Search Results (9,562)

Background/Objectives: Osteoporosis poses significant obstacles as it causes an imbalance between osteoblasts and adipocytes, which results in the disruption of bone homeostasis. Although various magnesium-based scaffolds have been deployed for the treatment of osteoporotic bone defects, whether this can be achieved by alleviating bone–fat imbalance still requires further elucidation. Methods: We designed magnesium phosphate-based platforms (GMPCs), based on magnesium photopolymerized methacrylated gelatin (GelMA) and phosphate (K-struvite, MPC), and used them to deliver magnesium ions (Mg²⁺) for alleviating bone–fat imbalance locally. Results: The in vivo results demonstrated that the GMPCs not only improved osteogenic behavior at the implanted site, but also reduced the proportion of adipose tissues in a femoral defect model in 18-month-old SD rats. Moreover, by promoting the differentiation of bone marrow mesenchymal stem cells (BMSCs) into osteoblasts in a concentration-dependent manner, GMPCs significantly reduced adipogenic differentiation in vitro. Also, 5GMPC demonstrated the best comprehensive biologic properties compared to other platforms. Conclusions: GMPCs have great potential in the treatment of age-related osteoporosis via the effective delivery of Mg²⁺. Full article

Cardiovascular disease (CVD) remains the leading cause of mortality worldwide, driving the continuous evolution of implantable cardiovascular therapies. Although early cardiovascular implants revolutionized the treatment of CVD, they are limited by restenosis, mechanical failure, poor biocompatibility, and inadequate tissue integration. These clinical limitations have driven the development of next-generation implants, with improved hemodynamic performance, regenerative potential, and long-term functionality. Advances in biomaterial science, tissue engineering, biosensors, wireless telemetry, flexible bioelectronics, and translational cardiovascular medicine have transformed cardiovascular implants from passive structural devices into biologically integrated and increasingly intelligent systems capable of interacting dynamically with the host cardiovascular environment. In this review, we summarize the historical evolution, current clinical applications, and emerging technologies of major cardiovascular implants. We further discuss key biological and engineering challenges limiting long-term clinical success and highlight future directions in regenerative biomaterials, smart bioelectronics, and personalized cardiovascular implants for next-generation cardiovascular therapy. Full article

Extracellular vesicles (EVs) have emerged as key mediators of intercellular communication in the brain, with glial cell-derived EVs increasingly recognized for their roles in maintaining brain homeostasis and contributing to the progression of neurodegenerative diseases. By transferring a diverse cargo of bioactive molecules, including proteins, RNAs, and organelles, EVs influence recipient cell behavior and overall brain function. In neurodegenerative conditions, glial EVs can either propagate pathogenic signals or deliver neuroprotective and regenerative cues, depending on their cellular origin and molecular composition. This context-dependent heterogeneity highlights the need for physiologically relevant human models to investigate EVs biology. Human induced pluripotent stem cell (iPSC)-derived glial models provide a disease-relevant platform, as they recapitulate key pathological features of Alzheimer’s disease (AD), Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS). When further integrated with brain organoid platforms, these iPSC-based systems enable the generation of three-dimensional environments that closely resemble in vivo EVs dynamics. Importantly, glial EVs can modulate cellular pathways involved in neuronal survival and function. Indeed, their potential to interact with and, under specific experimental conditions, traverse the blood–brain barrier (BBB) has contributed to growing interest in their application for biomarker discovery and therapeutic development. Engineered and patient-specific EVs derived from iPSCs are emerging as promising tools for targeted, cell type-specific, therapeutic approaches, although their clinical applicability still requires further validation. This review discusses the emerging evidence supporting the dual role of iPSC-derived glial EVs in health and disease, underscores the translational potential of iPSC-based platforms for mechanistic studies, and outlines their promise as precision medicine tools for diagnostics and therapy. Full article

The synthesis of reactive sucrose derivatives is of significant interest for the development of novel biocompatible polymers. In this study, an octa-substituted sucrose derivative containing isocyanate groups was synthesized via a urethane-forming reaction carried out in an aprotic solvent at the phase interface. This approach exhibits high selectivity and provides a target product yield of up to 60%. Subsequently, using the same reaction mechanism, the isocyanate derivative was converted into an octa-functional methacrylate derivative capable of forming three-dimensional cross-linked networks. The structures of both the intermediate and final products were confirmed by IR, ¹H NMR, and mass spectrometry. The sucrose-based prepolymer was further evaluated in the formation of cross-linked structures for potential application as bone-substituting implants. Using various photocuring techniques, including two-photon 3D printing, both plates and microstructured scaffolds were fabricated. These structures exhibited high thermal stability, elastic properties comparable to those of bone tissue, and no toxic effects on cells. Full article

