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Search Results (470)

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19 pages, 574 KB  
Review
Bridging Andrology and Oncology: Prognostic Indicators of Cancer Among Infertile Men
by Athanasios Zachariou, Efthalia Moustakli, Athanasios Zikopoulos, Maria Filiponi, Anastasios Potiris, Nikolaos Kathopoulis, Themos Grigoriadis, Maria Tzeli, Nikolaos Machairiotis, Ekaterini Domali, Nikolaos Thomakos and Sofoklis Stavros
Curr. Issues Mol. Biol. 2025, 47(11), 930; https://doi.org/10.3390/cimb47110930 - 8 Nov 2025
Viewed by 100
Abstract
Approximately 7% of males globally suffer from male infertility, which is becoming more widely acknowledged as a clinical indicator of potential health hazards as well as a cause of reproductive failure. Among these, cancer has become a significant worry due to mounting evidence [...] Read more.
Approximately 7% of males globally suffer from male infertility, which is becoming more widely acknowledged as a clinical indicator of potential health hazards as well as a cause of reproductive failure. Among these, cancer has become a significant worry due to mounting evidence that spermatogenesis impairment is associated with increased risk of prostate, testicular, and other cancers. Male infertility may be an early clinical manifestation of systemic genomic instability due to shared biological pathways, such as Y-chromosome microdeletions (AZF regions), germline DNA repair defects, mutations in tumor suppressor genes (e.g., BRCA1/2, TP53), mismatch repair gene mutations (e.g., MLH1, MSH2), and dysregulated epigenetic profiles. This narrative review covers the most recent research on prognostic markers of cancer in infertile men. These include molecular biomarkers such as genetic, epigenetic, and proteomic signatures; endocrine and hormonal profiles; and clinical predictors such as azoospermia, severe oligozoospermia, and a history of cryptorchidism. The possibility of incorporating these indicators into risk stratification models for precision medicine and early cancer surveillance is highlighted. For this high-risk group, bridging the domains of andrology and oncology may allow for better counseling, earlier detection, and focused therapies. Full article
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12 pages, 354 KB  
Article
Association Between MMR Status and Prognostic Pathological Factors in Endometrioid Endometrial Cancer—A Single-Center Retrospective Study
by Cezary Miedziarek, Hubert Bochyński, Katarzyna Bociańska, Michał Potograbski, Piotr Tyburski, Mikołaj Piotr Zaborowski and Ewa Nowak-Markwitz
Cancers 2025, 17(22), 3605; https://doi.org/10.3390/cancers17223605 - 8 Nov 2025
Viewed by 180
Abstract
Background/Objectives: Prognostic assessment in endometrial cancer (EC) is based on clinical and pathological features such as histological type, FIGO stage, tumor grade, LVSI, P53 status, and hormone receptor expression. Recent molecular research has distinguished four EC subtypes, with MMR status (pMMR vs. [...] Read more.
Background/Objectives: Prognostic assessment in endometrial cancer (EC) is based on clinical and pathological features such as histological type, FIGO stage, tumor grade, LVSI, P53 status, and hormone receptor expression. Recent molecular research has distinguished four EC subtypes, with MMR status (pMMR vs. dMMR) providing clinically relevant stratification due to its predictive value for immunotherapy. The present study aims to compare dMMR and pMMR tumors in terms of the prevalence of adverse histopathological prognostic factors. Methods: This retrospective study included 179 patients with endometrioid endometrial carcinoma (EEC) treated at the authors’ institution (1 January 2023–31 August 2025). Patients were classified by MMR status (pMMR vs. dMMR) based on immunohistochemistry, and clinicopathological variables, including FIGO stage, myometrial invasion depth, tumor grade, LVSI, ER/PR expression, and P53 status, were analyzed. Normality was assessed using the Shapiro–Wilk test. Categorical variables were tested with chi-square or Fisher’s exact tests, reporting odds ratios with 95% CI, while continuous variables were compared using the Mann–Whitney test and presented as median (IQR) with the Hodges–Lehmann difference and 95% CI. Multivariable logistic regression with Wald tests was performed. Results: dMMR tumors accounted for 29.05% of all cases. Patients in the dMMR group were significantly more likely to present with FIGO stage III/IV disease (p = 0.036) and to exhibit LVSI (p = 0.008). No differences were observed between the groups with respect to tumor grade, estrogen receptor positivity, progesterone receptor positivity, or the prevalence of deep myometrial invasion. The most frequent pattern of protein loss in the dMMR population was concurrent loss of MLH1 and PMS2. Conclusions: In the studied population, dMMR tumors more frequently exhibited adverse prognostic features of EC, such as advanced stage of disease and lymphovascular space invasion. This suggests the potential for effective immunotherapy in this patient group. Full article
(This article belongs to the Section Cancer Pathophysiology)
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20 pages, 5977 KB  
Article
Assessment of Continuous Flow-Dependent Red Cell Aggregation Using a Microfluidic Chip
by Yang Jun Kang
Appl. Sci. 2025, 15(21), 11481; https://doi.org/10.3390/app152111481 - 27 Oct 2025
Viewed by 267
Abstract
Measuring RBC aggregation can be considered as a valuable tool for detecting pathological diseases. Most previous methods need to stop and run blood flows periodically. Thus, it is impossible to probe RBC aggregation in continuously varying infusion flow. To resolve the issues, a [...] Read more.
