Search Results (51)

Background: High-grade serous ovarian carcinoma (HGSOC) can be subdivided into four prognostic molecular subtypes based on gene expression: C1/Mesenchymal (C1.MES), C2/Immunoreactive (C2.IMM), C4/Differentiated (C4.DIF) and C5/Proliferative (C5.PRO), each representing distinct biological characteristics with immune and stromal microenvironments. PrOTYPE enables prognosis and treatment guidance from biopsy material. Metastatic biopsies are often more accessible than primary adnexal sampling; their utility assumes stable tumor-intrinsic properties relative to the primary. Metastases may diverge due to microenvironmental pressure as well as the site-specific subtype dynamics. Methods: Treatment-naïve HGSOC specimens from 138 patients were profiled using the 55-gene nanostring PrOTYPE assay at adnexal, contralateral adnexal, and/or metastatic sites. Results: Adnexal PrOTYPE yielded expected distributions (21% C1.MES, 31% C2.IMM, 23% C4.DIF, 25% C5.PRO) with moderate reproducibility (κ = 0.49). Same-site replicate analysis showed substantial reproducibility (κ = 0.7). Non-adnexal sites were enriched for immune/mesenchymal subtypes (C1.MES/C2.IMM, 36/63 cases), most prominently at the omentum (24/32 C1.MES). C5.PRO was distinctly underrepresented at non-adnexal sites. Subtype shifts from adnexal to extra-adnexal sites were enriched for the second-place adnexal type prediction (p < 0.001). Detailed 55-gene analysis showed POSTN/CTSK were most commonly upregulated across metastatic sites. EMT pathway enrichment increased with metastatic distance (from adnexa to omentum, adj p < 0.05), paralleling—but independent of—C1.MES predominance. Conclusions: Adnexal PrOTYPE showed good stability. However, non-random subtype shifts and EMT enrichment at metastatic sites suggest dissemination selects pre-existing transcriptional plasticity rather than acquiring states de novo as HGSOC adapts to new microenvironments. Microenvironment changes may help predict metastatic potential and should be considered for precision medicine targeting. Full article

Cell migration is a fundamental process in cancer progression, playing a central role in tumor invasion and metastasis. This highly coordinated behavior is regulated by dynamic interactions between cancer cells and extracellular environment. Among the different tumor types, glioblastoma (GB) represents a particularly aggressive form of cancer in which enhanced migratory capacity is a key determinant of diffuse brain infiltration, tumor recurrence, and poor prognosis. In this context, extracellular vesicles (EVs) have emerged as important mediators, regulating cell migration in several cancer types, including GB. EVs are lipid bilayer-enclosed nano- and micro-sized particles, containing various bioactive molecules that can target specific recipient cells, thereby modulating cellular properties, including the migratory behavior. Among the available methods for studying cell migration, the wound healing assay is the most widely used. Although simple, cost-effective and not requiring sophisticated equipment, its reliability and reproducibility can be affected by technical variability and the diversity of existing protocols. Here, we present an optimized protocol for executing and analyzing a cellular wound healing assay designed to assess EV-mediated migration in GB cells. The protocol incorporates the use of silicone culture inserts to enhance wound homogeneity and reproducibility, together with continuous Mitomycin C incubation to inhibit cell proliferation without inducing cytotoxicity, enabling specific assessment of cell migration. We outline a step-by-step description of the procedure, detailing all required materials and equipment and highlighting critical steps, checkpoints, and key parameters. This method provides a robust framework for reproducible wound healing assays to investigate EV effects on GB cell migration. Full article

