Search Results (625)

This study aimed to compare the performance of three hydroxyapatite–β-tricalcium phosphate (HA–β-TCP) collagen composite grafts in a canine model for extraction socket preservation. Eight mongrel dogs underwent atraumatic bilateral mandibular premolar extraction, and sockets were randomly grafted with HBC28 (20% high-crystalline HA, 80% β-TCP bovine collagen), HBC37 (30% HA, 70% β-TCP, bovine collagen), or HPC64 (60% HA, 40% β-TCP, porcine collagen). Grafts differed in their HA–β-TCP ratio and collagen origin and content. Animals were sacrificed at 4 and 12 weeks, and the healing sites were evaluated using micro-computed tomography (micro-CT) and histological analysis. At 12 weeks, all groups showed good socket maintenance with comparable new bone formation. However, histological analysis revealed that HBC28 had significantly higher residual graft volume, while HPC64 demonstrated more extensive graft resorption. Histomorphometric analysis confirmed these findings, with statistically significant differences in residual graft area and bone volume fraction. No inflammatory response or adverse tissue reactions were observed in any group. These results suggest that all three HA–β-TCP collagen composites are biocompatible and suitable for socket preservation, with varying resorption kinetics influenced by graft composition. Selection of graft material may thus be guided by the desired rate of replacement by new bone. Full article

This study evaluated the effects of low-dose recombinant human bone morphogenetic protein-2 (rhBMP-2) coating in combination with vacuum plasma treatment on titanium implants, aiming to enhance osseointegration and bone regeneration while minimizing the adverse effects associated with high-dose rhBMP-2. In vitro analyses demonstrated that plasma treatment increased surface energy, promoting cell adhesion and proliferation. Additionally, it facilitated sustained rhBMP-2 release by enhancing protein binding to the implant surface. In vivo experiments using the four-beagle mandibular defect model were conducted with the following four groups: un-treated implants, rhBMP-2–coated implants, plasma-treated implants, and implants treated with both rhBMP-2 and plasma. Micro-computed tomography (micro-CT) and medical CT analyses revealed a significantly greater volume of newly formed bone in the combined treatment group (p < 0.05). Histological evaluation further confirmed superior outcomes in the combined group, showing significantly higher bone-to-implant contact (BIC), new bone area (NBA), and inter-thread bone density (ITBD) compared to the other groups (p < 0.05). These findings indicate that vacuum plasma treatment enhances the biological efficacy of low-dose rhBMP-2, representing a promising strategy to improve implant integration in compromised conditions. Further studies are warranted to determine the optimal clinical dosage. Full article

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are rare tumors with different clinical and biological characteristics. Ki-67 staining and mitotic counts are the most commonly used prognostic markers, but these methods are time-consuming and lack reproducibility, highlighting the need for innovative approaches that improve histological evaluation and prognosis. In our previous study, we observed that the microRNA (miRNA) expression profile of GEP-NENs correlates with the three grades of GEP-NENs. This study aimed to characterize a group of miRNAs that discriminate well-differentiated GEP-NENs grading 1 (G1) and grading (G2). Fifty formalin-fixed and paraffin-embedded tissue specimens from well-differentiated GEP-NENs G1 and G2 tissues were used for this study. The expression levels of 21 miRNAs were examined using qRT-PCR, while FGFR2 and FGF1 protein expression were evaluated through immunohistochemistry (IHC). We identified four miRNAs (hsa-miR-133, hsa-miR-150-5p, hsa-miR-143-3p and hsa-miR-378a-3p) that are downregulated in G2 GEP-NENs compared to G1. Bioinformatic analysis revealed that these miRNAs play a key role in modulating the FGF/FGFR signaling pathway. Consistent with this observation, we found that fibroblast growth factor receptor 2 (FGFR2) expression is markedly higher in G2 NENs patients, whereas its expression remains low in G1 NENs. Our findings highlight the potential use of miRNAs to confirm the histological evaluation of GEP-NENs by employing them as biomarkers for improving histological evaluation and tumor classification. Full article