Measuring RBC aggregation can be considered as a valuable tool for detecting pathological diseases. Most previous methods need to stop and run blood flows periodically. Thus, it is impossible to probe RBC aggregation in continuously varying infusion flow. To resolve the issues, a novel bifurcated continuous-flow mechanism is suggested to probe RBC aggregation without periodic interruption of blood flow. A microfluidic chip is then designed to split single flow into two branches (low flow rate and high flow rate). RBC aggregation occurs in the low flow-rate channel, whereas it is dispersed fully in the high flow-rate channel. Using a syringe pump, blood is infused into a microfluidic chip at constant and sinusoidal pattern. RBC aggregation index (AI) is calculated from time-lapse imaging intensity within each channel. From fluidic circuit analysis and experimental results, the optimal infusion flow rate is determined as Qsp = 0.5~2 mL/h. The AI is higher at Hct = 30% than at Hct = 50%. The high concentration of dextran solution increases AI considerably. The period of pulsatile infusion flow rate has a strong influence on time-lapse AI. In conclusion, the present method can be capable of measuring time-lapse AI consistently, without interrupting infusion flow. Full article
(This article belongs to the Special Issue Current Applications of Microfluidics for Biosensing and Diagnostics)
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22 pages, 18413 KB  
Article
The Effect of Bilayered Bioactive Coating on Polycaprolactone Electrospun Scaffold Biocompatibility, Bioabsorption and Cellular Properties
by Victor I. Sevastianov, Evgeniy A. Nemets, Alexey M. Grigoriev, Aleksandra D. Belova, Vyacheslav Yu. Belov, Lyudmila A. Kirsanova, Anna S. Ponomareva, Nikita V. Grudinin, Vladimir K. Bogdanov, Alla O. Nikolskaya, Eugenia G. Kuznetsova, Ekaterina A. Guseva, Yulia B. Basok and Sergey V. Gautier
Polymers 2025, 17(21), 2813; https://doi.org/10.3390/polym17212813 - 22 Oct 2025
Viewed by 365
Abstract
Bioabsorbable scaffolds from synthetic polyesters are widely used in the field of tissue engineering. However, their hydrophobic surface and lack of suitable functional groups are the main limitations related to cell attachment. The aim of this research was to modify the surface of [...] Read more.
Bioabsorbable scaffolds from synthetic polyesters are widely used in the field of tissue engineering. However, their hydrophobic surface and lack of suitable functional groups are the main limitations related to cell attachment. The aim of this research was to modify the surface of polycaprolactone (PCL) scaffolds using a bioactive coating containing heparin bound via albumin spacer and platelet lysate over heparin. Porous scaffolds were produced by electrospinning from 10% PCL (w/w) solution in methylene chloride (25 kV voltage, 100 mm distance between electrodes and 4 mL/h feedrate), which demonstrated 5.5 ± 1.1 MPa Young’s modulus, 2.5 ± 0.4 MPa tensile strength and 321 ± 29% elongation at break. Bioactive coating does not change the structure and mechanical properties of the scaffolds. Treated scaffolds are biocompatible and have no cytotoxic effect in direct contact with cells. Functionalization also promotes the in vitro adhesion and proliferation of human adipose mesenchymal stromal cells. After 7 days of incubation, the PCL scaffold modified with the heparin–platelet lysate complex had a cell density of 185.6 ± 15.7 cells/mm2 compared to 79.5 ± 7.8 cells/mm2 for nontreated control. The intramuscular implantation of scaffolds revealed that immobilization of heparin alone prolongs the acute phase of the inflammatory reaction. However, subsequent treatment with platelet lysate minimizes the inflammatory reaction, slows the rate of implant absorption, and accelerates vascularization. The results obtained show that the developed bioactive coating improves the cellular properties of PCL electrospun scaffolds and can be used to form in vivo tissue-engineered constructs. Full article
(This article belongs to the Special Issue Polymer Innovations in Biomedicine)
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17 pages, 2819 KB  
Article
Effect of Hydroxyvalerate Molar Percentage on Physicochemical and Degradation Properties of Electrospun Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) Fibrous Membranes and Potential Application for Air Filtration
by Yaohui Liu, Cheng-Hao Lee, Yanming Wang, Chi-Wai Kan and Xiao-Ying Lu
Polymers 2025, 17(20), 2719; https://doi.org/10.3390/polym17202719 - 10 Oct 2025
Viewed by 477
Abstract
This study investigates the air filtration capabilities of fibrous membranes fabricated via electrospinning, with a focus on optimizing processing parameters. Specifically, Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), a well-characterized biodegradable polyester, was electrospun to produce membranes exhibiting precisely controlled surface microstructures. The optimal fiber morphology was attained [...] Read more.
