Search Results (613)

Background: Soft tissue sarcomas (STSs) are a rare and heterogeneous group of mesenchymal tumors with limited response to current therapies, particularly in advanced stages. STS tumors were traditionally considered “cold” tumors, characterized by limited immune infiltration and low immunogenicity. However, emerging evidence is challenging this perception, highlighting a potentially critical role for the immune system in STS biology. Objective: Building on our previous findings suggesting impaired natural killer (NK) cell activity in STS patients, we aimed to perform an in-depth characterization of peripheral NK cells in STS. Methods: Peripheral blood samples from STS patients and sex- and age-matched healthy donors were analyzed to assess NK cell degranulation, IFNγ production, and receptor repertoire. Results: Functional assays revealed a notable reduction in both degranulation and IFNγ production in NK cells from STS patients. STS patients also exhibited dysregulated expression of activating and inhibitory NK cell receptors. Principal component analysis (PCA) identified CD27 and NKp44 as critical markers for distinguishing STS patients from healthy donors. Increased CD27 expression represents a shift towards a more regulatory NK cell phenotype, and we found that CD27 expression was negatively correlated with NK cell degranulation and IFNγ production. ROC curve analysis demonstrated strong potential to distinguish between the groups for both CD27 (AUC = 0.85) and NKp44 (AUC = 0.94). Conclusion: In conclusion, STS patients exhibited impaired NK cell function, altered receptor repertoire, and a shift towards a less cytotoxic and more regulatory phenotype. Full article

In the context of critical challenges in curcumin-modified polyurethane synthesis—including limited curcumin bioavailability and suboptimal biodegradability/biocompatibility—a novel polyurethane material (Cur-PU) with good mechanical, shape memory, pH-responsive, and biocompatibility was synthesized via a one-pot, two-step synthetic protocol in which HO-PCL-OH served as the soft segment and curcumin was employed as the chain extender. The experimental results demonstrate that with the increase in Cur units, the crystallinity of the Cur-PU material decreases from 32.6% to 5.3% and that the intensities of the diffraction peaks at 2θ = 21.36°, 21.97°, and 23.72° in the XRD pattern gradually diminish. Concomitantly, tensile strength decreased from 35.5 MPa to 19.3 MPa, and Shore A hardness declined from 88 HA to 65 HA. These observations indicate that the sterically hindered benzene ring structure of Cur imposes restrictions on HO-PCL-OH crystallization, leading to lower crystallinity and retarded crystallization kinetics in Cur-PU. As a consequence, the material’s tensile strength and hardness are diminished. Except for the Cur-PU-3 sample, all other variants exhibited exceptional shape-memory functionality, with R_f and R_r exceeding 95%, as determined by three-point bending method. Analogous to pure curcumin solutions, Cur-PU solutions demonstrated pH-responsive chromatic transitions: upon addition of hydroxide ion (OH⁻) solutions at increasing concentrations, the solutions shifted from yellow-green to dark green and finally to orange-yellow, enabling sensitive pH detection across alkaline gradients. Hydrolytic degradation studies conducted over 15 weeks in air, UPW, and pH 6.0/8.0 phosphate buffer solutions revealed mass loss <2% for Cur-PU films. Surface morphological analysis showed progressive etching with the formation of micro-to-nano-scale pores, indicative of a surface-erosion degradation mechanism consistent with pure PCL. Biocompatibility assessments via L929 mouse fibroblast co-culture experiments demonstrated ≥90% cell viability after 72 h, while relative red blood cell hemolysis rates remained below 5%. Collectively, these findings establish Cur-PU as a biocompatible material with tunable mechanical properties, and pH responsiveness, underscoring its translational potential for biomedical applications such as drug delivery systems and tissue engineering scaffolds. Full article

