration, and real time sensing. These systems now support work in barrier testing, safety testing, dermal drug development, inflammatory dermatoses, melanoma, wound healing, aging, and regenerative transplantation. No single platform fully reproduces native human skin. The more relevant question is not how much complexity can be added, but which added features meaningfully improve performance for a defined endpoint. A fit-for-purpose framework may offer a better basis for model selection, benchmarking, standardization, and translational adoption. Future progress will depend on application specific validation, clearer performance benchmarks, scalable manufacturing, and closer alignment with regulatory and clinical needs. From that perspective, 3D skin models are best understood as complementary platforms for translational dermatology research. Full article

Portable handheld bioprinters represent a transformative advancement in personalized skin regeneration, bypassing the logistical constraints of stationary lab-based systems by enabling real-time, in situ fabrication of bioengineered constructs directly within the wound bed. This review aims to evaluate the current state of their development and clinical translation. One of the foci is placed on the stringent physicochemical requirements for bioinks, where we examined the critical balance between bioadhesion—facilitated by functional groups—and mechanical cohesion necessary for maintaining structural integrity during deposition, while RGD motifs are considered primarily as promoters of integrin-mediated cell adhesion. Preclinical studies have demonstrated promising effects of bioprinted constructs on wound healing and tissue organization; however, human evidence for handheld and direct in situ skin bioprinting remains limited, and clinical efficacy has yet to be established in controlled studies. Nevertheless, widespread adoption is hindered by inferior printing fidelity relative to stationary counterparts, a lack of standardized GMP-compliant bioink production, and regulatory ambiguity that impedes clear classification as either medical devices or biologics. Practical barriers, including intraoperative sterility assurance and operator training, also remain unresolved. Looking ahead, we discuss how the convergence of, in particular, artificial intelligence for real-time wound morphometry, closed-loop process control, and smart, self-healing biomaterials promises to surmount these obstacles. We conclude that these synergistic innovations may propel handheld bioprinters from experimental prototypes toward clinical tools with the potential to reshape reconstructive surgery and emergency wound care, although their clinical value will require validation in appropriately designed human studies. Full article

Human induced pluripotent stem cell (iPSC)-derived neural organoids have emerged as valuable models for investigating human neurodevelopment and neurological disorders. However, their complex three-dimensional architecture poses significant challenges for conventional histological approaches, which rely on physical sectioning and inevitably disrupt spatial relationships within the tissue. Volumetric imaging of intact organoids typically requires light-sheet fluorescence microscopy, a technology not widely accessible to standard cell biology laboratories. Here, we show that solvent-based tissue clearing, using the iDISCO+ and Visikol^® HISTO protocols, combined with conventional laser-scanning and spinning-disk confocal microscopy, platforms already available in most imaging facilities, is sufficient to resolve neuroepithelial rosette-like structures, neuronal networks, and astroglial components within intact human cortical and retinal organoids, while preserving immunofluorescent labeling and tissue architecture. The workflow was also compatible with commonly used immunofluorescence markers. Although light-sheet fluorescence microscopy remains advantageous for large-scale whole-sample imaging, our results show that cleared human organoids within the size range analyzed here can be effectively visualized using accessible confocal systems. This study provides a practical strategy for three-dimensional imaging of intact human neural organoids, facilitating spatial analysis of developmental organization and disease-relevant phenotypes in laboratories without dedicated light-sheet microscopy infrastructure. Full article

The management of chronic wounds represents one of the major challenges in regenerative medicine, as the healing process can be compromised by infections, oxidative stress, and persistent inflammation. In this context, wound pH serves as an important biomarker of tissue status, highlighting the need for smart dressings capable of promoting regeneration while simultaneously monitoring the wound microenvironment. In this study, biomimetic silk fibroin films functionalized with curcuminoids extracted from Curcuma longa were developed and characterized through spectroscopic, swelling/degradation, antioxidant, colorimetric, and biological assays, with the aim of obtaining a multifunctional dressing with regenerative properties and pH responsiveness. The results showed that curcuminoids were physically incorporated into the protein matrix without altering its chemical structure. The films exhibited a high absorption ability and antioxidant activity in the initial stages, and a clear and reversible color change in response to pH. Biological assays on 3T3 fibroblasts further confirmed the high cytocompatibility of the materials and their ability to support cell migration and wound closure in vitro. The developed films represent a promising biomimetic platform for advanced wound dressings, capable of combining support for tissue regeneration, antioxidant protection, and visual monitoring of wound status through the detection of pH changes. Full article

Background: Endometriosis-associated ovarian cancers (EAOCs), including ovarian clear cell (OCCC) and endometrioid ovarian carcinoma (EnOC) subtypes, frequently exhibit transcriptomic dysregulation of the PI3K/AKT/mTOR signalling axis. While genomic aberrations are well-documented, the coordinated microRNA (miRNA)-mediated networks governing post-transcriptional remodelling of this pathway across these subtypes remain poorly defined. Methods: We conducted an integrative in silico meta-analysis of independent mRNA and small RNA sequencing datasets. The mRNA analysis included 120 EAOC samples, of which 68 were OCCC and 52 were EnOC, compared with 149 normal ovarian tissues. The miRNA analysis included 170 samples comprising 55 OCCC, 82 EnOC and 33 normal ovarian tissues. Differential expression analysis, dimensionality reduction (UMAP), functional enrichment, and topologically unweighted miRNA–mRNA interaction networks were evaluated. Results: Both subtypes showed significant transcriptomic dysregulation of the core pathway machinery, including PIK3CB and mTOR, while preserving mTORC2 components. Post-transcriptional concurrent downregulation of IRS1, GRB10, DDIT4, and PIK3CD, which were identified as candidate targets of the hub miRNAs hsa-miR-30a-5p, hsa-miR-30d-5p, and hsa-miR-7-5p, suggests further refined control of the pathway. The identification of highly connected hub genes linking mTOR, MAPK, and Wnt signalling pathways within the mTOR-regulatory network suggests that pathway modulation occurs through extensive crosstalk across multiple oncogenic signalling pathways in EAOCs. Conclusions: Transcriptomic dysregulation of the mTOR pathway in EAOCs reflects not only genomic alterations but also potential post-transcriptional regulation. Despite subtype-specific transcriptomic differences, both exhibited transcriptional upregulation of components of the canonical PI3K/AKT/mTOR signalling axis. Pathway modulation through the miRNA regulatory network exhibited potential crosstalk across oncogenic pathways and hub genes. Full article