This study investigates the air filtration capabilities of fibrous membranes fabricated via electrospinning, with a focus on optimizing processing parameters. Specifically, Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), a well-characterized biodegradable polyester, was electrospun to produce membranes exhibiting precisely controlled surface microstructures. The optimal fiber morphology was attained under conditions of a 20 kV applied electric field, a solution flow rate of 0.5 mL·h−1, a polymer concentration of 13 wt.%, and a needle inner diameter of 0.21 mm. The microstructural features of the electrospun PHBV membranes were characterized using scanning electron microscopy (SEM). Complementary analysis via 13C nuclear magnetic resonance (NMR) spectroscopy confirmed that the membranes comprised pure 3-hydroxyvalerate (3HV) copolymerized with 3-hydroxybutyrate (3HB) terminal units, with 3HV mole fractions ranging from 17% to 50%. The incorporation of different molar percentages of 3HV in PHBV membrane significantly enhances its durability, as evidenced by Ball Burst Strength (BBS) measurements, with an elongation at burst that is 65–86% greater than that of ASTM F2100 level 3 mask. The nanofibrous membranes exhibited a controlled pore size distribution, indicating their potential suitability for air filtration applications. Particle filtration efficiency (PFE) assessments under standard atmospheric pressure conditions showed that the optimized electrospun PHBV membranes achieved filtration efficiencies exceeding 98%. Additionally, the influence of 3HV content on biodegradation behavior was evaluated through soil burial tests conducted over 90 days. Results indicated that membranes with lower 3HV content (17 mol.%) experienced the greatest weight loss, suggesting accelerated degradation in natural soil environments. Full article
(This article belongs to the Section Polymer Membranes and Films)
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24 pages, 5442 KB  
Article
Electro-Spun Waste Polystyrene/Steel Slag Composite Membrane for Water Desalination: Modelling and Photothermal Activity Evaluation
by Salma Tarek Ghaly, Usama Nour Eldemerdash and Ahmed H. El-Shazly
Membranes 2025, 15(10), 294; https://doi.org/10.3390/membranes15100294 - 28 Sep 2025
Viewed by 1377
Abstract
Plastic waste and industrial residues like steel slag pose significant environmental challenges, with limited recycling solutions. This study investigates a sustainable approach by repurposing waste polystyrene and steel slag into composite membranes via electrospinning for membrane distillation applications. Steel slag incorporation enhanced membrane [...] Read more.
Plastic waste and industrial residues like steel slag pose significant environmental challenges, with limited recycling solutions. This study investigates a sustainable approach by repurposing waste polystyrene and steel slag into composite membranes via electrospinning for membrane distillation applications. Steel slag incorporation enhanced membrane porosity, hydrophobicity, and thermal stability, with process optimization performed through response surface methodology by varying slag content (0–10 wt%), voltage (15–30 kV), and feed rate (0.18–10 mL·h−1). Optimized membranes achieved a reduced fiber diameter (1.172 µm), high porosity (82.3%), and superior hydrophobicity (contact angle 102.2°). Mechanical performance improved with a 12% increase in tensile strength and a threefold rise in liquid entry pressure over pure polystyrene membranes, indicating greater durability and wetting resistance. In direct contact membrane distillation, water flux improved by 15% while maintaining salt rejection above 98%. Under photothermal membrane distillation, evaporation rates rose by 69% and solar-to-thermal conversion efficiency by 60% compared to standard PVDF membranes. These results demonstrate the feasibility of transforming waste materials into high-performance, durable membranes, offering a scalable and eco-friendly solution for sustainable desalination. Full article
(This article belongs to the Section Membrane Applications for Water Treatment)
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28 pages, 1312 KB  
Review
Traditional and New Views on MSI-H/dMMR Endometrial Cancer
by Chuqi Liu, Huiyu Ping, Mengmeng Yao, Xinru Li, Qingxin Li, Ruotong Hu, Yawen Xu, Kaidi Meng, Fei Gao and Kai Meng
Biomolecules 2025, 15(10), 1370; https://doi.org/10.3390/biom15101370 - 26 Sep 2025
Viewed by 1133
Abstract
MSI-H/dMMR endometrial cancer (EC) is closely linked to the mismatch repair (MMR) pathway, and its pathogenesis is associated with microsatellite instability (MSI) caused by abnormalities in the core genes of the conventional MMR system. This cancer exhibits a distinct immune microenvironment, which makes [...] Read more.