Malignant Peripheral Nerve Sheath Tumors (MPNSTs) are a deadly subtype of soft tissue sarcoma for which effective therapeutic options are lacking. Currently, the best treatment for MPNSTs is complete surgical resection with wide negative margins, but this is often complicated by the tumor size and location and/or the presence of metastases. Radiation or chemotherapy may be combined with surgery, but patient responses are poor. Targeted treatments, including small-molecule inhibitors of oncogenic proteins such as mitogen-activated protein kinase kinase (MEK), cyclin-dependent kinases 4 and 6 (CDK4/6), and Src-homology 2 domain-containing phosphatase 2 (SHP2), are promising therapeutics for MPNSTs, especially when combined together, but they have yet to gain approval. Immunotherapeutic approaches have been revolutionary for the treatment of some other cancers, but their utility as single agents in sarcoma is limited and not approved for MPNSTs. The immunosuppressive niche of MPNSTs is thought to confer inherent treatment resistance, particularly to immunotherapies. Remodeling an inherently “cold” tumor microenvironment into a “hot” immune milieu to bolster the anti-tumor activity of immunotherapies is of great interest throughout the cancer community. This review focuses on novel therapeutics that target dysregulated factors and pathways in MPNSTs, as well as different types of immunotherapies currently under investigation for this disease. We also consider how certain therapeutics may be combined to remodel the MPNST immune microenvironment and thereby generate a durable anti-tumor immune response to immunotherapy. Full article

The anodic oxidation of titanium implants is a practical, cost-effective method to enhance implant success, especially due to rising hypersensitivity concerns. This study investigated the electrochemical behavior, surface characteristics, and biocompatibility of anodized commercially pure titanium (cpTi, grade IV). Anodization is performed on polished, cleaned cpTi sheet samples in 1 M H₂SO₄ using a constant voltage of 15 V for 15 and 45 min. The color of the oxide layer is evaluated using the CIELab color space, while composition is analyzed by a scanning electron microscope (SEM) equipped with an energy dispersive spectrometer (EDS). Additionally, X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) are performed to identify and monitor the phase transformations of the formed titanium oxides. Corrosion measurements are performed in 9 g L⁻¹ NaCl, pH = 7.4, and show the excellent corrosion stability of the anodized samples in comparison with pure titanium. The biological response is assessed by determining mitochondrial activity and gene expression in human fibroblasts. Anodized surfaces, particularly Ti-45, promote higher mitochondrial activity and the upregulation of adhesion-related genes (N-cadherin and Vimentin) in human gingival fibroblasts, indicating improved biocompatibility and the potential for enhanced early soft tissue integration. Full article

Rhabdomyosarcoma (RMS), the most common pediatric soft tissue sarcoma, comprises embryonal (ERMS) and alveolar (ARMS) subtypes with distinct histopathological features, clinical outcomes, and therapeutic responses. To better characterize their molecular distinctions, we performed untargeted plasma proteomics and metabolomics profiling in children with ERMS (n = 18), ARMS (n = 17), and matched healthy controls (n = 18). Differential expression, functional enrichment (GO, KEGG, RaMP-DB), co-expression network analysis (WGCNA/WMCNA), and multi-omics integration (DIABLO, MOFA) revealed distinct molecular signatures for each subtype. ARMS displayed elevated oncogenic and stemness-associated proteins (e.g., cyclin E1, FAP, myotrophin) and metabolites involved in lipid transport, fatty acid metabolism, and polyamine biosynthesis. In contrast, ERMS was enriched in immune-related and myogenic proteins (e.g., myosin-9, SAA2, S100A11) and metabolites linked to glutamate/glycine metabolism and redox homeostasis. Pathway analyses highlighted subtype-specific activation of PI3K-Akt and Hippo signaling in ARMS and immune and coagulation pathways in ERMS. Additionally, the proteomics and metabolomics datasets showed association with clinical parameters, including disease stage, lymph node involvement, and age, demonstrating clear molecular discrimination consistent with clinical observation. Co-expression networks and integrative analyses further reinforced these distinctions, uncovering coordinated protein–metabolite modules. Our findings reveal novel, subtype-specific molecular programs in RMS and propose candidate biomarkers and pathways that may guide precision diagnostics and therapeutic targeting in pediatric sarcomas. Full article