Background and Objectives: Neuroblastoma represents the most common extracranial solid tumor in childhood and is associated with a poor prognosis in high-risk cases. Amygdalin, a naturally occurring cyanogenic glycoside, has been reported to exhibit anti-tumor properties in various cancer models; however, its effects on neuroblastoma cells remain insufficiently characterized. The present study was conducted with the objective of investigating the effects of amygdalin on cell proliferation, apoptosis, and invasion in SH-SY5Y neuroblastoma cells in vitro. Materials and Methods: The SH-SY5Y neuroblastoma cells were cultivated under the optimal conditions for their growth. The cytotoxic effect of amygdalin was determined using the CCK8 assay, which is dose- and time-dependent. Total RNA isolation was performed using Trizol. Subsequently, a process of cDNA synthesis was initiated. The real-time PCR method was utilized to ascertain alterations in the expression levels of mRNA molecules associated with apoptosis, namely Bax, Bcl2, caspase-3, caspase-7, caspase-8, caspase-9, caspase-10, NFkB, and invasion-related genes MMP2, MMP9, TIMP1, and TIMP3. Furthermore, alterations in NFkB levels were examined through the utilization of the ELISA method. Results: The IC50 value of amygdalin in SH-SY5Y cells was determined to be 112.7 µM at 24 h. Amygdalin demonstrated a dose-dependent cytotoxic effect on neuroblastoma cells. Furthermore, the study revealed that the drug induced apoptosis through the upregulation of BAX and BID, and the downregulation of BCL-2 and NF-κB. This process led to a reduction in cell proliferation. Furthermore, the study demonstrated an anti-invasive effect through the downregulation of MMP9 and the upregulation of TIMP1 and TIMP3. In addition, a substantial decrease in NF-κB protein concentration was observed. Conclusions: These findings demonstrate that amygdalin exerts anti-proliferative, pro-apoptotic, and anti-invasive effects in SH-SY5Y neuroblastoma cells in vitro. Amygdalin may represent a promising natural compound for further investigation as a potential therapeutic agent in neuroblastoma. Full article

The proper selection of bioactive root-end material is one of the main prognostic factors for the successful healing outcome of apical microsurgery (AMS). The aim of the present in vitro study was to evaluate and compare the marginal adaptability of a novel calcium silicate cement (CSC), Harvard MTA Universal, and Biodentine used as root-end filling materials. The endodontic treatment of 20 extracted human maxillary central incisors was performed. The apicoectomy was simulated, and root-end cavities were prepared ultrasonically using universal retrotips. Teeth were randomly assigned into two equal groups (n = 10) according to the retrofilling cement used: Group 1—Harvard MTA Universal and Group 2—Biodentine. The specimens were stored in relative humidity for 48 h and sectioned longitudinally. The data were processed and analyzed statistically. Harvard MTA exhibited a significantly lower mean gap width (1.16 ± 0.37 µm) than Biodentine (2.48 ± 0.38 µm) (p < 0.05), indicating a more intimate interfacial adaptation. Additionally, the phenomenon of material penetration into the dentinal tubules was observed only in the Harvard MTA group. Within the limitations of this in vitro study, Harvard MTA Universal demonstrated better interfacial properties than Biodentine when applied as a root-end filling material. This novel biomaterial could be regarded as a promising alternative for earlier calcium silicate cements in the context of AMS goals. Clinical relevance: The quality of marginal adaptation is a determinative feature for the clinical performance of CSCs and the long-term prognosis of AMS. Full article