MSI-H/dMMR endometrial cancer (EC) is closely linked to the mismatch repair (MMR) pathway, and its pathogenesis is associated with microsatellite instability (MSI) caused by abnormalities in the core genes of the conventional MMR system. This cancer exhibits a distinct immune microenvironment, which makes it suitable for treatment with immune checkpoint inhibitors (ICIs). This cancer type demonstrates heterogeneity, encompassing Lynch syndrome (LS)-associated EC (characterized by germline mutations), sporadic EC (attributed to MLH1 promoter hypermethylation), and Lynch-like EC (driven by somatic mutations). Research indicates that these three dMMR EC subtypes possess different immune microenvironments, which may influence the therapeutic efficacy of ICIs. However, the impact of somatic mutations in traditional MMR genes on EC has often been overlooked. Furthermore, over 50% of patients with MSI exhibit no response to ICIs, potentially due to abnormalities in nontraditional MMR genes. This review discusses the role of traditional and nontraditional MMR genes in dMMR EC and related treatment strategies, highlights key issues in the current diagnosis and treatment of dMMR EC, and aims to enhance understanding of its heterogeneity and advance precision diagnosis and treatment. Full article
(This article belongs to the Special Issue Human Reproductive Biology: Uncertainties and Controversies)
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22 pages, 3810 KB  
Article
Nanofibrous Polymer Filters for Removal of Metal Oxide Nanoparticles from Industrial Processes
by Andrzej Krupa, Arkadiusz Tomasz Sobczyk and Anatol Jaworek
Membranes 2025, 15(10), 291; https://doi.org/10.3390/membranes15100291 - 25 Sep 2025
Viewed by 787
Abstract
Filtration of submicron particles and nanoparticles is an important problem in nano-industry and in air conditioning and ventilation systems. The presence of submicron particles comprising fungal spores, bacteria, viruses, microplastic, and tobacco-smoke tar in ambient air is a severe problem in air conditioning [...] Read more.
Filtration of submicron particles and nanoparticles is an important problem in nano-industry and in air conditioning and ventilation systems. The presence of submicron particles comprising fungal spores, bacteria, viruses, microplastic, and tobacco-smoke tar in ambient air is a severe problem in air conditioning systems. Many nanotechnology material processes used for catalyst, solar cells, gas sensors, energy storage devices, anti-corrosion and hydrophobic surface coating, optical glasses, ceramics, nanocomposite membranes, textiles, and cosmetics production also generate various types of nanoparticles, which can retain in a conveying gas released into the atmosphere. Particles in this size range are particularly difficult to remove from the air by conventional methods, e.g., electrostatic precipitators, conventional filters, or cyclones. For these reasons, nanofibrous filters produced by electrospinning were developed to remove fine particles from the post-processing gases. The physical basis of electrospinning used for nanofilters production is an employment of electrical forces to create a tangential stress on the surface of a viscous liquid jet, usually a polymer solution, flowing out from a capillary nozzle. The paper presents results for investigation of the filtration process of metal oxide nanoparticles: TiO2, MgO, and Al2O3 by electrospun nanofibrous filter. The filter was produced from polyvinylidene fluoride (PVDF). The concentration of polymer dissolved in dimethylacetamide (DMAC) and acetone mixture was 15 wt.%. The flow rate of polymer solution was 1 mL/h. The nanoparticle aerosol was produced by the atomization of a suspension of these nanoparticles in a solvent (methanol) using an aerosol generator. The experimental results presented in this paper show that nanofilters made of PVDF with surface density of 13 g/m2 have a high filtration efficiency for nano- and microparticles, larger than 90%. The gas flow rate through the channel was set to 960 and 670 l/min. The novelty of this paper was the investigation of air filtration from various types of nanoparticles produced by different nanotechnology processes by nanofibrous filters and studies of the morphology of nanoparticle deposited onto the nanofibers. Full article
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20 pages, 1388 KB  
Review
Mismatch Repair Deficiency and the Role of Non-Canonical Functions in Cancer: Diagnosis and Therapeutic Implications
by Alicja Dąbrowska, Jakub Mastalerz, Zofia Łapińska, Iwona Deszcz, Agnieszka Chwiłkowska and Nina Rembiałkowska
Int. J. Mol. Sci. 2025, 26(19), 9312; https://doi.org/10.3390/ijms26199312 - 24 Sep 2025
Viewed by 759
Abstract
The mismatch repair system is critical for correcting base–base mismatches and insertion-deletion loops during DNA replication. Deficiencies in MMR (due to mutations in MLH1, MSH2, MSH6, or PMS2) lead to microsatellite instability and contribute to the development of various cancers, such as Lynch [...] Read more.
