Search Results (757)

Background: While intravenous administration of nanoparticles (NPs) is effective for targeting the lungs and liver, directing them to other organs and tissues remains challenging. Methods: Here, we report alternative administration routes that improve organ-specific accumulation of poly (lactic-co-glycolic acid) (PLGA) NPs (100 nm, negatively charged) loaded with the near-infrared dye Cyanine 7 (Cy7). NP cytotoxicity was evaluated in HEK293, mMSCs, C2C12, L929, and RAW264.7 cells. Hemocompatibility was assessed using WBCs and RBCs. NPs were administered via the tail vein, carotid, renal, and femoral arteries in BALB/c mice. Administration safety was evaluated by laser speckle contrast imaging and histological analysis. NP biodistribution and accumulation were assessed using in vivo and ex vivo fluorescence tomography and confocal microscopy of cryosections. Results: PLGA-Cy7 NPs demonstrate low cytotoxicity even at high doses and exhibit good hemocompatibility. Administration of NPs through the mouse carotid, renal, and femoral arteries significantly increases accumulation in the target ipsilateral brain hemisphere (31.7-fold) and salivary glands (28.3-fold), kidney (13.7-fold), and hind paw (3.6-fold), respectively, compared to intravenous administration. Injection of NPs through arteries supplying the target organs and tissues does not result in significant changes in blood flow, morphological alterations, or irreversible embolization of vessels, provided the procedure is performed correctly and the optimal dosage is used. Conclusions: These results highlight the potential of intra-arterial delivery of NPs for organ-specific drug targeting, underscoring the synergistic impact of advances in materials science, minimally invasive endovascular surgery, and nanomedicine. Full article

Background/Objectives: The prevalence of gastric subepithelial lesions (SELs) is rising. Endoscopic resection (ER) technique provides a minimally invasive alternative to manage gastric SELs. This study aims to evaluate the effectiveness and safety of ER for gastric myogenic tumors, and examine predictors for gastrointestinal stromal tumors (GISTs). Methods: The retrospective study was conducted between 2012 and 2024 at nine tertiary centers in Taiwan. We enrolled patients with endoscopic ultrasound (EUS)-documented gastric myogenic tumors managed by endoscopic muscular dissection (EMD), endoscopic subserosal dissection (ESSD), submucosal tunneling endoscopic resection (STER), and endoscopic full-thickness resection (EFTR). Clinical manifestation, endoscopic features, and outcomes were analyzed. Results: We enrolled 325 patients with 332 lesions [mean EUS size 14.5 mm, 153 (46.1%) leiomyoma, 152 (45.8%) GISTs, 27 (8.1%) other histology]. ER techniques were 193 (58.1%) EMD, 46 (13.9%) ESSD, 28 (8.4%) STER, and 65 (19.6%) EFTR. Technical success, en bloc, and R0 resection rates were 97.0%, 94.3%, and 88.9%, respectively. Twenty-four (9.0%) procedures were shifted to unintentional EFTR, and 21 (6.3%) patients had complications. No recurrence occurred during mean follow-up period of 921.4 days. Two (0.6%) patients died of non-procedure related reasons. Old age, fundus location, heterogeneous echotexture, and exophytic growth pattern were independent risk factors for GIST (all with p < 0.05). Using the above factors, we built a prediction model with sensitivity of 77.0%, specificity of 85.6%, and AUC of 0.8771. Conclusions: ER is an efficient and safe management for gastric myogenic tumors. The histological type could be predicted by demographic characteristics and EUS features. Full article