Background: Surface electromyography (sEMG) enables the non-invasive assessment of muscle activity and is widely used in orthodontics for evaluating masticatory muscles. However, little is known about the dynamic changes in facial expression muscles during orthodontic treatment. This study aimed to investigate alterations in facial muscle tone during the leveling and alignment phase in adult female patients undergoing fixed appliance therapy. Methods: The study included 30 female patients aged 20–31 years who underwent sEMG assessment at four time points: before treatment initiation (T0), at the start of appliance placement (T1), three months into treatment (T2), and six months into treatment (T3). Muscle activity was recorded during four standardized facial expressions: eye closure, nasal strain, broad smile, and lip protrusion. Electrodes were placed on the orbicularis oris, orbicularis oculi, zygomaticus major, and levator labii superioris alaeque nasi muscles. A total of 1440 measurements were analyzed using Friedman and Conover-Inman tests (α = 0.05). Results: Significant changes in muscle tone were observed during treatment. During lip protrusion, the orbicularis oris and zygomaticus major showed significant increases in peak and minimum activity (p < 0.01). Eye closure was associated with altered orbicularis oris activation bilaterally at T3 (p < 0.01). Nasal strain induced significant changes in zygomaticus and levator labii muscle tone, particularly on the right side (p < 0.05). No significant changes were noted during broad smiling. Conclusions: Orthodontic leveling and alignment influence the activity of selected facial expression muscles, demonstrating a dynamic neuromuscular adaptation during treatment. These findings highlight the importance of considering soft tissue responses in orthodontic biomechanics and suggest potential implications for facial esthetics and muscle function monitoring. Full article

Medical phantoms are essential to imaging calibration, clinician training, and the validation of therapeutic procedures. However, most ultrasound phantoms prioritize acoustic realism while neglecting the viscoelastic and anisotropic properties of fibrous soft tissues. This gap limits their effectiveness in modeling realistic biomechanical behavior, especially in wave-based diagnostics and therapeutic ultrasound. Current materials like gelatine and agarose fall short in reproducing the complex interplay between the solid and fluid components found in biological tissues. To address this, we developed a soft, anisotropic composite whose dynamic mechanical properties resemble fibrous biological tissues such as skin and skeletal muscle. This material enables wave propagation and vibration studies in controllably anisotropic media, which are rare and highly valuable. We demonstrate the tunability of damping and stiffness aligned with fiber orientation, providing a versatile platform for modeling soft-tissue dynamics and validating biomechanical simulations. The phantoms achieved Young’s moduli of 7.16–11.04 MPa for skin and 0.494–1.743 MPa for muscles, shear wave speeds of 1.51–5.93 m/s, longitudinal wave speeds of 1086–1127 m/s, and sound absorption coefficients of 0.13–0.76 dB/cm/MHz, with storage, loss, and complex moduli reaching 1.035–6.652 kPa, 0.1831–0.8546 kPa, and 2.138–10.82 kPa. These values reveal anisotropic response patterns analogous to native tissues. This novel natural fibrous composite system affords sustainable, low-cost ultrasound phantoms that support both mechanical fidelity and acoustic realism. Our approach offers a route to next-gen tissue-mimicking phantoms for elastography, wave propagation studies, and dynamic calibration across diverse clinical and research applications. Full article

A comprehensive framework for ultrasound imaging simulations is presented. Solutions to an inhomogeneous wave equation are provided, yielding a linear model for characterizing ultrasound propagation and scattering in soft tissue. This simulation approach, which is based upon the fast nearfield method, is implemented in the Fast Object-oriented C++ Ultrasound Simulator (FOCUS) and is extended to a range of imaging modalities, including synthetic aperture, B-mode, plane wave, and color Doppler imaging. The generation of radiofrequency (RF) data and the receive beamforming techniques employed for each imaging modality, along with background on color Doppler imaging, are described. Simulation results demonstrate rapid convergence and lower error rates compared to conventional spatial impulse response methods and Field II, resulting in substantial reductions in computation time. Notably, the framework effectively simulates hundreds of thousands of scatterers without the need for a full three-dimensional (3D) grid, and the inherent randomness in the scatterer distributions produces realistic speckle patterns. A plane wave imaging example, for instance, achieves high fidelity using 100,000 scatterers with five steering angles, and the simulation is completed on a personal computer in a few minutes. Furthermore, by modeling scatterers as moving particles, the simulation framework captures dynamic flow conditions in vascular phantoms for color Doppler imaging. These advances establish FOCUS as a robust, versatile tool for the rapid prototyping, validation, and optimization of both established and novel ultrasound imaging techniques. Full article