The mismatch repair system is critical for correcting base–base mismatches and insertion-deletion loops during DNA replication. Deficiencies in MMR (due to mutations in MLH1, MSH2, MSH6, or PMS2) lead to microsatellite instability and contribute to the development of various cancers, such as Lynch syndrome-related colorectal cancer and sporadic tumors. This review will delve into the molecular basis of MMR deficiency. Additionally, the review will cover diagnostic approaches for detecting MSI and MMR deficiency, including next-generation sequencing and PCR-based methods. The implications for treatment will be discussed, emphasizing immune checkpoint inhibitors (e.g., pembrolizumab) that target tumors with high mutational burdens due to MMR deficiency, as well as novel therapeutic approaches like synthetic lethality exploiting DNA repair vulnerabilities. Full article
(This article belongs to the Special Issue Targeted Therapies and Molecular Methods in Cancer, 3rd Edition)
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19 pages, 3467 KB  
Article
Lubrication Mechanism and Establishment of a Three-Phase Lubrication Model for SCCO2-MQL Ultrasonic Vibration Milling of SiCp/Al Composites
by Bowen Wang and Huiping Zhang
Machines 2025, 13(9), 879; https://doi.org/10.3390/machines13090879 - 22 Sep 2025
Viewed by 523
Abstract
SiCp/Al composites (Silicon Carbide Particle-Reinforced Aluminum Matrix Composites), due to their light weight, high strength, and superior wear resistance, are extensively utilized in aerospace and other sectors; nonetheless, they are susceptible to tool wear and surface imperfections during machining, which negatively impact overall [...] Read more.
SiCp/Al composites (Silicon Carbide Particle-Reinforced Aluminum Matrix Composites), due to their light weight, high strength, and superior wear resistance, are extensively utilized in aerospace and other sectors; nonetheless, they are susceptible to tool wear and surface imperfections during machining, which negatively impact overall machining performance. Supercritical carbon dioxide minimal quantity lubrication (SCCO2-MQL) is an environmentally friendly and efficient lubrication method that significantly improves interfacial lubricity and thermal stability. Nonetheless, current lubrication models are predominantly constrained to gas–liquid two-phase scenarios, hindering the characterization of the three-phase lubrication mechanism influenced by the combined impacts of SCCO2 phase transition and ultrasonic vibration. This study formulates a lubricant film thickness model that incorporates droplet atomization, capillary permeation, shear spreading, and three-phase modulation while introducing a pseudophase enhancement factor βps(p,T) to characterize the phase fluctuation effect of CO2 in the critical region. Simulation analysis indicates that, with an ultrasonic vibration factor Af = 1200 μm·kHz, a lubricant flow rate Qf = 16 mL/h, and a pressure gradient Δptot = 6.0 × 105 Pa/m, the lubricant film thickness attains its optimal value, with Δptot having the most pronounced effect on the film thickness (normalized sensitivity S = 0.488). The model results align with the experimental trends, validating its accuracy and further elucidating the nonlinear regulation of the film-forming process by various parameters within the three-phase synergistic lubrication mechanism. This research offers theoretical backing for the enhancement of performance and the expansion of modeling in SCCO2-MQL lubrication systems. Full article
(This article belongs to the Special Issue Machine Tools for Precision Machining: Design, Control and Prospects)
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15 pages, 2505 KB  
Article
Perfusion Enhancement via Continuous Brachial Plexus Block to Prevent Vascular Insufficiency in Replanted Digits: A Prospective, Randomized Controlled Trial
by Yang Xu, Fang Xie, Yan Wang, Jie Chen, Shenghe Liu and Tao Xu
J. Clin. Med. 2025, 14(18), 6591; https://doi.org/10.3390/jcm14186591 - 18 Sep 2025
Viewed by 436
Abstract
Background/Objectives: Pain-induced vasoconstriction and thrombosis cause vascular insufficiency, a major etiology of early necrosis in replanted digits. While systemic intravenous analgesia (SIVA) carries significant side effects, continuous brachial plexus block (CBPB) provides analgesia with vasodilation. Amidst uncertainties regarding distal vascular recanalization and sympathetic [...] Read more.