Background/Objectives: The ineffectiveness of current treatments for glioblastoma underscores the urgent need for effective alternatives. This study aimed to investigate the effectiveness of sodium dichloroacetate (NaDCA) and a sodium valproate NaDCA combination (NaVPA–NaDCA) on formed patients’ primary cell tumors on the chick embryo chorioallantoic membrane (CAM). Methods: Glioblastoma tissue samples were obtained from three patients during tumor surgery. WHO grade IV, IDH wild-type, and a strong positive cytoplasmic GFAP reaction in tumor cells characterized the investigated glioblastoma cases. The tumor cells GBM2-2F, GBM2-3F, and GBM-4M from the patients were examined. Histological examination of tumor invasion into CAM, angiogenesis, and immunohistochemical expression of GFAP-, PCNA-, p53-, EZH2- and vimentin-positive cells were examined. Results: No difference in GFAP expression was observed between the patient’s GBM tumor tissue and the tumor formed on CAM from the same patient’s tumor cells. There were no significant differences in invasion or in the frequency of GFAP- and p53-positive cells among the study control groups. The expression of PCNA-, EZH2-, and vimentin-positive cells in control tumors varied significantly. Treatment significantly reduced the incidence of tumor invasion in GBM2-2F and GBM2-4M and did not affect GBM2-3F tumors; treatment also significantly reduced GFAP expression in GBM2-3F and GBM2-4M and did not affect GBM2-2F tumors. The treatment with NaVPA–NaDCA significantly reduced the expression of PCNA, p53, EZH2 and vimentin in the tested tumors. Conclusions: Data demonstrated an antitumor effect of NaVPA–NaDCA in an in vivo model of a patient’s primary glioblastoma cells. Full article

Background: Otitis media with effusion (OME) is a widespread condition that causes hearing impairment, particularly in pediatric populations. Existing non-absorbable tubes often require elective or unplanned removal surgery. Bioabsorbable polylactic acid (PLA) offers a promising alternative due to its inherent biocompatibility and tunable degradation characteristics. In this study, we designed, fabricated, and comprehensively evaluated a novel PLA middle-ear ventilation tube. Methods: Bioabsorbable PLA tubes were designed and fabricated based on commercial models. In vitro biocompatibility was assessed according to ISO 10993 guidelines. A guinea pig model was used to perform in vivo evaluations, including otoscopic examinations, auditory brainstem response (ABR) measurements, micro-computed tomography (micro-CT) imaging, and histological analyses. Results: The PLA tubes were successfully designed and fabricated, exhibiting dimensions comparable to those of commercially available products. In vitro testing confirmed their biocompatibility. In vivo observations revealed that the PLA segments remained stable, with no significant inflammation detected. ABR measurements revealed no adverse impacts on hearing function. Micro-CT imaging confirmed tube integrity and indicated initial signs of degradation over a 9-month period, as evidenced by radiographic morphology. Histological analyses indicated a favorable tissue response with minimal foreign body reaction. Conclusions: The developed PLA middle-ear ventilation tube represents a highly promising alternative to conventional non-absorbable tubes. It demonstrates excellent biocompatibility, preserves auditory function, and exhibits a controlled degradation profile. This preclinical study provides strong support for further investigation and subsequent clinical trials to validate its safety and efficacy in human patients. Full article

Peripheral nerve repair remains a major clinical challenge, and novel strategies such as conduit-assisted repair have been developed to improve outcomes. In this study, we fabricated a 3D-printed nerve guidance conduit (NGC) composed of polycaprolactone (PCL), a biocompatible and biodegradable polymer, combined with acellular dermal matrix (ADM) derived from porcine dermis, in order to create a multilayered PCL–ADM NGC with both favorable mechanical properties and biological activity. Twenty rabbits were divided into four groups: a negative control group, a silicone tube repair group, an autologous nerve graft group, and a group treated with the 3D-printed PCL–ADM NGCs. Sciatic nerve regeneration was assessed at 4 and 12 weeks postoperatively using electrophysiological measurements, histological staining, and electron microscopy. The PCL–ADM NGC demonstrated comparable axonal regeneration and functional recovery to autologous grafting, and it significantly outperformed silicone tubes in terms of axonal count and maximal electrophysiological response. Histological and ultrastructural analyses further confirmed that the PCL–ADM NGC facilitated organized regeneration with dense myelinated axons and reduced degenerative changes. The fabricated NGCs exhibited excellent flexibility without compromising lumen diameter, which is critical for adapting to the physiological environment of peripheral nerves. These findings indicate that combining synthetic polymers with biologically derived matrices can enhance the regenerative microenvironment and overcome limitations of traditional synthetic conduits. In conclusion, the 3D-printed PCL–ADM NGC represents a promising alternative to both silicone tube repair and autologous nerve grafting by providing structural support and bioactivity while reducing the need for donor nerve harvesting. Further studies in larger animal models and longer follow-up periods will be required to confirm long-term efficacy and support clinical translation of this technology. Full article