Background/Objectives. This manuscript presents an overview of advances in oncological radiotherapy as an effective treatment method for cancerous tumors, focusing on mechanisms of action within metabolite–antimetabolite systems. The urgency of this topic is underscored by the fact that cancer remains one of the leading causes of death worldwide: as of 2022, approximately 20 million new cases were diagnosed globally, accounting for about 0.25% of the total population. Given prognostic models predicting a steady increase in cancer incidence to 35 million cases by 2050, there is an urgent need for the latest developments in physics, chemistry, molecular biology, pharmacy, and strict adherence to oncological vigilance. The purpose of this work is to demonstrate the relationship between the nature and mechanisms of past diagnostic and therapeutic oncology approaches, their current improvements, and future prospects. Particular emphasis is placed on isotope technologies in the production of therapeutic nuclides, focusing on the mechanisms of formation of simple and complex theranostic compounds and their classification according to target specificity. Methods. The methodology involved searching, selecting, and analyzing information from PubMed, Scopus, and Web of Science databases, as well as from available official online sources over the past 20 years. The search was structured around the structure–mechanism–effect relationship of active pharmaceutical ingredients (APIs). The manuscript, including graphic materials, was prepared using a narrative synthesis method. Results. The results present a sequential analysis of materials related to isotope technology, particularly nucleus stability and instability. An explanation of theranostic principles enabled a detailed description of the action mechanisms of radiopharmaceuticals on various receptors within the metabolite–antimetabolite system using specific drug models. Attention is also given to radioactive nanotheranostics, exemplified by the mechanisms of action of radioactive nanoparticles such as Tc-99m, AuNPs, wwAgNPs, FeNPs, and others. Conclusions. Radiotheranostics, which combines the diagnostic properties of unstable nuclei with therapeutic effects, serves as an effective adjunctive and/or independent method for treating cancer patients. Despite the emergence of resistance to both chemotherapy and radiotherapy, existing nuclide resources provide protection against subsequent tumor metastasis. However, given the unfavorable cancer incidence prognosis over the next 25 years, the development of “preventive” drugs is recommended. Progress in this area will be facilitated by modern medical knowledge and a deeper understanding of ligand–receptor interactions to trigger apoptosis in rapidly proliferating cells. Full article

In the Karaganda coal basin, deteriorating geomechanical conditions have been observed, including seam disturbances, diminished strength of argillite–aleurolite strata, water ingress, and pronounced floor heave, all of which markedly increase the labor intensity of maintaining developmental headings. The maintenance and operation of these entries for a reference coal yield of 1000 t necessitate 72–75 man-shifts, of which 90–95% are expended on mitigating ground pressure effects and restoring support integrity. Conventional heave control measures—such as relief drifts, slotting, drainage, secondary blasting, and the application of concrete or rock–bolt systems—deliver either transient efficacy or incur prohibitive labor and material expenditures while lacking unified methodologies for predictive forecasting and support parameter design. This study therefore advocates for an integrated framework that synergizes geomechanical characterization, deformation prognosis, and the tailored selection of reinforcement schemes (incorporating both sidewall and floor-anchoring systems with directed preloading), calibrated to seam depth, geometry, and lithological properties. Employing deformation state assessments to optimize reinforcement layouts for floor stabilization in coal mine workings is projected to curtail repair volumes by 30–40% whilst significantly enhancing operational safety, efficiency, and the punctuality of face preparation. Full article

Background/Objectives: Melanoma is an aggressive skin cancer with high metastatic potential and poor prognosis in advanced stages. Hesperidin, a natural flavonoid, has shown anticancer properties across various malignancies. This study aimed to evaluate the antiproliferative and pro-apoptotic effects of Hesperidin, alone and in combination with Cisplatin, on the human epidermoid carcinoma cell line A431. Materials and Methods: A431 cells were cultured under standard conditions and treated with different concentrations of Hesperidin and Cisplatin for 48 h. Cell viability was assessed using the MTT assay. Apoptosis was evaluated by Annexin V-FITC/PI staining and caspase-3/7 activity assays. Expression levels of Bax, caspase-3/7, and survivin were measured by RT-qPCR. Results: Hesperidin significantly reduced cell viability at both 24 and 48 h. Annexin V/PI staining revealed increased apoptosis, with the highest apoptotic ratio in the Hesperidin + Cisplatin group (p < 0.001). Caspase-3/7 activity was markedly elevated in Hesperidin-treated cells. RT-qPCR showed upregulation of Bax and caspase-3/7 and downregulation of survivin. Conclusions: Hesperidin demonstrated significant cytotoxic and pro-apoptotic effects in A431 cells. When combined with Cisplatin, a synergistic enhancement of apoptosis was observed. These findings support the potential of Hesperidin as a complementary agent in carcinoma therapy, pending further in vivo and clinical validation. Full article

