Search Results (5,509)

Although extracellular vesicles (EVs) from mesenchymal stem cells have shown potential in skin wound repair, the diversity of EV sources and the optimization of delivery systems still need further exploration. This study is the first to demonstrate that extracellular vesicles from chemically induced mammary epithelial cells (CiMECs-EVs) possess distinct skin wound repair activity. To enhance the therapeutic efficacy of CiMECs-EVs and optimize their delivery efficiency, we innovatively combined them with a chitosan hydrogel to construct a composite repair system (CiMECs-EVs-chitosan hydrogel, CMECG). This system was then applied to a rat skin wound model. The results showed that CMECG significantly promoted the proliferation and migration of fibroblasts and mammary epithelial cells (MECs). In animal experiments, the relative wound closure efficiency of the control group was approximately 70% on day 14, while that of the CMECG group (loaded with 200 μg CiMECs-Exo) was enhanced to 90%, markedly accelerating the wound healing process. Histological analysis indicated that this system could effectively restore the structural continuity of various skin layers and significantly promote the synthesis and remodeling of collagen at the wound site. Mechanistically, the wound healing effect of CiMECs-EVs is closely associated with the endogenous miRNAs they encapsulate. These miRNAs can coordinately regulate cell proliferation, migration, and angiogenesis, modulate the inflammatory microenvironment, and inhibit excessive scar formation—thus regulating the entire repair process. This process involves multiple wound healing-related signaling pathways, including MAPK, PI3K-Akt, FoxO, TGF-β, and JAK-STAT. In summary, this study successfully constructed a novel EV-chitosan hydrogel repair system. This system is expected to provide an effective and innovative EV-based therapeutic strategy for the clinical treatment of skin wound repair. Full article

Background/Objectives: Colorectal cancer (CRC) is a leading cause of cancer-related morbidity and mortality worldwide. This study evaluates the predictive value of Carcinoembryonic Antigen (CEA) in identifying CRC recurrence following surgical resection. Methods: This retrospective study was realized in the Oncology Institute in Cluj-Napoca and included 88 patients diagnosed with CRC. Clinical, demographic, and tumor-specific data were collected, including TNM staging, tumor histology. CEA levels were recorded before surgery. Receiver Operating Characteristic (ROC) analysis was performed to determine the diagnostic accuracy of CEA in predicting tumor relapse, and the sensitivity and specificity of various CEA cut-off values were assessed. Results: Most patients presented with advanced-stage tumors (T3/T4, 80.6%). CEA levels were significantly higher in patients with lymphatic and perineural invasion and in those with metastases (mean CEA: 45.0 ng/mL for M1 vs. 13.2 ng/mL for M0, p = 0.032). ROC analysis revealed an area under the curve (AUC) of 0.877 (95% CI: 0.763–0.949). A CEA cut-off value of 11.73 ng/mL yielded 100% sensitivity and 74.5% specificity for detecting recurrence; Conclusions: CEA is a valuable non-invasive biomarker for predicting CRC relapse, with high sensitivity and acceptable specificity. Regular CEA monitoring post-surgery can facilitate early detection of recurrence, improving prognosis. Full article