Whole-slide histology images (WSIs) can exceed 100 k × 100 k pixels, making direct pixel-level segmentation infeasible and requiring patch-level classification as a practical alternative for downstream WSI segmentation. However, most approaches either treat patches independently, ignoring spatial and biological context, or rely on deep graph models prone to oversmoothing and loss of local tissue detail. We present WSI-GT (Pseudo-Label Guided Graph Transformer), a simple yet effective architecture that addresses these challenges and enables accurate WSI-level tissue segmentation. WSI-GT combines a lightweight local graph convolution block for neighborhood feature aggregation with a pseudo-label guided attention mechanism that preserves intra-class variability and mitigates oversmoothing. To cope with sparse annotations, we introduce an area-weighted sampling strategy that balances class representation while maintaining tissue topology. WSI-GT achieves a Macro F1 of 0.95 on PATH-DT-MSU WSS2v2, improving by up to 3 percentage points over patch-based CNNs and by about 2 points over strong graph baselines. It further generalizes well to the Placenta benchmark and standard graph node classification datasets, highlighting both clinical relevance and broader applicability. These results position WSI-GT as a practical and scalable solution for graph-based learning on extremely large images and for generating clinically meaningful WSI segmentations. Full article

Rodents models of myocardial infarction (MI) continue to be frequently used in preclinical cardiovascular research, despite alternative approaches being on the rise. The commonly used coronary artery permanent ligation (PL) approach is often hampered by substantial perioperative mortality and variable success rates. We optimized the rat PL protocol by relying exclusively on isoflurane inhalation anesthesia by introducing a standardized intubation setup, maintaining strict control of body temperature throughout surgery, and surgical technique refinements. The latter included gentle mobilization of the Pectoralis major and thymus, a medial thoracotomy through the third intercostal space, and the use of a reference ligature to facilitate reliable identification and ligation of the left anterior descending coronary artery (LAD). Cardiac rhythm was continuously monitored, and extubation was carefully timed to reduce complications. With this protocol, perioperative mortality was reduced to zero and successful ligation was obtained in 94% of animals (n = 172). Echocardiography and histology confirmed consistent induction of infarcts. By lowering invasiveness and improving survival and reproducibility, the refined PL method enhances both the reliability of preclinical research and compliance with the 3Rs, representing a meaningful step forward for studies in cardiac regeneration. Full article

Extramammary Paget’s disease (EMPD) is a rare cutaneous adenocarcinoma typically arising on apocrine gland-rich skin. This suprapubic location is exceptionally rare. Its nonspecific erythematous plaques often mimic benign inflammatory or infectious dermatoses, delaying diagnosis. We report an 80-year-old male who presented with a chronic suprapubic plaque. Videodermoscopy and line-field confocal optical coherence tomography (LC-OCT) highlighted irregular vascular patterns and pagetoid cells, raising suspicion for EMPD and guiding a biopsy. Histopathology confirmed carcinoma in situ, and immunostains (CK7 positive, CK20 negative) supported a primary cutaneous origin. Comprehensive screening ruled out associated malignancies; however, guidelines note that colon, rectal, prostate, and bladder cancers are the most frequent synchronous tumors and suggest considering tailored internal malignancy screening. Wide local excision achieved clear margins; after one year, there is no recurrence. The literature indicates that recurrence remains frequent after surgery and may not correlate with margin width, necessitating careful long-term surveillance. For patients unfit for surgery, alternative therapies include radiotherapy, topical imiquimod, and photodynamic therapy, though photodynamic therapy appears palliative rather than curative. Non-invasive imaging modalities, such as LC-OCT, provide high-resolution “virtual histology,” enhancing early diagnosis and reducing the need for repeated biopsies. Early recognition, appropriate staging, and multidisciplinary management are crucial for improving outcomes. Full article