Colorectal cancer poses a significant threat to human health due to its high aggressiveness and poor prognosis. Key factors impacting patient outcomes include post-surgical recurrence, chemotherapeutic drug resistance, and insensitivity to immunotherapy. Consequently, early diagnosis and the development of effective targeted therapies are essential for improving prevention and treatment strategies. Inorganic nanomaterials have gained prominence in the diagnosis and treatment of colorectal cancer owing to their unique size, advantageous properties, and high modifiability. Various types of inorganic nanomaterials—such as metal-based, metal oxide, quantum dots, magnetic nanoparticles, carbon-based, and rare-earth nanomaterials—have demonstrated significant potential in enhancing multimodal imaging, drug delivery, and synergistic therapies. These advancements underscore their critical role in improving therapeutic outcomes. This review highlights the properties and development of inorganic nanomaterials, summarizes their recent applications and progress in colorectal cancer diagnosis and treatment, and discusses the challenges in translating these materials into clinical use. It aims to provide valuable insights for future research and the clinical application of inorganic nanomaterials in colorectal cancer management. Full article

Background and Objectives: Acute pancreatitis (AP) is an inflammatory disease where there is autodigestion of the pancreas by prematurely activated enzymes which may lead to a systemic inflammatory response. The aim of our study was to investigate the levels of circulating serum leukotriene B4 (LTB4), lipoxin A4 (LXA4), and resolvin D1 (RvD1) in pancreatitis due to gallstones in the etiologic investigation of AP. Materials and Methods: A total of 147 patients with AP (n: 49), AC (n: 49), and combined AP + AC (n: 49) will be included in the study. Healthy volunteers (n: 49) will be included as the control group. Results: RvD1 levels were significantly lower in patient groups compared to controls, while LXA4 levels were lower in patients with combined AP + AC (145.24 ng/L) compared to both controls (312.36 ng/L) and other patient groups. LTB4 levels were elevated in all patient groups compared to controls (335.56 ng/L vs. 65.56 ng/L) and were highest in combined AP + AC. Significant correlations were identified: RvD1 showed a negative correlation with LTB4 (r =−0.676; p < 0.001) and a positive correlation with LXA4 (r = 0.563, p < 0.001). ROC analysis demonstrated high diagnostic accuracy, with LXA4 and LTB4 achieving perfect differentiation (AUC: 1.0) between control and combined AP + AC cases. Conclusions: Our study showed that serum RvD1 and LXA4 levels have powerful anti-inflammatory properties in accordance with the literature. LTB4 may represent new, effective indicators to predict the severity of AP and the presence of necrosis in patients with AP. Despite its low sensitivity and specificity, RvD1 could be used as a complementary marker to the current scoring systems for the initial assessment of AP prognosis. These findings provide a new mechanistic understanding of how RvD1 attenuates inflammation to facilitate resolution, which could help develop novel therapeutic strategies for diseases caused by unresolved inflammation. It is easily obtainable and can provide additional prognostic information to clinicians. Full article

Hyaluronan (HA) is a ubiquitous macromolecule in the human body with remarkable structure and function. HA presents a key role in several biological processes in mammals. The synthesis/catabolism of HA is critical in several pathologies and has been used as a marker for the prognosis of cancers. Among its physiological roles, HA is used for wound healing applications. This review reports many of the latest developments of hyaluronan and its derivatives in research, preclinical, and published clinical trials for wound healing. An adequate physico-chemical characterization and identification of selected physico-chemical properties of the prepared material are mandatory. Moreover, cytotoxicity and evaluation of biological effects in vitro using standardized protocols are required as preclinical. Finally, to choose adequate in vivo models for testing efficacy is requested. Unfortunately, the biological role of HA is still not well understood. Therefore, an overview of several HA-based products is provided and discussed. Several ways of HA chemical modification were evaluated. Finally, this review focuses on products containing HA, novel developments, gaps, and limitations of the current state of the art. Full article