Epigenetics regulates gene activity without altering the underlying DNA sequences. Numerous studies have highlighted the importance of epigenetics in diverse physiological processes, including cell growth, differentiation, and tissue development. Increasingly, epigenetic modifications are recognized for their involvement in various diseases, notably corneal disorders. Corneal fibrosis, a common consequence of ocular injury or infection, significantly contributes to visual impairment and blindness worldwide. Recent evidence indicates that epigenetic changes regulate key processes in corneal pathogenesis, such as inflammation, wound healing, extracellular matrix remodeling, fibrosis, and neovascularization. These findings underscore the potential of developing novel therapeutic strategies that specifically target epigenetic mechanisms to treat or mitigate corneal pathology. Nevertheless, bringing epigenetic therapies into clinical practice remains challenging given the complexity of epigenetic regulation. Future research leveraging multi-omics technologies and specific gene manipulation will be essential to elucidate the mechanisms underlying epigenetic regulation in corneal diseases and to identify specific therapeutic targets. Such advancements will drive the development of effective, clinically relevant treatments for corneal fibrosis and related disorders. Full article

Neoadjuvant therapy (NAT) is a standard component of breast cancer treatment, yet response rates vary substantially across patients. Accurate prediction of pathological complete response remains an unmet clinical need to improve patient selection for NAT. This review summarizes current approaches of using computer vision to predict breast cancer response to NAT from histopathological slides. We examined studies employing computer vision and machine learning models on hematoxylin and eosin and immunohistochemically stained whole-slide images, focusing on morphological features of tumor cells, stroma and tumor-infiltrating lymphocytes associated with pathological complete response. Key morphological predictors of therapy resistance included low tumor cell density with cord-like patterns, necrosis, predominance of collagenous and fibroblast-rich stroma and tumor vascularization, while therapy sensitivity was associated with high nuclear staining intensity, high tumor cell density and lymphocyte infiltration. We highlighted the advantages of incorporating multimodal data to enhance predictive performance. Our analysis demonstrates that computer vision models can detect subtle morphological patterns that may be difficult for pathologists to evaluate, providing valuable insights for personalized therapy planning in breast cancer. Further development of cross-modal, interpretable artificial intelligence solutions may improve prediction accuracy and deepen our understanding of tumor biology relevant to NAT response. Full article

Background: Cenobamate is a novel antiseizure medication with potential interactions involving cytochrome P450 enzymes, including CYP2C19. Genetic variability in CYP2C19 may influence drug metabolism and tolerability, although its clinical relevance in cenobamate-treated patients remains unclear. Methods: We conducted a single-center retrospective study including 48 adults with drug-resistant epilepsy treated with cenobamate. Patients were stratified by concomitant use of CYP2C19-substrate ASMs (patients with CYP2C19 substrates vs. patients without CYP2C19 substrates). CYP2C19 genotype was classified into metabolizer phenotypes. Adverse events (AEs) were categorized as potentially CYP-mediated or likely unrelated to CYP-mediated pharmacokinetic mechanisms based on clinical assessment, temporal association, and known pharmacological interaction profiles. Associations were explored using descriptive statistics and regression models. Results: Overall, 58.3% of patients received CYP2C19-substrate ASMs. AEs were more frequent among patients with CYP2C19 substrates (71.4% vs. 20.0%; p = 0.001), with potentially CYP-mediated AEs observed only in this group (32.1% vs. 0%; p < 0.001). Intermediate metabolizers showed a higher proportion of potentially CYP-mediated AEs (87.5%; p < 0.001). This pattern was not observed in patients without CYP2C19 substrates. Regression analyses suggested increased risk in intermediate metabolizers, although estimates were imprecise and should be considered exploratory. Conclusions: An exploratory association between CYP2C19 variability and AE occurrence was observed in patients treated with cenobamate combined mainly with clobazam and other CYP2C19-substrate ASMs. Intermediate metabolizers may represent a higher-risk subgroup, but these preliminary findings require prospective confirmation with pharmacokinetic monitoring. Full article