Directional asymmetry (DA) is a widespread yet often overlooked feature of animal morphology. Here, we report a consistent right-biassed asymmetry in the crystalline lenses of the thornback ray Raja clavata. Across 71 individuals sampled from the Strait of Sicily, 24% exhibited lens asymmetry, and in all cases, the right lens was larger. This pattern, supported by binomial and distributional tests, represents the first evidence of ocular DA in this species. Body size and age emerged as the primary correlates of asymmetry: the odds of exhibiting DA increased significantly with body weight, whereas the effects of sex and sampling site were not significant. The prevalence of asymmetry thus appears to rise with age and ontogenetic growth. Two non-exclusive mechanisms may account for this pattern. First, the association with positive allometry (b = 3.33) suggests that right-lens enlargement could reflect a functional or developmental lateralisation, potentially conferring a visual or ecological advantage to larger individuals. Alternatively, the same right-lens bias could arise through an age-related pathological process, such as oxidative or osmotic lens swelling preceding cataract formation, consistent with asymmetric physiological wear. These findings reveal a novel case of morphological lateralisation in an elasmobranch and highlight the need for comparative, histological, and functional approaches to disentangle adaptive asymmetry from lateralised senescence in the visual system of R. clavata. Full article

Background: Arterial hypertension (AH) remains a global health concern due to its multifactorial etiology, limited therapeutic success, and high cardiovascular risk. In this context, plant-derived compounds such as essential oils have gained attention as alternative strategies. The monoterpene (-)-linalool (LIN) demonstrates antihypertensive effects. However, its clinical application is hampered by poor solubility and low bioavailability. Methods: This study aimed to investigate the chronic cardiovascular effects of free LIN and its inclusion complex with β-cyclodextrin (LIN/β-CD) in spontaneously hypertensive rats (SHR) and normotensive Wistar rats. Results: Pharmacokinetic analysis showed that complexation with β-CD markedly improved LIN plasma exposure, increasing systemic bioavailability by approximately 20-fold and prolonging its circulation time. In acute assays, intravenous LIN and LIN/β-CD (50 mg/kg) reduced blood pressure in SHR, LIN induced bradycardia, and LIN/β-CD elicited a mild, non-significant tachycardia. Orally administered LIN/β-CD exerted superior antihypertensive effects compared to free LIN. In a 60-day chronic regimen, LIN/β-CD consistently maintained reduced arterial pressure, achieving levels comparable to normotensive controls, while free LIN produced transient effects. LIN/β-CD also significantly reduced the cardiac mass index in SHR, suggesting attenuation of hypertrophic remodeling. Vascular reactivity assays revealed enhanced endothelium-dependent and -independent relaxation and diminished vasoconstriction in LIN/β-CD-treated animals, indicating improved endothelial and smooth muscle function. Histological analyses confirmed the absence of cardiac or vascular injury in both treatment groups. Conclusions: In conclusion, the LIN/β-CD complex improves the pharmacokinetic profile and enhances the arterial morphology, antihypertensive and cardioprotective effects of linalool. These findings support its translational potential as a safe and effective oral formulation for the long-term management of hypertension and associated cardiovascular dysfunction. Full article