Saline–alkaline soils are becoming prevalent across the globe, decreasing the availability of forage for animals and threatening sustainable animal production. This study evaluated the effects of a NaCl-supplemented alfalfa-based total mixed ration, simulating saline–alkaline soil conditions, on intake, the utilization of nutrients, antioxidant levels, and rumen fermentation. A 60-day feeding trial with 24 AOHU lambs (Australian White × Hu) compared a control diet (0.43% NaCl) with the NaCl-supplemented group (1.71% NaCl). Digestibility trials were conducted in metabolic cages for the collection of total feces and urine. Blood samples were taken at 0, 30, and 60 days for serum analysis, and slaughter samples (liver, kidney, rumen tissue, and rumen fluid) were taken for physiological, biochemical, and histological evaluation. The NaCl alfalfa-based TMR markedly increased liver and kidney weights. The rumen muscle layer thickened in the NaCl group. The ruminal ammonia nitrogen (NH₃-N), ruminal microbial crude protein (MCP) synthesis, and glucogenic/branched-chain VFAs increased, indicating enhanced proteolysis, microbial protein synthesis, and energetically efficient fermentation. Serum total protein and albumin also rose over time in the NaCl group, reflecting increased nitrogen retention, while superoxide dismutase and glutathione peroxidase activity rose considerably by day 60, reflecting increased antioxidant defense. Furthermore, nitrogen intake, digestibility, and retention were improved in the NaCl group along with augmented digestible and metabolizable energy (28.47 vs. 13.93 MJ/d and 24.68 vs. 11.58 MJ/d, respectively) and gross energy digestibility (78.13% vs. 67.10%). Although NaCl-based alfalfa TMR cannot fully emulate naturally salt-stressed forages, these results indicate that the NaCl alfalfa-based diets improved rumen fermentation, energy yields, and antioxidant enzyme activity without impairing electrolyte balance. These findings suggest that NaCl-supplemented alfalfa-based TMRs, with a salt content comparable to that of alfalfa hay grown under saline–alkaline conditions, could support environmentally sustainable meat production in salt-stressed regions. Full article

Background: Pancreatic ductal adenocarcinoma (PDAC) is characterized by its aggressive clinical behavior and intricate microenvironment regulation, leading to dismal prognosis. Elucidating the molecular mechanisms underlying PDAC pathogenesis is crucial for developing improved therapeutic approaches. The functional significance and molecular basis of transcobalamin 1 (TCN1) in PDAC remain largely unexplored. Methods and Results: Through integrated analysis of TCGA and GTEx datasets combined with 80 clinical specimens, we identified significant TCN1 overexpression in PDAC, showing a positive association with tumor stage and negative associations with histological differentiation and overall survival. Functional investigations showed that TCN1 enhanced pancreatic cancer cell proliferation, migration, invasion, and epithelial–mesenchymal transition (EMT) in both in vitro and in vivo models. Mechanistically, TCN1 physically interacts with signal transducer and activator of transcription 4 (STAT4) to enhance its transcriptional activity. Chromatin immunoprecipitation (ChIP) assays showed that STAT4-mediated transcriptional activation of dual oxidase 2 (DUOX2) occurs through direct promoter binding. As a pivotal reactive oxygen species (ROS)-generating enzyme, DUOX2 overexpression elevates intracellular ROS levels, thereby promoting EMT progression and activating proliferation-related signaling cascades. Antioxidant treatment effectively abrogated TCN1-driven oncogenic phenotypes, establishing ROS as the critical downstream mediator. Conclusions: Collectively, our findings reveal a novel TCN1/STAT4/DUOX2 regulatory axis that exacerbates PDAC progression by remodeling redox homeostasis. This signaling cascade may serve as a prognostic biomarker and a potential therapeutic target for ROS-directed precision therapy in PDAC. Full article

Background/Objectives: To evaluate whether incorporating both diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) in pituitary MRI examinations improves differential diagnosis by providing additional diagnostic value. Methods: A retrospective analysis was performed on 88 patients with histologically confirmed sellar or parasellar tumors who underwent 1.5T MRI with DWI and dynamic susceptibility contrast PWI (DSC-PWI) between October 2007 and April 2023. DWI parameters included minimum apparent diffusion coefficient (ADCmin) and relative ADCmin (rADCmin). PWI parameters included mean and maximum relative cerebral blood volume (rCBV, rCBVmax) and relative peak height (rPH, rPHmax), normalized to white matter. Tumor regions of interest were manually segmented, excluding calcified or hemorrhagic areas. Group comparisons and ROC analyses assessed diagnostic performance of individual and combined parameters. Results: Significant differences in diffusion and perfusion metrics were observed among the five tumor types. The combined analysis of DWI and PWI improved diagnostic accuracy in selected comparisons. The greatest benefit occurred in distinguishing meningiomas from solid non-functional pituitary adenomas (pituitary neuroendocrine tumors-PitNET), where the combination of ADCmin and rPHmax yielded an AUC of 0.818, sensitivity of 88%, and specificity of 76%, exceeding the performance of either parameter alone. In other comparisons, including meningiomas versus invasive PitNETs and adamantinomatous craniopharyngiomas, combined analysis did not substantially improve accuracy when single parameters, particularly rCBVmax (AUC = 0.995), already demonstrated excellent performance. Conclusions: Integration of DWI and PWI into pituitary MRI protocols enhances diagnostic performance in selected tumor groups. The additive value is context-dependent, supporting the tailored application of these sequences in the evaluation of sellar and parasellar tumors. Full article