Both biosystems and engineering fields demand advanced friction-reducing and lubricating materials. Due to their hydrophilicity and tissue-mimicking properties, hydrogels are ideal candidates for use as lubricants in water-based environments. They are particularly well-suited for applications involving biocompatibility or interactions with intelligent devices such as soft robots. However, external environments, whether within the human body or in engineering applications, often present a wide range of dynamic conditions, including variations in shear stress, temperature, light, pH, and electric fields. Additionally, hydrogels inherently possess low mechanical strength, and their dimensional stability can be compromised by changes during hydration. This review focuses on recent advancements in using environmentally responsive hydrogels as lubricants. It explores strategies involving physical or structural modifications, as well as the incorporation of smart chemical functional groups into hydrogel polymer chains, which enable diverse responsive mechanisms. Drawing on both the existing literature and our own research, we also examine how composite friction materials where hydrogels serve as water-based lubricants offer promising solutions for demanding engineering environments, such as bearing systems in marine vessels. Full article

Skin and soft tissue infections (SSTIs) are becoming an urgent public health issue worldwide. The globe is facing a growing problem with drug-resistant germs, and current treatments are not quite cutting it. There is a real need for new therapies that can tackle these challenges more effectively. This brings us to an interesting question: Can extracellular vesicles (EVs) from different sources, such as mesenchymal stem cells (MSCs), immune cells, or even plants and animals, help in treating SSTIs, especially given the rise in drug resistance? Studies have shown that MSC-derived EVs are particularly noteworthy because they carry components such as antimicrobial peptides (AMPs) that can work together to fight infections, boost the immune response, and aid in healing. These vesicles play a role in how our body interacts with infections, helping to clear bacteria, reduce inflammation, and promote tissue repair. We also see that EVs from plants and bacteria can directly fight off germs, while those from animals can support the healing process of skin. Although early studies have shown promise for EV therapies, there are still hurdles to overcome, such as ensuring consistent production and delivery. This review looks at the potential of EVs as powerful agents in managing infections and supporting healing, highlighting an exciting area of research in medicine. Full article

Cardiovascular diseases are responsible for a large number of severe disability cases and deaths worldwide. Strong research in this field has been extensively carried out, in particular for the associated complications, such as the occlusion of small-diameter (<6 mm) vessels. Accordingly, in the present research, two random copolyesters of poly(butylene 2,5-furandicarboxylate) (PBF) and poly(butylene isophthalate) (PBI), were successfully synthesized via two-step melt polycondensation and were thoroughly characterized from molecular, thermal, and mechanical perspectives. The copolymeric films displayed a peculiar thermal behavior, being easily processable in the form of films, although amorphous, with T_g close to room temperature. Their thermal stability was high in all cases, and from the mechanical point of view, the materials exhibited a high ultimate strength, together with values of elastic moduli tunable with the chemical composition. The long-term stability of these materials under physiological conditions was also demonstrated. Cytotoxicity was assessed using a direct contact assay with human umbilical vein endothelial cells (HUVECs). In addition, hemocompatibility was tested by evaluating the adhesion of blood components (such as the adsorption of human platelets and fibrinogen). As a result, a proper chemical design and, in turn, both the solid-state and functional properties, are pivotal in regulating cell behavior and opening new frontiers in the tissue engineering of soft tissues, including vascular tissues. Full article

For many years, staphylococci have been detected mainly in infections of the skin and soft tissues, organs, bone inflammations, and generalized infections. Thromboembolic diseases have also become a serious plague of our times, which, as it turns out, are closely related to the toxic effects of staphylococci. Staphylococcus aureus, because of the presence of many different kinds of virulence factors, is capable of manipulating the host’s innate and adaptive immune responses. These include toxins and cofactors that activate host zymogens and exoenzymes, as well as superantigens, which are highly inflammatory and cause leukocyte death. Coagulases and staphylokinases can control the host’s coagulation system. Nucleases and proteases inactivate various immune defense and surveillance proteins, including complement components, peptides and antibacterial proteins, and surface receptors that are important for leukocyte chemotaxis. On the other hand, secreted toxins and exoenzymes are proteins that disrupt the endothelial and epithelial barrier as a result of cell lysis and disintegration of linking proteins, which ultimately increases the risk of thromboembolism. In this review, we discuss various virulence factors and substances that may inhibit their activity. Full article