Dog aggression toward humans represents a relevant public health issue. In Italy, small animal veterinarians are expected to contribute to the early identification of at-risk situations and to aggression prevention. This study aimed to assess, through a nationwide survey, veterinarians’ perception of this role, regulatory awareness, and clinical practices related to dog aggression prevention in Italy. A cross-sectional study was conducted between November 2025 and February 2026 using an anonymous online questionnaire disseminated through provincial veterinary boards to private veterinarians working in small animal practice. A total of 1088 valid responses were analyzed using descriptive, inferential, and multivariable analyses. Almost all respondents reported frequent encounters with aggressive behavior, with more than 60% managing at least five aggressive dogs per year. Although 80% recognized an active preventive role for veterinarians, only 55% were aware of the current Ministerial Ordinance and 19% had ever submitted a report to public veterinary services. Specific training in behavioral medicine was independently associated with greater regulatory awareness and reporting behavior. Strong support also emerged for mandatory owner training and early behavioral assessment. A substantial gap persists between the preventive role assigned to veterinarians and the practical implementation of preventive tools. These findings support the need for strengthened behavioral medicine training and improved integration between private practitioners and public veterinary services. Full article

Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disorder characterized by persistent airflow limitation and chronic airway inflammation. Current therapeutic strategies primarily offer symptomatic relief and are often limited by systemic side effects, inadequate lung deposition, and poor patient compliance. Naringin (NAR), a natural flavonoid with strong antioxidant, anti-inflammatory, and anti-fibrotic activities, has demonstrated potential in mitigating COPD-associated pathophysiology. However, its therapeutic application is restricted by poor water solubility, low bioavailability, and rapid metabolism. Nanotechnology-based drug delivery systems, particularly poly(lactic-co-glycolic acid) (PLGA) nanoparticles, provide an effective approach for lung-targeted therapy. Their nanoscale size promotes deep lung deposition, enhanced cellular uptake, reduced lung clearance, improved therapeutic efficacy, and reduced systemic side effects. The present study aimed to develop NAR-loaded PLGA nanoparticles (NAR PLGA NP) for enhanced cell-targeting in inflammatory lung conditions. NAR PLGA NP were prepared using the emulsion solvent evaporation method, with PLGA in the organic phase and soya lecithin (SL) with poly(vinyl alcohol) (PVA) as surfactants in the aqueous phase. A face-centered central composite design was employed to optimize the formulation. The optimized nanoparticles were characterized for size distribution by dynamic light scattering, entrapment efficiency, Transmission Electron Microscopy (TEM), Fourier Transform Infrared (FTIR), Differential Scanning Calorimetry (DSC), X-Ray Diffraction (XRD), and in vitro drug release. The safety of PLGA and lecithin-coated PLGA nanoparticles (LC PLGA NP) was assessed using an MTT assay on lung epithelial cells, followed by cellular uptake studies, angiogenesis by chick Yolk Sac Membrane (YSM) assay, and in vitro evaluation of reactive oxidative stress (ROS) and anti-inflammatory activity. The optimized PLGA formulation showed a hydrodynamic diameter of 201 ± 1 nm with PDI 0.20 ± 0.03 and EE of 76.11 ± 2.1%, and 81.7 ± 4.9% drug release at 72 h, whereas LC PLGA NP showed a hydrodynamic diameter of 308 ± 3 nm, PDI of 0.21 ± 0.05, entrapment efficiency of 82.45 ± 4.8%, and 71.4 ± 3.2% drug release at 72 h. Both PLGA NP and LC PLGA NP demonstrated good cytocompatibility with lung epithelial cells, efficient cellular uptake, and a significant reduction in intracellular reactive oxygen species (ROS) levels (**** p value < 0.0001). Moreover, the formulations markedly suppressed pro-inflammatory cytokines, including TNF-α, IL-6, and IL-1β, indicating anti-inflammatory activity. The angiogenesis assay further suggested their ability for lung tissue repair and remodeling. These findings support the potential of LC PLGA NP as a promising cell-specific targeting system for naringin in inflammatory lung conditions. Full article

Background/Objectives. The modern Western diet (MWD) provides high linoleic acid (LA) exposure, typically contributing 6–9% of the total caloric intake. These high LA levels have fueled a longstanding debate about whether this dietary pattern confers benefit or risk. Importantly, LA intake is disproportionately elevated among lower socioeconomic populations due to greater reliance on industrial seed oils and ultra-processed foods. Despite decades of research, controlled dietary intervention studies directly evaluating the biological consequences of varying LA exposure remain limited. Methods. The current randomized, double-blind intervention (ClinicalTrials.gov; NCT02962128; 11 November 2016) compared the effects of a 12-week Low-LA diet (2.5% energy) versus a High-LA diet (10.0% energy) in healthy adults. Outcomes included plasma concentrations of highly unsaturated fatty acids (HUFAs) and ex vivo zymosan-stimulated whole-blood oxylipin generation. Results. Fifty-two participants completed the intervention. High LA exposure resulted in marked reductions in plasma n-3 eicosapentaenoic acid (EPA) and eicosatetraenoic acid (ETA) concentrations compared with the Low-LA arm. Docosapentaenoic acid (DPA) was also significantly lower in weeks 4 and 8. In contrast, levels of the n-6 HUFA arachidonic acid (ARA) did not differ with dietary LA exposure. Conclusions. HUFA and oxylipin analyses revealed that higher dietary LA markedly increased the ratios of ARA to EPA and ARA- to EPA-derived oxylipin species, shifting the lipid mediator balance toward a more n-6-dominant inflammatory profile. Full article