Vital pulp therapy with calcium hydroxide or mineral trioxide aggregate (MTA) rapidly induces dystrophic calcification and promotes the accumulation of two members of small integrin-binding ligand N-linked glycoproteins: osteopontin (OPN) and dentin matrix protein-1 (DMP1). However, the precise relationship between these initial events and their roles in reparative dentinogenesis remain unclear. This study aimed to clarify the relationship between dystrophic calcification, OPN and DMP1 accumulation, and reparative dentin formation. Pulpotomy was performed on rat molars using MTA or zirconium oxide (ZrO₂). ZrO₂ was used as a control to assess pulp healing in the absence of dystrophic calcification. Pulpal responses were evaluated from 3 h to 7 days postoperatively via elemental mapping, micro-Raman spectroscopy, and histological staining. In the MTA-treated group, a calcium-rich dystrophic calcification zone containing calcite and hydroxyapatite was observed at 3 h after treatment; OPN and DMP1 accumulated under the dystrophic calcification zone by day 3; reparative dentin formed below the region of OPN and DMP1 accumulation by day 7. In contrast, these reactions did not occur in the ZrO₂-treated group. These results suggest that dystrophic calcification serves as a key trigger for OPN and DMP1 accumulation and plays a pivotal role in reparative dentinogenesis. Full article

Background: This study aimed to develop a nomogram based on the most relevant clinical, CT, and radiomic features comprising 11 key signatures (2 clinical, 2 CT-based, and 7 radiomic) for the non-invasive prediction of the EGFR mutation status and to support the timely initiation of tyrosine kinase inhibitor (TKI) therapy in patients with non-small cell lung cancer (NSCLC) adenocarcinoma. Methods: Retrospective real-world data were collected from 521 patients with histologically confirmed NSCLC adenocarcinoma who underwent CT imaging and either surgical resection or pathological biopsy for EGFR mutation testing. Five Random Forest classification models were developed and trained on various datasets constructed by combining clinical, CT, and radiomic features extracted from CT image regions of interest (ROIs), with and without feature preselection. Results: The model trained exclusively on the most relevant clinical, CT, and radiomic features demonstrated superior predictive performance compared to the other models, with strong discrimination between EGFR-mutant and wild-type cases (AUC = 0.88; macro-average = 0.90; micro-average = 0.89; precision = 0.90; recall = 0.94; F1-score = 0.91; and accuracy = 0.87). Conclusions: A nomogram constructed using a Random Forest model trained solely on the most informative clinical, CT, and radiomic features outperformed alternative approaches in the non-invasive prediction of the EGFR mutation status, offering a promising decision-support tool for precision treatment planning in NSCLC. Full article

Micro-fragmented adipose tissue (MFAT) is a promising autologous therapy for knee osteoarthritis. To avoid repeated liposuction procedures for its clinical application, MFAT obtained from patients with knee osteoarthritis was stored at −80 °C in a tissue bank. This study describes the preparation, cryopreservation, thawing, and washing, as well as comprehensive analysis of cell populations in fresh and MFAT thawed after two years. Immunophenotyping of both fresh and thawed MFAT showed a significant presence of endothelial progenitors and pericytes in the stromal vascular fraction. Viability before (59.75%) and after freezing (55.73%) showed no significant difference. However, the average cell count per gram of MFAT was significantly reduced in thawed samples (3.00 × 10⁵) compared to fresh ones (5.64 × 10⁵), likely due to processing steps. Thawed MFAT samples showed increased CD73 expression on the CD31^highCD34^high subset of EP and SA-ASC, as well as increased expression of CD105 on EP, the CD31^lowCD34^low subset of EP, pericytes, and SA-ASC. Microbiological testing confirmed 100% sterility, and double washing efficiently removed DMSO, confirming sample safety. Histological analysis revealed healthy, uniformly shaped adipocytes with intact membranes. This approach allows accurate estimation of cell yield for intra-articular injection, ensuring delivery of the target cell number into the knee. Quality control analysis confirms that cryopreserved MFAT retains high cellular and structural integrity, supporting its safety and suitability for clinical application. Full article