Background and Objectives: Minimally invasive surgery is considered the standard of care for early-stage endometrial cancer. However, the oncological safety of intrauterine manipulator (IUM) use during laparoscopic hysterectomy remains controversial. The aim of this study was to evaluate the impact of intrauterine manipulator use during laparoscopic hysterectomy on oncological outcomes in patients with clinically early-stage endometrial cancer. Materials and Methods: In this retrospective cohort study, 612 patients with FIGO 2009 stage I–III endometrial cancer who underwent staging surgery at a tertiary center between January 2010 and May 2025 were included. Clinical and pathological characteristics were compared between laparoscopy (n = 168) and laparotomy (n = 444). To reduce selection bias, propensity score matching (PSM) was performed based on age, histological subtype, and FIGO stage. Kaplan–Meier survival analysis and Cox regression modeling were utilized to evaluate disease-free survival (DFS) and overall survival (OS). Results: After matching, groups were balanced except for higher rates of para-aortic lymphadenectomy and adjuvant therapy in the laparotomy group. IUM use was not associated with increased LVSI or positive peritoneal cytology. Recurrence was more frequent after laparoscopy (10.1% vs. 6.0%, p = 0.028), with inferior 5-year DFS (87.6% vs. 97.4%, HR 5.60, p = 0.0006), while OS was similar (82.0% vs. 87.6%, p = 0.842). In multivariate Cox analysis, independent predictors of worse DFS were non-endometrioid histology (HR 3.57), FIGO stage III (HR 3.06), grade 3 tumors (HR 2.63), and laparoscopic surgery (HR 0.51). For OS, non-endometrioid histology (HR 5.12), stage III disease (HR 2.98), and grade 3 tumors (HR 4.51) were independent adverse factors, whereas surgical approach was not. Conclusions: The use of an intrauterine manipulator in laparoscopic hysterectomy for early-stage endometrial cancer was linked to worse DFS but not OS. These findings suggest caution regarding the routine use of IUMs and highlight the need for prospective randomized trials to clarify their oncological safety. Full article

Background/Objectives: Solitary plasmacytoma of bone (SPB) results from abnormal proliferation of plasma cells and accounts for 2–5% of all plasmacytic malignancies. Radiation therapy is the standard of care in treating SPB due to its efficacy in controlling disease progression and optimizing patient survival. However, prior studies have highlighted disparities in radiation therapy receipt among various cancer types. In this study, we aim to investigate whether similar sociodemographic and clinical disparities exist in the treatment of SPB through use of the Surveillance, Epidemiology, and End Results (SEER) database. Methods: The SEER database was queried for biopsy-confirmed cases of SPB between 2000 and 2021 using the ICD-O-3 histology code 9731/3 and primary site codes C40.0–41.9. Chi-square tests, Fisher’s exact tests, and multivariable logistic regression were completed using SPSS v29.0.2, with significance set to p < 0.05. Results: A total of 4139 patients were identified, of which 75.3% received treatment with radiation therapy. Multivariable analysis revealed that low-income patients making less than $74,999 annually (aOR 0.80, 95% CI 0.67–0.97), as well as those from non-Hispanic Asian/Pacific Islander (aOR 0.49, 95% CI 0.33–0.73) and Hispanic (aOR 0.77, 95% CI 0.60–0.98) racial and ethnic groups, were significantly less likely to receive radiation therapy. Conclusions: These findings reveal notable disparities in radiation therapy utilization for SPB patients based on income and race and ethnicity, emphasizing the need for interventions to address systemic inequities, improve access to care, and ensure that all patients receive high-quality cancer care to optimize long-term outcomes. Full article