Multidrug-resistant organisms, particularly carbapenem-resistant Enterobacterales (CRE), represent a major global health threat. In settings with endemic circulation of carbapenem-resistant organisms, early identification of colonised patients before hospital admission may play a critical role in limiting in-hospital spread and guiding infection prevention strategies. We conducted a retrospective monocentric observational study including all patients evaluated for hospital admission in 2025. Patients presenting predefined epidemiological or clinical risk factors underwent risk-based pre-admission screening for CRE. Patient-level deduplication was applied to microbiologically positive records. Among 2694 patients evaluated for hospital admission, 1084 met predefined screening criteria and underwent rectal swab testing. Overall, 191 unique patients were confirmed as carriers of carbapenemase-producing Enterobacterales, corresponding to 17.6% of screened patients and 7.1% of the overall cohort evaluated for admission. KPC was the most prevalent carbapenemase gene (102/191, 53.4%), followed by NDM (57/191, 29.8%) and KPC/NDM co-production (14/191, 7.3%). Less frequent gene profiles included VIM, OXA-48, and combined carbapenemase patterns. In high-endemic healthcare settings, risk-based pre-admission screening may represent a pragmatic component of infection prevention pathways by supporting early identification of patients with probable CRE/CPE carriage. When analysed at the patient level, such programmes can provide useful operational and epidemiological information for admission management and infection control planning. Full article

Improvement of bowel function is accompanied by increased luminal flow and altered epithelial mechanical forces, yet the underlying epithelial mechanisms remain unclear. We investigated whether enhanced luminal stimulation is associated with epithelial mechanotransduction and junctional remodeling during changes in colonic motility. Sennoside was orally administered at 4.8 mg/kg body weight to 5-week-old male BALB/cAJcl mice for 21 days to model increased luminal stimulation. Stool characteristics, fecal water content, Bristol Stool Form Scale scores, and segmental colonic motility were assessed. Expression of Muc2, inflammatory cytokines, Trpv4, and E-cadherin was quantified across colonic regions. In CT26 monolayers, mechanical stress was applied to evaluate transient receptor potential channel induction, E-cadherin redistribution, and transepithelial electrical resistance, and the effect of Trpv4 knockdown. Sennoside softened stools, increased fecal water content (+18%) and Bristol scores (+57%), and enhanced distal colonic motility (+117%) without altering inflammatory cytokines. Trpv4 was selectively upregulated in the distal colon (3.3-fold). E-cadherin expression increased (2.5-fold) with junctional redistribution, whereas Muc2 decreased (−44%). In vitro, mechanical stress upregulated Trpv4 (2.5-fold), increased barrier resistance (+48%), and promoted E-cadherin assembly; these effects were augmented by sennoside and attenuated by Trpv4 silencing. These findings suggest that epithelial responses involving TRPV4-associated mechanotransduction and junctional remodeling are associated with altered barrier-related properties and distal colonic functional changes, providing insight into an epithelial component of stimulant laxative action. Full article