The increased early hydration rate of high early strength cement has economic advantages in many civil engineering fields (faster formwork removal or earlier demoulding of precast elements). Styrene–butadiene rubber (SBR) latex is the most common polymer in aqueous dispersions suitable for admixing in cement-based materials. It allows the designing of structures with specific properties for a variety of applications. The analysis of literature sources has shown that different properties of SBR latex-modified cement-based material samples reported were usually measured at 3, 7, 14, and 28 days of hardening. In this research, the authors decided to investigate a combined effect of high early strength Portland cement, characterized by an increased hydration rate, and SBR latex able to retard this process for a prolonged hardening period—up to 90 days in modified mortar samples. This study covers the results of the effect of different amounts of SBR latex (5%, 10%, 15%, and 20%) on the properties of modified mortar samples with a constant water-to-cement ratio prepared with high early strength Portland cement 42.5 R. The mortar samples were prepared from local raw materials produced by the Lithuanian companies. The properties, such as dry bulk density, ultrasonic pulse velocity, capillary water absorption, compressive and flexural strengths, and toughness, after three different hardening periods (7, 28, and 90 days) of the mortar samples were investigated. The applied mathematical–statistical methods allowed a detailed prognosis of the dependence between the dry bulk density and the strength properties of modified mortar samples. The combination of 42.5 R strength class Portland cement with the SBR latex in amounts ranging from 5% to 20% seems to be suitable for designing durable structures with specific properties. Full article

Objective: We assessed the changes in optical properties and biocompatibility of transition zones in multilayered translucent monolithic zirconia exposed to prolonged hydrothermal aging and compared the results to those with different yttrium oxide contents. Materials and Methods: Four types of zirconia blocks from IPS e.max ZirCAD were used: 3Y-TZP e.max ZirCAD LT (ZL), 4Y-TZP e.max ZirCAD MT (ZM), 5Y-TZP e.max ZirCAD MT Multi (ZT), and 3Y/5Y-TZP e.max ZirCAD Prime (ZP). A total of 120 specimens (15.0 mm diameter and 1.5 mm height) were fabricated and divided into three groups (n = 10). The aging process for the specimens was conducted in an autoclave set to 134 °C and 0.2 MPa, with durations of 0 h (control), 5 h (first aged), and 10 h (second aged). The optical properties and biocompatibility were analyzed, followed by a statistical analysis of the data (α = 0.05). Results: Before and after aging, ZL and ZP exhibited the lowest color changes. ZT exhibited the highest average transmittance and translucency parameter values, while ZL had the lowest. The water contact angle test showed the highest value in ZM and lowest in ZL across all the aging stages. ZL, ZM, and ZP showed a considerable decrease in the water contact angle; however, ZT did not. A cell counting kit-8 assay showed ZL had the highest value, while ZM had the lowest. A filamentous actin test exhibited the highest value in ZL and lowest in ZM. In the vinculin analysis, ZL and ZT exhibited the lowest values, whereas ZM and ZP had the highest. Conclusion: 3Y/5Y-TZP exhibited a balanced performance across critical parameters, such as color stability, translucency, and biocompatibility, aligning with 3Y-TZP. While 5Y-TZP demonstrated superior translucency, it confirmed the lowest color stability, whereas 3Y-TZP achieved the highest biocompatibility. These properties provide clinicians with a reliable material option that ensures superior esthetic outcomes and long-term prognosis, ultimately contributing to improved patient satisfaction and clinical longevity. Full article

Introduction: Apical periodontitis (AP) is an inflammatory disease of the periapical tissues that is often asymptomatic and diagnosed through radiographic examination. A challenge in traditional endodontics is disinfection of the root canal system (RCS), which anatomically presents numerous variations, often leading to persistent infections. Antimicrobial photodynamic therapy (aPDT) and photobiomodulation therapy (PBMT) offer promising adjuncts, due to their antimicrobial and tissue-healing properties. Objective: The aim of this article was to report five cases of teeth with pulp necrosis and asymptomatic apical periodontitis (AAP) treated with aPDT and PBMT protocols. Materials and Methods: Five cases of pulp necrosis and AAP were treated with conventional endodontic therapy supplemented with aPDT and PBMT. The treatment protocol included chemomechanical preparation (CMP), aPDT using a 660 nm diode laser (DL) with methylene blue (MB) as a photosensitizer (5 min pre-irradiation time), and PBMT using a 940 nm DL. Treatment results were evaluated through cone-beam computed tomography (CBCT)-based evaluation over 1 year of clinical follow-up. Results: All cases showed significant bone regeneration and tissue healing, demonstrating the efficacy of the combination of aPDT and PBMT. Post-operative pain did not occur in any of the patients, suggesting a possible analgesic effect of PBMT. Conclusions: The combination of aPDT and PBMT in endodontic therapy promoted tissue recovery and improved the prognosis of AAP. Further research and randomized control trials are needed to optimize treatment protocols and evaluate the long-term effects. Full article