Introduction: The 9th edition of the TNM classification for lung cancer implemented significant revisions, notably the subdivision of the N2 and M1c categories, to enhance anatomical precision and prognostic accuracy. Nonetheless, the actual effects of these modifications on stage distribution, histology-specific patterns, and clinical interpretation remain to be fully evaluated. Objectives: To compare lung cancer staging distributions between the 8th and 9th TNM editions, analyze patterns of stage migration, and evaluate histology-specific reclassification trends. Although TNM 9 applies the same descriptors across all histological subtypes, the magnitude of stage migration varies. In our cohort and in international datasets, adenocarcinoma demonstrated a higher likelihood of reclassification into advanced stages compared to other subtypes. Methods: A retrospective analysis was performed on a cohort of lung cancer patients staged according to the 8th and 9th editions of the TNM classification. Stage distribution alterations were analyzed by chi-squared tests, whereas McNemar’s test examined the directional shifts in upstaging and downstaging. Further investigations evaluated the correlation between histological subtype and stage reclassification. Results: A statistically significant redistribution of stages was noted (χ² = 1013.03, df = 64, p < 0.0001), with a notable prevalence of upstaging (p = 0.0019). The most significant proportional increase was observed in stage IIIA, mostly attributable to the N2 subdivision (N2a vs. N2b). Adenocarcinoma was the predominant histological subtype at all stages and showed a greater tendency for reclassification into advanced stages, specifically IIIA and IIIB. Squamous cell carcinoma was predominantly observed in stages IIB and IIIA, whereas small cell and large cell carcinomas were concentrated in advanced stages. These histology-specific patterns correspond with international findings, including research confirming the prognostic relevance of N2 subdivision. Conclusions: The 9th edition of the TNM classification results in significant stage migration, particularly in adenocarcinoma cases, indicating the improved sensitivity of the updated criteria in identifying advanced nodal disease. These modifications significantly impact prognostic evaluation and global comparability of clinical cohorts, supporting the implementation of TNM 9 as a more anatomically and biologically relevant staging system. Full article

Background/Objectives: High-frequency ultrasonography (HFUS) has gained increasing attention in dermatology as a non-invasive imaging technique capable of visualizing cutaneous structures with high resolution. In cutaneous T-cell lymphomas (CTCL), including mycosis fungoides (MF)/Sézary syndrome (SS), HFUS may provide an objective method for assessing disease activity and monitoring treatment response. This study aimed to evaluate the clinical utility of HFUS in detecting therapy-induced changes in subepidermal low-echogenic band (SLEB) thickness. Methods: We conducted a prospective, single-center study between May 2021 and May 2025. Thirty-three patients with histologically confirmed MF (n = 31) or SS (n = 2) underwent HFUS at baseline and after 4–8 weeks of treatment. SLEB thickness was measured before (E1) and after early treatment (E2). Patients received systemic agents, phototherapy, or topical regimens. Statistical analysis included mixed-model ANOVA with repeated measures to assess SLEB changes, and post hoc tests were applied to explore the influence of therapy type, age, and gender. Results: Among 31 evaluable patients with MF, HFUS revealed a significant reduction in SLEB thickness after treatment (0.90 ± 1.10 mm vs. 0.69 ± 0.89 mm; F(1,29) = 8.88, p = 0.006, η² = 0.23). The type of early therapy (systemic vs. topical) did not significantly affect outcomes (p = 0.452). Age emerged as a relevant factor: patients ≥ 66 years exhibited higher baseline SLEB values and a significant reduction post-treatment (p < 0.001), whereas no comparable effect was observed in younger patients. Gender did not significantly influence SLEB changes. Conclusions: HFUS is a sensitive and clinically applicable imaging tool for monitoring treatment response in MF/SS. Reductions in SLEB thickness were observed across therapeutic modalities and aligned with early clinical improvement. HFUS may serve as a valuable adjunct to standard clinical and histopathological evaluation in the routine management of MF/SS. Full article