Background: Primary malignant bone tumors of the pelvis account for 10–15% of all primary bone sarcomas, most commonly chondrosarcoma, osteosarcoma, and Ewing’s sarcoma. Although advances have shifted treatment toward internal hemipelvectomy, pelvic resections remain challenging due to the complex anatomy. The need for pelvic reconstruction is controversial, balancing potential stability against higher complication rates. This review evaluates the role of pelvic ring reconstruction, focusing on techniques, outcomes, and complications. Methods: A systematic literature review was performed in June 2025 using PubMed, MEDLINE and Cochrane Library as the primary databases, with the following search string: (hemipelvectomy) AND (orthopedic), acknowledging that this search strategy may be limited in scope. Studies published within the last five years were considered. After performing a full-text assessment of 80 studies, 14 studies were included in this review. Data regarding patients, methods, and outcomes were extracted and summarized. Results: Among the 14 included studies, seven investigated patient-specific three-dimensional (3D) printed pelvic reconstructions, four reported biological reconstruction techniques, two studies focused on non-reconstructive management and one study evaluated alternative stabilization using segmental spinal instrumentation. 3D printed and other reconstructive techniques were associated with improvements in the Musculoskeletal Tumor Society score, reduced pain, and demonstrated osseointegration with few mechanical failures. Although individual case series demonstrated good ambulation and stable fixation, complication rates, particularly wound and infection-related events, remained frequent. Type III reconstructions and personalized implants showed the highest functional gains but occasionally revealed asymptomatic fretting wear. In contrast, the only Level I evidence indicated significantly higher complication and infection rates in reconstructed patients and better functional outcomes in those managed without reconstruction when spinopelvic stability was preserved. Non-reconstructive strategies, including spinal instrumentation, supported early ambulation with low mechanical failure, while pediatric patients treated without reconstruction experienced a high complication rate but acceptable long-term oncologic outcomes. Conclusions: Current evidence suggests that routine pelvic ring reconstruction after internal hemipelvectomy may not be justified based on the currently available evidence. Patient-specific 3D-printed implants appear to provide consistent improvements in function, pain reduction, and mechanical stability, but are associated with a relevant risk of wound-related and infectious complications. In patients with preserved spinopelvic stability, non-reconstructive strategies may achieve comparable functional outcomes with lower morbidity. Therefore, pelvic reconstruction should be performed selectively, and further prospective multicenter studies are needed to better define appropriate patient selection and optimize reconstructive strategies. Full article

Mesenchymal stromal cell (MSC) adhesion and retention at sites of cartilage degeneration are critical for improving cartilage repair. This study investigated whether platelet-rich plasma (PRP) enhances the adhesion and short-term retention of bone marrow-derived MSCs (BM-MSCs) and chondrocytes under in vitro and ex vivo conditions. BM-MSCs and chondrocytes were treated with PRP or pretreated with PRP for 10 or 30 min, and cell adhesion to collagen-coated surfaces was evaluated using a cell viability assay. Ex vivo adhesion and short-term retention of BM-MSCs on osteochondral discs with varying lesion severity were assessed by fluorescence imaging analysis. PRP significantly enhanced the adhesion of both BM-MSCs and chondrocytes in a time-dependent manner, with the 30 min PRP pretreatment group showing the greatest effect. BM-MSC attachment in the 30 min PRP pretreatment group was significantly higher than that in the untreated control group after 30 min of incubation (p < 0.001), whereas chondrocyte attachment was also significantly increased following PRP pretreatment. In addition, PRP pretreatment significantly enhanced BM-MSC attachment compared with PRP treatment alone at 20 and 30 min of incubation (both p < 0.001). In ex vivo experiments, adhesion and short-term retention increased significantly with increasing lesion severity from G1 to G3 (p < 0.05 and p < 0.01, respectively). In G2 and G3 lesions, PRP pretreatment for 30 min significantly enhanced BM-MSC adhesion and short-term retention compared with the control group (both p < 0.01). These findings suggest that PRP may improve the early adhesion and retention of MSCs on damaged cartilage and support the potential use of PRP as a biological adjunct for MSC-based cartilage repair strategies. Full article

Tissue engineering using the self-assembly approach represents a promising technology. However, age-related reductions in extracellular matrix deposition by stromal cells limit the mechanical robustness of reconstructed tissues what can be critical for midurethral sling reconstruction. Indeed, stress urinary incontinence predominantly affects women over 50 years of age and is commonly treated by implantation of midurethral slings, whose synthetic versions have raised concerns regarding safety and long-term tolerance. In this study, we investigated whether biochemical modulation could enhance collagen deposition and mechanical properties of self-assembled dermal tissues reconstructed from female donors of different ages. Dermal fibroblasts were cultured in the presence of ascorbic acid, and the effects of hormonal supplementation, metabolic and hypoxia-related stimuli, and insulin signaling activation were evaluated using collagen quantification, histological analyses, and mechanical testing. Fibroblasts derived from younger donors deposited significantly more collagen than those from older female donors. Among all tested conditions, insulin like growth factor 1 (IGF 1) markedly increased collagen deposition in a dose-dependent manner, including in fibroblasts from women over 50 years of age, whereas β-estradiol and progesterone had no significant effect on collagen content. Although β-estradiol slightly increased tissue thickness, only IGF-1 supplementation resulted in substantial improvements in perforation strength, stiffness, displacement at break, and toughness. These results demonstrate that IGF-1 is a potent enhancer of extracellular matrix production and mechanical performance in dermal tissues reconstructed by the self-assembly approach, and represents a promising strategy to improve the development of biological midurethral slings. Full article