Current tumor diagnostics rely on fluorodeoxyglucose (FDG)-PET imaging, but FDG’s short half-life and high cost limit its widespread use. Infrared (IR) probes are emerging as non-radioactive alternatives to conventional tracers for tissue section and other in vitro imaging applications. Because cells and tissues are relatively free of absorption peaks between 1800 and 2200 cm⁻¹, metal-carbonyl complexes, especially cyclopentadienylrhenium(I) tricarbonyl (Cp[Re(CO)₃]) derivatives, absorb strongly in this window and provide robust platforms for bioconjugation. Furthermore, Cp[Re(CO)₃] fragments can be introduced into organic substrates via an elegant three-component reaction that simultaneously forges the cyclopentadienyl-metal and cyclopentadienyl-substituent bonds. As a result, the functionalized half-sandwich complex is obtained in a single step without any special handling issues. We have therefore properly modified a glucose molecule with that complex and developed a novel glucoconjugated Cp[Re(CO)₃] probe that enables IR-based visualization of diseased cells at 2100 cm⁻¹, offering a non-invasive, non-radioactive histological tool and a promising basis for future medical imaging devices. Full article

Background/Objectives: The zebrafish is a widely used research model due to its characteristics, such as being transparent during development, sharing 70% of its genes with humans, and having conserved features of vertebrate aging, including deterioration of mitochondrial and cognitive functions. While affecting approximately 15% of the world population, neurodegenerative diseases, such as Alzheimer’s disease (AD), are currently incurable, requiring testing of alternative treatment strategies. Hence, this study was conducted to test the hypothesis that an optimized photobiomodulation (PBM) therapy improves AD pathology through its multifaceted beneficial effects, including enhancing mitochondrial function and reducing oxidative stress and neuroinflammation. Methods: A pharmacological zebrafish model of AD was developed by adding small amounts (100 nM) of okadaic acid (OKA) directly to fish tanks for nine days. Next, some of OKA-treated and control zebrafish were subjected to an optimized near-infrared PBM therapy while others remain untreated. Results: When examined after OKA treatment, zebrafish brains displayed histological hallmarks of AD including, neurofibrillary tangles, vacuoles, and neuroinflammation. Behavioral tests using a T-maze revealed that OKA-treated zebrafish spent significantly less time in the reward arm than untreated controls (15.2% vs. 50%). In contrast, a sequential PBM therapy significantly reduced formation of neurofibrillary tangles, vacuoles, neuroinflammation, and improved mitochondrial biogenesis in brains of OKA-treated zebrafish while also improving their cognitive function as evidenced by being able to recall the reward arm and spending more time there similar to controls (55 and 57%, respectively). Conclusions: These findings suggest that (1) a fast, cost-effective zebrafish AD model can be developed using OKA treatment and (2) PBM therapy holds promise to ameliorate AD pathology. Full article

Background: With the rising incidence of cancer, there is a growing need for improved preclinical models to test new therapies. While patient-derived xenografts (PDX) in immunodeficient mice are the gold standard, they are costly and result in a complete absence of a functional immune system, limiting their utility for studying tumor–immune interactions. This study characterizes a pharmacological partial immunosuppression protocol in immunocompetent mice as a promising alternative, evaluating its impact on the immune system and demonstrating its efficacy for growing human tumor xenografts. Methods: Mice received a regimen of cyclosporine (20 mg/kg, i.p., every 48 h for 12 days), cyclophosphamide (60 mg/kg, i.p., every 48 h for 8 days), and ketoconazole (10 mg/kg, p.o., for 12 days). The dynamics of CD3⁺, CD4⁺, CD8⁺, and CD19⁺ lymphocyte subpopulations and the CD4/CD8 index were monitored via flow cytometry on days 1, 5, 8, 12, 16, and 21. The protocol’s utility was tested by orthotopic transplantation of human glioma and lung cancer cells, and subcutaneous transplantation of breast cancer cells (MCF7). Tumor engraftment and growth were assessed using in vivo microscopy, MRI, and histology. Results: The immunosuppressive protocol induced a significant but partial reduction in CD3⁺ T-cells and CD19⁺ B-cells by day 8 (p = 0.0277). A profound and progressive decrease in the CD4/CD8 index was observed, indicating a shift towards immunosuppression. Crucially, CD8⁺ and CD4⁺ T-cells populations recovered rapidly post-therapy, demonstrating that the protocol creates a temporary and modifiable immune window rather than inducing complete ablation. The protocol enabled successful engraftment and growth of all three tested tumors in a residual immune microenvironment, confirmed by in vivo imaging and histopathological analysis. Conclusions: This drug-induced partial immunosuppression protocol effectively creates a reproducible state of transient immunodeficiency in outbred mice, suitable for various human tumor xenograft models. It represents a cost-effective and flexible alternative to genetic models, with the distinct advantage of preserving a residual immune microenvironment, making it particularly valuable for preclinical studies that require a partially intact host immune system. Full article