In reconstructive surgery following partial mandibulectomy, the biomechanical integrity of the fibula free flap applied to the remaining mandibular region directly influences the prognosis of the surgery. The purpose of this study is to evaluate the biomechanical integrity of two fixation materials [titanium (Ti) and hydroxyapatite/poly-L-lactide (HA-PLLA)]. In this study, we simulated the mechanical properties of miniplate and screw fixations in two different systems by finite element analysis. A three-dimensional mandibular model was constructed and a fibula free flap and reconstruction surface were designed. The anterior and posterior end of the free flap was positioned with two miniplates and two additional miniplates were applied to the angled area of the fibula. The masticatory loading was applied considering seven principal muscles. The peak von Mises stress (PVMS) distribution, size of fixation deformation, principal stresses on bones, and gap opening size were measured to evaluate the material properties of the fixation. In the evaluation of properties, superior results were observed with both fixation methods immediately after surgery. However, after the formation of callus between bone segments at 2 months, the performance of Ti fixation decreased over time and the differences between the two fixations became minimal by 6 months after surgery. The result of the study implies the positive clinical potential of the HA-PLLA fixation system applied in fibula free flap reconstruction. Full article

The literature presents insufficient data evaluating the displacement and micromotion effects resulting from the combined use of tooth-implant connections in fixed partial dentures. Analyzing the biomechanical behavior of tooth-implant fixed partial denture (FPD) prothesis is vital for achieving an optimum design and successful clinical implementation. The objective of this study was to determine the relative significance of connector design on the displacement and micromotion of tooth-implant-supported fixed dental prostheses under occlusal vertical loading. A unilateral Kennedy class I mandibular model was created using a 3D reconstruction from CT scan data. Eight simulated designs of tooth-implant fixed partial dentures (FPDs) were split into two groups: Group A with rigid connectors and Group B with non-rigid connectors. The models were subjected to a uniform vertical load of 100 N. Displacement, strain, and stress were computed using finite element analysis. The materials were defined as isotropic, homogeneous, and exhibiting linear elastic properties. This study focused on assessing the maximum displacement in various components, including the bridge, mandible, dentin, cementum, periodontal ligament (PDL), and implant. Displacement values were predominantly higher in Group B (non-rigid) compared to Group A (rigid) in all measured components of the tooth-implant FPDs. Accordingly, a statistically significant difference was observed between the two groups at the FPD bridge (p value = 0.021 *), mandible (p value = 0.021 *), dentin (p value = 0.043 *), cementum (p value = 0.043 *), and PDL (p value = 0.043 *). Meanwhile, there was an insignificant increase in displacement values recorded in the distal implant (p value = 0.083). This study highlighted the importance of connector design in the overall stability and performance of the prosthesis. Notably, the 4.7 mm × 10 mm implant in Group B showed a displacement nearly 92 times higher than its rigid counterpart in Group A. Overall, the 5.7 mm × 10 mm combination of implant length and diameter showcased the best performance in both groups. The findings demonstrate that wider implants with a proportional length offer greater resistance to displacement forces. In addition, the use of rigid connection design provides superior biomechanical performance in tooth-implant fixed partial dentures and reduces the risk of micromotion with its associated complications such as ligament overstretching and implant overload, achieving predictable prognosis and enhancing the stability of the protheses. Full article