Background/Objectives: Pain-induced vasoconstriction and thrombosis cause vascular insufficiency, a major etiology of early necrosis in replanted digits. While systemic intravenous analgesia (SIVA) carries significant side effects, continuous brachial plexus block (CBPB) provides analgesia with vasodilation. Amidst uncertainties regarding distal vascular recanalization and sympathetic denervation, whether CBPB’s hemodynamic effects translate into improved perfusion and outcomes in replanted digits remains unknown. This randomized controlled trial compared the effects of CBPB versus SIVA on digit perfusion, vascular insufficiency, and survival rates post-replantation. Methods: After screening 113 patients, 55 patients (71 digits) were ultimately randomized and analyzed: the CBPB group (n = 27, 36 digits) received 0.2% ropivacaine infusion at 5 mL/h; the SIVA group (n = 28, 35 digits) received intravenous parecoxib 20 mg twice daily with supplemental tramadol for visual analog scale (VAS) scores > 3. The primary outcome was digital skin temperature trajectory measured at 0, 12, 24, 36, and 48 h postoperatively. Secondary outcomes included Doppler-quantified combined volumetric flow rate of the radial and ulnar arteries (RA-UA VFR) at identical timepoints, VAS scores, vascular insufficiency incidence, and 7-day digit survival. Results: CBPB significantly enhanced perfusion in replanted digits at all postoperative timepoints, with digital skin temperature peaking at 48 h (32 ± 1.6 °C vs. 31 ± 1.1 °C; p < 0.001) and RA-UA VFR peaking at 24 h (4.0 ± 0.83 vs. 1.8 ± 0.51 mL/s; p < 0.001) versus SIVA. Concurrently, CBPB provided superior analgesia (VAS 0.52 ± 0.51 vs. 1.9 ± 1.0; p < 0.001) and significantly reduced 48-h vascular insufficiency incidence (8.3% vs. 29%; p = 0.028). No significant difference was observed in seven-day survival rates between groups (97% vs. 91%; p = 0.329). Conclusions: CBPB significantly enhanced perfusion in replanted digits and reduced the incidence of vascular insufficiency, despite not conferring additional survival benefits. Full article
(This article belongs to the Section Anesthesiology)
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14 pages, 485 KB  
Article
Microsatellite Instability and Myometrial Infiltration in Low-Grade Endometrial Cancer: A Focus on MMR Heterodimer Dysfunction by a Retrospective Multicentric Italian Study
by Carlo Ronsini, Stefano Restaino, Mariano Catello Di Donna, Giuseppe Cucinella, Maria Cristina Solazzo, Pasquale De Franciscis, Giuseppe Vizzielli, Manuela Ludovisi and Vito Chiantera
J. Pers. Med. 2025, 15(9), 417; https://doi.org/10.3390/jpm15090417 - 2 Sep 2025
Viewed by 1220
Abstract
Background: Recent studies highlight the role of microsatellite instability (MSI) in tumor progression. This study examines the link between MSI, type of loss of function, and disease progression in low-grade endometrial carcinoma clinically confined to the uterus, focusing on myometrial infiltration. Materials and [...] Read more.