Objectives: This study aimed to evaluate the effects of different titanium (Ti) anodized surfaces on soft tissue healing around dental implant abutments. Methods: Discs of machined (MC), pink anodized (PA) and yellow anodized (YA) surfaces were morphologically characterized and evaluated in vitro. Cell adhesion and collagen synthesis by human gingival fibroblasts (hGFs) were assessed to evaluate the regenerative potential of the surfaces under study. Their inflammatory potential was evaluated in THP-1 cell cultures by measuring cytokine secretion, and their proteomic adsorption patterns were characterized using nano-liquid chromatography mass spectrometry (nLC-MS/MS). Statistical significance was considered at 5%. In relation to proteomics, statistical differences were evaluated using the Student t-test with the Perseus application. Results: The anodization process resulted in a reduction in the surface roughness parameter (Ra) relative to the machined titanium (p < 0.05). No differences in hGF adhesion were found between the surfaces after one day. PA induced increased hGF collagen synthesis after 7 days (p < 0.05). The secretion of TNF-α was lower for anodized surfaces than for MC, and its concentration was lower for PA than for YA (p < 0.05). In turn, TGF-β was higher for PA and YA versus MC after one and three days of culture. A total of 176 distinct proteins were identified and 26 showed differences in adhesion between the anodized surfaces and MC. These differential proteins were related to coagulation, lipid metabolism, transport activity, plasminogen activation and a reduction in the immune response. Conclusions: Anodized Ti surfaces showed promising anti-inflammatory and regenerative potential for use in dental implant abutments. Anodization reduced surface roughness, increased collagen synthesis and lowered TNF-α secretion while increasing TGF-β levels compared to machined surfaces. Identified proteins related to coagulation and lipid metabolism supported these findings. Clinical relevance: Anodized surfaces could offer improved short-term peri-implant soft tissue healing over machined surfaces. The analysis of abutment surface, instead of implant surface, is a new approach that can provide valuable information. Full article

Implant primary stability is a prerequisite for obtaining osseointegration and clinical success. Insertion torque (IT) is measured during implant placement and is expressed in Ncm. It represents the quantification of the frictional force experienced by the implant as it progresses apically through a rotational motion along its axis. Usually, to achieve osseointegration, a value within the range of 20–40 Ncm is desirable. Below a threshold of 20 Ncm, implants have a decrease in survival rate, while implant stability is guaranteed above 20 Ncm. The main goal of this study was to evaluate whether high values of IT affect osseointegration, implant health, and healing, by highlighting the positive and negative effects of IT > 50 Ncm on peri-implant bone, soft tissues, and long-term stability. This scoping review considered randomized clinical trials, observational studies, and cohort studies. Studies failing to meet the predefined inclusion criteria were excluded from the analysis. The review process adhered to the Preferred Reporting Items for Scoping Reviews (PRISMA-ScR) guidelines. Ultimately, a total of 11 studies were included in the final synthesis. Based on the studies included, the literature suggests that high values of IT guarantee adequate primary stability and better osseointegration. However, high IT is significantly associated with greater marginal bone loss, depending on bone density. Accordingly, IT values > 50 Ncm may provoke greater compressive forces with a negative impact on the jawbone. An elevated strain on the bone can induce necrosis and ischemia, due to an alteration of circulation, which in turn is responsible for marginal bone loss and reduced osseointegration. Lack of osseointegration ultimately leads to an early implant failure. As concerns soft tissue recession, a higher decrease is measured in implants placed with high-insertion torque. Nonetheless, additional clinical trials are warranted to assess long-term outcomes, quantify the incidence of these complications, and explore the impact of emerging clinical variables. Full article

Recent developments in 3D bioprinting offer innovative alternative solutions to classical treatments for head and neck defects. Soft tissues in an anatomical area as diverse in composition as the head and neck are complex in terms of structure and function. Understanding how cellular interaction underlies functionality has led to the development of bioinks capable of mimicking the natural morphology and roles of different human parts. Moreover, from the multitude of recently developed materials, there are now many options for building scaffolds that potentiate the activity of these cells. The fidelity and accuracy of the utilized techniques ensure maximum precision in terms of model construction. Emerging technologies will allow for improved control of the scaffold, facilitating optimal results in the treatment of various pathologies, without concerns about the availability of donors, immunological response, or any other side effects that traditional treatments withhold. This paper explores the current landscape of bioprinted scaffolds and their applications in the head and neck region, with a focus on the properties and use of natural and synthetic bioinks in the attempt to replicate the biomechanical features of native tissues. Customization capabilities that support anatomical precision and biofunctionality are also addressed. Moreover, regulatory requirements, as well as current challenges related to biocompatibility, immune response, and vascularization, are critically discussed in order to provide a comprehensive overview of the pathway to clinical application. Full article