Periodontitis is a chronic inflammatory disease caused by periodontopathic bacteria such as Porphyromonas gingivalis (P. gingivalis), which leads to alveolar bone destruction and systemic inflammation. Emerging evidence suggests that probiotics may mitigate periodontal pathology. To systematically evaluate the alleviative effects and mechanisms of different forms of probiotics, including live bacteria and postbiotics, on periodontitis, we first screened and identified Ligilactobacillus salivarius CCFM1332 (L. salivarius CCFM1332) through in vitro antibacterial and anti-biofilm activity assays. Subsequently, we investigated its therapeutic potential in a rat model of experimental periodontitis. The results demonstrated that both live L. salivarius CCFM1332 (PL) and its postbiotics (PP) significantly reduced the gingival index (GI) and probing depth (PD) in rats, while suppressing oral colonization of P. gingivalis. Serum pro-inflammatory cytokine levels were differentially modulated: the PL group exhibited reductions in interleukin-17A (IL-17A), interleukin-6 (IL-6), and interleukin-1β (IL-1β) by 39.31% (p < 0.01), 17.26% (p < 0.05), and 14.74% (p < 0.05), respectively, whereas the PP group showed decreases of 34.79% (p < 0.05), 29.85% (p < 0.01), and 19.74% (p < 0.05). Micro-computed tomography (Micro-CT) analysis demonstrated that compared to the periodontitis model group (PM), the PL group significantly reduced alveolar bone loss (ABL) by 30.1% (p < 0.05) and increased bone volume fraction (BV/TV) by 49.5% (p < 0.01). In contrast, while the PP group similarly decreased ABL by 32.7% (p < 0.05), it resulted in a 40.4% improvement in BV/TV (p > 0.05). Histological assessments via hematoxylin and eosin (H&E) and tartrate-resistant acid phosphatase (TRAP) staining confirmed that both the PL group and the PP group alleviated structural damage to alveolar bone-supporting tissues and reduced osteoclast-positive cell counts. This study suggests that live L. salivarius CCFM1332 and its postbiotics reduce alveolar bone resorption and attachment loss in rats through antibacterial and anti-inflammatory pathways, thereby alleviating periodontal inflammation in rats. Full article

The aim of this study was to evaluate structural and micro-architectural changes in the mandible, parietal bone, femur, and tibia in OVX rats at different time periods after ovariectomy. Forty-two 11-month-old female Wistar rats were used. Six rats without surgery were euthanized to serve as a baseline. Eighteen rats were ovariectomized and fed with a calcium-deficient diet, and eighteen animals were used as controls (Ctrls) and fed with a standard diet. Six OVX rats and six Ctrls were euthanized at 3, 6, and 9 months. Qualitative histology and dual-energy X-ray absorptiometry (DXA) were performed. Histological evaluation of bones harvested from the OVX groups revealed trabecular bone reduction, while no significant differences in the cortical bone of OVX and Ctrls were observed. DXA measurements of (1) femoral diaphysis showed a significant decrease in the OVX group compared to the Ctrl groups at 3 (p = 0.041), 6 (p < 0.001), and 9 months (p < 0.001); (2) the proximal tibia showed a significant decrease in the OVX group compared to the Ctrl groups (p < 0.001); (3) parietal bone showed a significant difference between OVX and Ctrls at 6 months (p = 0.012); and (4) the mandible showed no significant differences between the OVX and Ctrl groups. OVX aged rats might present reductions in the density of the femoral diaphysis, proximal tibia, parietal bone, and mandible at different time points. These findings contribute to the field of biomimetics by providing more details for the understanding of age- and hormone-related bone changes in the osteoporotic-like rat model. Such data are critical for the development of biomimetic materials and structures that attempt to simulate natural bone adaptation and deterioration, especially in the context of postmenopausal or osteoporotic conditions. Full article

Living myocardial slices (LMSs) have shown great promise in cardiac research, allowing multicellular and complex interplay analyses with disease and patient specificity, yet their wider clinical use is limited by the large tissue sizes usually required. We therefore produced mini-LMSs (<10 mm²) from routine human cardiac surgery specimens and compared them with medium (10–30 mm²) and large (>30 mm²) slices. Size effects on biomechanical properties were examined with mathematical modeling, and viability, contraction profiles, and histological integrity were followed for 14 days. In total, 34 mini-, 25 medium, and 30 large LMS were maintained viable, the smallest measuring only 2 mm². Peak twitch force proved to be size-independent, whereas time-to-peak shortened as slice area decreased. Downsized LMSs displayed excellent contractile behavior for five to six days, after which a gradual functional decline and micro-architectural changes emerged. These findings confirm, for the first time, that mini-LMSs are feasible and viable, enabling short-term, patient-specific functional studies and pharmacological testing when tissue is scarce. Full article