Small-diameter vascular grafts often fail due to thrombosis and compliance mismatch. Decellularized plant scaffolds are a biocompatible, sustainable alternative. Leatherleaf viburnum leaves provide natural architecture and mechanical integrity suitable for tissue-engineered vessels. However, the persistence of immunogenic plant biomolecules and limited degradability remain barriers to clinical use. This study tested whether mild heat treatment improves scaffold biocompatibility without compromising mechanical performance. Decellularized leatherleaf viburnum scaffolds were treated at 30–40 °C in 5% NaOH for 15–60 min and then evaluated via tensile testing, burst pressure analysis, scanning electron microscopy, histology, and in vitro assays with white blood cells and endothelial cells. Scaffold properties were compared to those of untreated controls. Heat treatment did not significantly affect scaffold thickness but decreased fiber area fraction and diameter across all anatomical layers. Scaffolds treated at 30–35 °C for ≤30 min retained >90% of tensile strength and achieved burst pressures ≥820 mmHg, exceeding physiological arterial pressures. Heat treatment reduced surface fractal dimension while increasing entropy and lacunarity, producing a smoother but more heterogeneous microarchitecture. White blood cell viability increased up to 2.5-fold and endothelial cell seeding efficiency improved with treatment duration, with 60 min producing near-confluent monolayers. Mild alkaline heat treatment therefore improved immune compatibility and endothelialization while preserving mechanical integrity, offering a simple, scalable modification to advance plant-derived scaffolds for grafting. Full article

Coconut (Cocos nucifera L.) is one of the most widely cultivated crops, with increasing popularity and demand for its products, which necessitates increased production. However, the lack of high-quality planting materials is a major limitation in replanting the senile palms worldwide. This study examined the possibility of using a direct shoot organogenesis pathway as an alternative to somatic embryogenesis to produce clonal coconut plantlets using immature inflorescence explants obtained from Indonesia and Australia, through investigation of the explant types, exogenous plant growth regulators, and additives. Histological analysis showed suitable stages of immature inflorescence explants to be used, which led to the formation of shoot-like structures resembling true vegetative shoots, in all treatments consisting of exogenous plant growth regulators except for those without activated charcoal. The culture medium supplemented with thidiazuron (100 μM) alone or those supplemented with various combinations of other plant growth regulators showed similar shoot induction percentages (ca. 63 to 80%) or shoot-like structures per explant (ca. 6 to 8). The addition of adenine sulphate (217 μM) was found to significantly improve shoot induction (ca. 50%) from immature inflorescence explants compared to the control (ca. 5%), whereas phloroglucinol was found to negatively impact shoot induction, and L-glutamine showed a positive influence. The current study showed several improvements, which warrant further studies to develop commercial protocol for mass production of clonal coconut plantlets through direct organogenesis. Full article

Background: Dental implants are widely used to replace missing teeth, particularly in aesthetically sensitive areas. The implant’s macrogeometry is crucial for ensuring primary stability and successful osseointegration. Internal conical connections and reactive surfaces on implants have shown positive outcomes in tissue and bone stability. In response, a hybrid conical dental implant was designed to address a variety of clinical scenarios. Materials and Methods: This pilot study evaluated the performance of the hybrid conical implant using histological and micro-CT analysis in a preclinical model with immediate loading. Five implants were placed in a mongrel dog, and histomorphometric and micro-CT assessments were performed after 60 days of healing. Results: Analysis showed a high degree of osseointegration, with BIC at 61.56% and BT/TV at 77%. Micro-CT confirmed these findings, with nBIC at 82.20%. Vertical measurements indicated stable crestal bone. Peri-implant tissue displayed organized supracrestal connective tissue, without signs of inflammation or bone saucerization. Polarized light microscopy revealed collagen fibers in perpendicular and oblique orientations around the abutment, suggesting mechanical integration and biological sealing despite the absence of a prosthetic crown. Conclusions: Within the limitations of this exploratory study with one animal study, the hybrid conical implant showed favorable biological and structural responses under immediate loading. These preliminary findings provide useful insights for the refinement of implant design, although further investigations in larger preclinical and clinical studies are required before clinical applicability can be confirmed. Full article