The repair of large segmental bone defects remains a major clinical challenge. Traditional bone repair materials often suffer from mismatched degradation rates, insufficient mechanical strength, or limited bioactivity. Biodegradable zinc alloys have emerged as potential alternatives due to their suitable degradation rate and good biocompatibility, though their bioactivity requires further enhancement. In this study, a zinc phosphate (ZnP) coating was applied on the surface of zinc–copper (Zn–Cu) alloy via a phosphate chemical conversion method, and the corrosion resistance, wear resistance, and osteogenic properties of the coating were systematically evaluated. Results showed that the ZnP coating prepared at pH = 2.5 exhibited a dense structure and high crystallinity, reducing the corrosion rate to 0.010 μm/year and increasing the ultimate tensile strength to 117.03 ± 0.78 MPa, significantly improving the wear and corrosion resistance of the alloy. In vivo experiments demonstrated that the material markedly promoted new bone formation and osseointegration. Micro-computed tomography (Micro-CT) revealed that key indicators such as bone volume fraction (approximately 50.26%) and trabecular number (approximately 161.31/mm³) were superior to those of the β-tricalcium phosphate (β-TCP) group and the control group. Histological analysis confirmed its excellent osteogenic activity and mineralization capacity. Biosafety assessments indicated no systemic toxic reactions. The ZnP-coated Zn-1Cu alloy showed promising application in treatment of bone defect. Full article

Background: Practical, quantitative ultrasound-based tools for measuring hepatic steatosis are needed in everyday MASLD care. We evaluated a new multiparametric quantitative ultrasound (QUS) platform that integrates ultrasound-guided fat fraction (UGFF), attenuation coefficient (AC), backscatter coefficient (BSC), and signal-to-noise ratio (SNR), using Controlled Attenuation Parameter (CAP) as the reference and examining the effect of breathing. Methods: In a prospective single-center study, adult patients underwent same-day liver QUS and FibroScan. QUS measurements were performed during breath-hold and during normal breathing. Regions of interest were placed in right-lobe parenchyma 2 cm below the capsule, avoiding vessels. Primary outcomes were correlation with CAP and ROC performance at CAP cutoffs for S1 (≥230 dB/m), S2 (≥275 dB/m), and S3 (≥300 dB/m). Results: QUS was feasible in almost all examinations. UGFF, BSC, and SNR were consistent across breathing conditions, while AC was slightly higher during normal breathing. UGFF showed strong correlation with CAP and high accuracy for detecting steatosis. Across grades, AUCs were around 0.89–0.91, with cutoffs (UGFF ≈ 4% for ≥S1 and ≈11% for ≥S3). Conclusions: Multiparametric QUS provides reliable liver fat quantification that aligns closely with CAP and remains robust in practice whether patients hold their breath or breathe normally. These findings support UGFF as a practical, reliable point-of-care alternative for liver fat quantification that can be embedded in routine ultrasound in real time. Validation against MRI-PDFF or histology and multicenter studies will further define cutoffs and generalizability. Full article