Background: Recent studies highlight the role of microsatellite instability (MSI) in tumor progression. This study examines the link between MSI, type of loss of function, and disease progression in low-grade endometrial carcinoma clinically confined to the uterus, focusing on myometrial infiltration. Materials and Methods: This retrospective case-control study analyzed data from 144 women treated for clinical stage I low-grade endometrial carcinoma at two university hospitals. Patients were divided into two groups based on microsatellite status: 118 with microsatellite stability (MSS) and 26 with MSI. Immunohistochemical profiling assessed MMR proteins (MLH1, PMS2, MSH2, MSH6). The primary outcome was the presence of myometrial infiltration, and the secondary outcome was the deepness of infiltration. Data were statistically analyzed using Fisher’s exact, Chi-square, and Wilcoxon tests, with logistic regression applied to evaluate the impact of MSI on these outcomes. Results: Myometrial infiltration was present in 96% of MSS and 98% of MSI cases (p = 0.5). However, deep infiltration (≥50%) was more frequent in patients with MSI (38% vs. 19%, p = 0.042). Stratification by heterodimer loss revealed that loss of MLH1/PMS2 was associated with a higher rate of deep infiltration (47%), while loss of MSH2/MSH6 correlated with lower infiltration risk (14%). In multivariate analysis, MSH2/MSH6 loss remained negatively associated with infiltration (OR 0.88; 95% CI 0.80–0.98; p = 0.020), independent of grade and LVSI. Conclusions: In low-grade endometrial carcinomas clinically confined to the uterus, MSI does not increase the overall prevalence of myometrial infiltration but is associated with deeper invasion, especially in cases with MLH1/PMS2 loss. MSI profiling could aid in risk stratification and therapeutic planning, particularly in candidates for fertility-sparing treatment. Full article
(This article belongs to the Special Issue Gynecological Oncology: Personalized Diagnosis and Therapy)
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16 pages, 1128 KB  
Article
CK2α Overexpression in Colorectal Cancer: Evidence for Sex- and Age-Linked Differences
by Jana Romy Friedrich, Clara Meier, Guido Plotz, Stefan Zeuzem, Angela Brieger and Sarah J. Overby
Cancers 2025, 17(17), 2857; https://doi.org/10.3390/cancers17172857 - 30 Aug 2025
Viewed by 1067
Abstract
Background/Objectives: Colorectal cancer (CRC) remains a leading cause of cancer-related deaths, with notable sex-specific differences in its incidence, diagnosis, and outcomes. Our previous work identified casein kinase 2 alpha (CK2α) as being capable of impairing DNA mismatch repair (MMR) via phosphorylation of MLH1, [...] Read more.
Background/Objectives: Colorectal cancer (CRC) remains a leading cause of cancer-related deaths, with notable sex-specific differences in its incidence, diagnosis, and outcomes. Our previous work identified casein kinase 2 alpha (CK2α) as being capable of impairing DNA mismatch repair (MMR) via phosphorylation of MLH1, thereby increasing the tumor mutational burden. This study aimed to investigate sex-specific differences in CK2α protein expression in CRC. Methods: Immunohistochemical (IHC) analysis was performed on 161 CRC tumors and adjacent normal tissues to quantify the CK2α protein levels. A multi-cohort meta-analysis of proteomic and clinical data was conducted to validate our findings and assess the correlations with age, sex, and relevant signaling pathways. Results: Female CRC patients exhibited significantly higher CK2α expression than male patients, which was confirmed in two independent cohorts. Additionally, CK2α expression was positively correlated with age in female but not male patients. Cross-cohort correlation analyses linked CK2α levels with key proteins involved in estrogen receptor signaling and aging, including DEAD-box helicase 5 (DDX5), histone deacetylase 1 (HDAC1), proliferating cell nuclear antigen (PCNA), prohibitin-2 (PHB2), H/ACA ribonucleoprotein complex subunit 2 (NHP2), and dual-specificity mitogen-activated protein kinase kinase 3 (MAP2K3). Conclusions: CK2α is significantly overexpressed in the tumor tissue of female CRC patients and shows a strong age-related correlation. These findings suggest a sex- and age-specific regulatory mechanism potentially influenced by estrogen signaling or menopause. Such dimorphisms underscore the need for sex-specific strategies in CRC biomarker development and therapy. Full article
(This article belongs to the Section Cancer Immunology and Immunotherapy)
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15 pages, 974 KB  
Article
Genetic Variants Associated with Breast Cancer Are Detected by Whole-Exome Sequencing in Vietnamese Patients
by Nguyen Van Tung, Nguyen Thi Kim Lien, Le Duc Huan, Pham Cam Phuong, Bui Bich Mai, Nguyen Thi Hoa Mai, Tran Thi Thanh Huong, Phung Thi Huyen, Nguyen Van Chu, Tran Van Dung, Luu Hong Huy, Dong Chi Kien, Dang Van Manh, Duong Minh Long, Nguyen Ngoc Lan, Nguyen Thanh Hien, Ha Hong Hanh and Nguyen Huy Hoang
Diagnostics 2025, 15(17), 2187; https://doi.org/10.3390/diagnostics15172187 - 28 Aug 2025
Viewed by 1024
Abstract
Background: Breast cancer (BC) is the most common cancer and the leading cause of cancer death in women. Hereditary BC risk accounts for 25% of all cases. Pathological variants in known BC precursor genes explain only about 30% of hereditary BC cases, while [...] Read more.