Background/Objectives: Hypertension is a major contributor to cardiovascular diseases and is often intensified by psychological stress, which can also affect bone metabolism. Although both conditions independently compromise bone health, their combined impact—particularly under acute and chronic stress—remains unclear. This pilot study aimed to assess the effects of such stressors on bone structure in spontaneously hypertensive rats (SHRs). Methods: Forty male rats, both normotensive and SHRs, were randomly assigned to control, acute stress, or chronic stress groups. Acute stress involves a single 2 h physical restraint. Chronic stress was induced over 10 days using alternating stressors: agitation, forced swimming, physical restraint, cold exposure, and water deprivation. Tibial bones were analyzed by microcomputed tomography (micro-CT), and histology was performed using Hematoxylin and Eosin and Masson’s Trichrome stains. Results: Micro-CT showed increased trabecular bone volume in normotensive rats under chronic stress, whereas SHRs displayed impaired remodeling under both stress types. Histological analysis revealed preserved connective tissue overall but evident changes in growth plate structure among stressed rats. SHRs exhibited exacerbated trabecular formation and cartilage abnormalities, including necrotic zones. Conclusions: Both acute and chronic stress, especially in the context of hypertension, negatively affect bone remodeling and maturation. Despite the absence of overt inflammation, structural bone changes were evident, indicating potential long-term risks. These findings highlight the importance of further studies on stress–hypertension interactions in bone health as well as the exploration of therapeutic approaches to mitigate skeletal damage under such conditions. Full article

This study investigated the effects of local fibroblast growth factor (FGF)-2 application on periodontal healing in an osteoporotic model, both in vivo and in vitro. Wistar rats were divided into the ovariectomy (OVX) and Control groups. Periodontal defects were created 8 weeks post-OVX and treated with hydroxypropylcellulose (HPC) or FGF-2 + HPC. Healing was evaluated through micro-computed tomography and histological analyses at 2 and 4 weeks. In vitro, bone marrow mesenchymal stromal cells (BMSCs) were cultured with/without FGF-2 and assessed for cell morphology, viability/proliferation, and osteoblastic marker expression. Alkaline phosphatase (ALP) staining was also performed. FGF-2-treated defects in both groups showed significantly greater bone volume fraction, trabecular number, and thickness compared to HPC only. Histologically, FGF-2 enhanced new bone formation, with the greatest levels in the Control group. In vitro, OVX BMSCs showed reduced actin staining versus controls. FGF-2 increased cell viability/proliferation and protrusions in both groups while downregulating Alpl and Bglap expression levels and reducing ALP-positive cells. FGF-2 increased new bone formation in the OVX group, stimulated proliferation of OVX BMSCs, and modulated their differentiation. FGF-2 could enhance periodontal healing even under osteoporotic conditions, albeit to a lesser extent. Full article

Periodontitis is an inflammatory disease that affects the periodontal supporting tissues. Its cardinal clinical manifestations encompass gingival inflammation, periodontal pocket formation, and alveolar bone resorption. Urolithin A (UA), a gut microbiota-derived metabolite of ellagitannins, is known for its anti-inflammatory and osseous-protective properties. Nonetheless, the impact of UA on periodontitis remains unknown. To investigate the preventive effect of UA, we employed a lipopolysaccharide (LPS)-induced inflammation model in RAW 264.7 mouse macrophages, a receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation model, and a ligature-induced periodontitis model in mice. The expression of inflammatory factors (tumor necrosis factor-α, TNF-α; interleukin-6, IL-6) was analyzed to assess anti-inflammatory efficacy. Bone loss in mice with periodontitis was assessed through histological and imaging techniques, including haematoxylin and eosin staining to evaluate alveolar bone morphology, Masson’s trichrome staining to visualize collagen fiber distribution, and micro-computed tomography scanning to quantify bone structural parameters. Additionally, we investigated the underlying mechanisms by examining osteoclast activity through tartrate-resistant acid phosphatase staining and the expression levels of proteins RANKL and osteoprotegerin (OPG). We found that UA reduced IL-6 and TNF-α levels in vitro and in vivo, inhibited osteoclast differentiation, and decreased the RANKL/OPG ratio in periodontitis mice. Full article