Gliomas are aggressive brain tumours with diverse histological and molecular features, complicating accurate diagnosis and treatment. Dysregulated lipid metabolism contributes to glioma progression, and analysing lipid profiles in plasma and tissue may enhance diagnostic and prognostic accuracy. This study investigated lipid dysregulation to identify key lipid signatures that distinguish glioma from other brain diseases and examined the associations between lipid biomarkers in glioma tissue and plasma. Biospecimens from 11 controls and 72 glioma patients of varying grades underwent lipidomic profiling using liquid chromatography-mass spectrometry. Univariate and multivariate analyses identified differentially abundant lipids, and correlation analysis evaluated the associations between tissue and plasma biomarkers. Lipidomic analysis revealed distinct lipid profiles in the tissues and plasma of glioma patients compared to those of controls. Prominent lipid metabolites in glioma tissues included LPC 21:3 (AUC = 0.925), DG 43:11 (AUC = 0.906), and PC 33:1 (AUC = 0.892), which served as effective biomarkers. Conversely, in plasma, lipid metabolites such as phosphatidylethanolamine (PE 21:3, AUC = 0.862), ceramide-1-phosphate (CerP 26:1, AUC = 0.861), and sphingomyelin (SM 24:3, AUC = 0.858) were identified as the most promising lipid biomarkers. Significant positive and negative correlations were observed between the tissue and plasma lipid biomarkers of glioma patients. Lipidomic profiling revealed aberrant lipid classes and pathways in glioma tissues and plasma, enhancing understanding of glioma heterogeneity and potential clinical applications. Full article

Background and Objectives: Breast cancer (BC) is a complex disease requiring a comprehensive treatment approach due to its diverse characteristics. Critical molecular determinants of BC have been identified using advanced genomic, transcriptomic, and proteomic approaches. Assessing the biomarkers associated with the onset of early-stage BC may help identify the risk of metastasis and inform treatment decisions. A previous bioinformatic analysis using two large BC cohorts identified pumilio RNA binding family member 1 (PUM1) as a key gene in invasive BC. However, no study has yet examined the prognostic and predictive value of PUM1 in invasive BC and its correlation with aggressive tumor behavior. This study aimed to fill this need. Materials and Methods: Correlations between PUM1 expression and patients’ clinicopathological characteristics and outcomes were explored in publicly available BC transcriptomic data acquired using DNA microarrays (n = 10,872) and RNA sequencing (n = 4421) using BC Gene-Expression Miner v5.0. PUM1 expression in samples from 100 patients with invasive BC at King Abdul Aziz Specialist Hospital, Saudi Arabia, was assessed immunohistochemically. Correlations between PUM1 expression and patients’ clinicopathological characteristics (e.g., age, tumor grade, tumor size, and outcome) were assessed. The online platform ROC Plotter was also used to investigate the predictive significance of PUM1. Results: High PUM1 gene and protein expression correlated positively with aggressive features of BC, including high histological grade, high Ki-67 expression, negative hormone receptors, and the triple-negative BC molecular subtype. High PUM1 expression correlated with poor outcomes, and high PUM1 expression was associated with a lower pathological complete response to anti-endocrine treatment but a high response to chemotherapy. Conclusions: These results indicate that PUM1 may serve as a potential prognostic and predictive biomarker in patients with invasive BC. PUM1 may serve as a therapeutic target in BC cases with unfavorable prognoses. However, further validation in larger, multi-center cohorts and further functional assessment are required to deepen our understanding of PUM1’s role in BC. Full article

The adrenal glands are central to the stress response in cetaceans, yet their morphological and molecular changes under chronic stress remain poorly described. We investigated adrenal histology and protein composition in stranded common dolphins (Delphinus delphis) to assess whether post-mortem material can provide insights into stress physiology. Adrenal glands from 58 dolphins recovered along the Irish coast during a period of reported nutritional stress in the species were analyzed for adrenal mass, cortex-to-medulla (C:M) ratios, and cortical cell density. Additionally, two archival formalin-fixed, paraffin-embedded (FFPE) tissues were included in a pilot trial to assess the feasibility of protein extraction and mass spectrometry analysis. While adrenal mass did not differ significantly between stress types, chronically stressed dolphins exhibited significantly higher C:M ratios and cortical mass, consistent with cortical hypertrophy. Protein extraction from FFPE tissues was feasible, with the in-gel digestion method yielding more proteins (136) than the filter-aided sample preparation method (22). These findings demonstrate that histological and proteomic approaches can detect stress-related signatures in dolphins and highlight the potential of archival tissues for retrospective biomarker discovery. Full article