Background: Breast cancer (BC) is the most common cancer and the leading cause of cancer death in women. Hereditary BC risk accounts for 25% of all cases. Pathological variants in known BC precursor genes explain only about 30% of hereditary BC cases, while the underlying genetic factors in most families remain unknown. Identifying hereditary cancer risk factors will help improve genetic counseling, cancer prevention, and cancer care. Methods: Here, we used whole-exome sequencing (WES) to identify genetic variants in 105 Vietnamese patients with BC and 50 healthy women. BC-associated variants were screened by the Franklin software and the criteria of the American College of Medical Genetics and Genomics (ACMG) and evaluated based on in silico analysis. Results: In total, 56 variants were identified in 37 genes associated with BC, including ACVR1B, APC, AR, ARFGEF1, ATM, ATR, BARD1, BLM, BRCA1, BRCA2, CASP8, CASR, CHD8, CTNNB1, ESR1, FAN1, FGFR2, HMMR, KLLN, LZTR1, MCPH1, MLH1, MSH2, MSH3, MSH6, NF1, PMS2, PRKN, RAD54L, RB1CC1, RECQL, SLC22A18, SLX4, SPTBN1, TP53, WRN, and XRCC3 in 41 patients. Among them, 12 variants were novel, and 10 variants were assessed as pathogenic/likely pathogenic by ACMG and ClinVar. Variants of uncertain significance (VUS) were evaluated using in silico prediction software to predict whether they are likely to cause the disease in patients. Conclusions: This is the first WES study to identify BC-associated genetic variants in Vietnamese patients, providing a comprehensive database of BC susceptibility gene variants. We suggest using WES as a tool to identify genetic variants in BC patients for risk prediction and treatment guidance. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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Article
Perioperative Myocardial Injury and Acute Kidney Injury in Patients Undergoing Hepatic Resection: Incidence, Risk Factors, and Effects on Outcomes
by Taner Abdullah, Mert Şentürk, Hürü Ceren Gökduman, İşbara Alp Enişte, İlyas Kudaş, Özgür Bostancı, Erdem Kınacı, İlgin Özden and Funda Gümüş Özcan
J. Clin. Med. 2025, 14(17), 6080; https://doi.org/10.3390/jcm14176080 - 28 Aug 2025
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Abstract
Background/Objectives: Perioperative organ injury (POI) is frequently observed following hepatectomy as acute kidney injury (AKI), perioperative myocardial injury (PMI), or both. We aimed to determine the incidences of POI, PMI, and AKI, reveal the risk factors and predictive tools for POI occurrence, and [...] Read more.
Background/Objectives: Perioperative organ injury (POI) is frequently observed following hepatectomy as acute kidney injury (AKI), perioperative myocardial injury (PMI), or both. We aimed to determine the incidences of POI, PMI, and AKI, reveal the risk factors and predictive tools for POI occurrence, and evaluate the relationship between POI and patient outcomes. Methods: This was a single-center historical cohort study of consecutive patients. The primary endpoint was the occurrence of POI within 3 days following hepatectomy. Results: Out of 128 patients, POI, PMI, and AKI occurred in 48 (37.5%), 36 (28.1%), and 23 (18%) patients, respectively. Ten (7.8%) patients suffered from both PMI and AKI. The presence of chronic kidney disease or systolic/valvular heart disease, fluid balance more than 365 mL/h, and intraoperative bleeding more than 950 mL were the risk factors for POI. A tool created by using the intraoperative decline of central venous oxygen saturation and lactate value during skin closure performed well in predicting POI (area under the ROC curve: 0.79, p < 0.001). In patients with POI, the number of those who needed intensive care unit (ICU) follow-up for more than 1 day was significantly higher (21% vs. 6%, p: 0.01). The length of hospital stay for these patients was significantly longer as well (11 (8–18) vs. 9 (7–13) days, p: 0.02). Two patients (20% of 10 patients who suffered from both AKI and PMI) died in the 90-day follow-up. Conclusions: POI is a common complication following hepatectomy and is associated with longer hospital and ICU stays. Patients who suffer from both AKI and PMI have a higher risk of mortality. Full article
(This article belongs to the Section Anesthesiology)
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