The strategy of active surveillance for papillary thyroid microcarcinoma (PTMC) is becoming increasingly popular within the global medical community. A key criterion for selecting this strategy is the absence of any signs of lymphogenic or distant metastases. The present study assessed the diagnostic accuracy of molecular genetic markers for predicting the metastatic potential of patients with PTMC. We evaluated the expression levels of 33 molecular genetic markers in cytology samples from 92 patients with PTMC and confirmed histological diagnosis. Among these patients, 32 had metastases to regional cervical lymph nodes. Our findings revealed the upregulated expression of the HMGA2, TIMP1, and FN1 genes, as well as microRNA-146b, in patients with metastatic PTMC. Conversely, we found the downregulated expression of miRNA-7 and -148b in metastatic tumors. In metastatic tumors, significant reductions were observed in DIO1 activity (11-fold), TFF3 gene expression (8-fold), TPO expression (4-fold), and SLC26A7 expression (2.6-fold). All the markers exhibited high sensitivity (84.5–90.6%) in detecting metastatic PTMC, although the specificity proved to be low. The use of molecular markers to predict lymphogenic metastatic spread in patients with PTMC could enhance existing risk grading systems. Such assessments can already be applicable at the preoperative stage. Full article

Effective bone tissue regeneration remains pivotal in implant dentistry, particularly for edentulous patients with compromised alveolar bone due to atrophy and sinus pneumatization. Biomaterials are essential for promoting regenerative processes by supporting cellular recruitment, vascularization, and osteogenesis. This study presents the development and characterization of a novel lithography-printed ceramic β-TCP scaffold, with a macro/micro-porous lattice, engineered to optimize osteoconduction and mechanical stability. Morphological, structural, and biomechanical assessments confirmed a reproducible microarchitecture with suitable porosity and load-bearing capacity. The scaffold was also employed for maxillary sinus augmentation, with postoperative evaluation using micro computed tomography, synchrotron imaging, histology, and Fourier Transform Infrared Imaging analysis, demonstrating active bone regeneration, scaffold resorption, and formation of mineralized tissue. Advanced imaging supported by deep learning tools revealed a well-organized osteocyte network and high-quality bone, underscoring the scaffold’s biocompatibility and osteoconductive efficacy. These findings support the application of these 3D-printed β-TCP scaffolds in regenerative dental medicine, facilitating tissue regeneration in complex jawbone deficiencies. Full article

Background/Objectives: Pediatric sarcomas are a biologically diverse group of mesenchymal tumors associated with morbidity due to recurrence, despite aggressive multimodal treatment. Reliable predictors of early recurrence remain limited. This exploratory study aimed to identify clinical features associated with first tumor recurrence using a machine learning approach tailored to low-event settings. Methods: We conducted a retrospective, single-center cohort study of 23 pediatric patients with histologically confirmed sarcoma. Forty-six baseline variables were extracted per patient, including clinical, histological, and comorbidity data. Tumor recurrence was the primary binary endpoint. A LASSO-regularized logistic regression model was developed using leave-one-out cross-validation (LOOCV) to identify the most informative predictors. Dimensionality reduction (PCA) and SHAP-value analyses were used to visualize patient clustering and interpret variable contributions. Results: The model identified a four-variable risk signature comprising histological grade, primary tumor width, arterial hypertension, and extremity localization. Each additional tumor grade or centimeter of width approximately doubled the odds of recurrence (OR 2.18 and 2.04, respectively). Hypertension and limb location were associated with a 1.7 and 1.9 odds ratio of recurrence, respectively. The model achieved a balanced accuracy of 0.61 ± 0.08 and AUROC of 0.47 ± 0.12, reflecting limited discriminative power. PCA mapping revealed distinct outlier patterns correlating with high-risk profiles. Conclusions: Even in a small cohort, classical prognostic markers, such as tumor grade and size, retained predictive relevance, while hypertension emerged as a novel, potentially modifiable cofactor or indicator for recurrence. Although model performance was modest, the findings are hypothesis-generating and warrant validation in larger prospective datasets. Full article