Search Results (19)

Background and Objectives: Diabetes mellitus (DM) is frequently associated with impaired wound healing due to persistent oxidative stress, chronic inflammation, and dysregulated proteasome activity, leading to delayed tissue repair and increased risk of chronic ulcers. The present study aimed to investigate the role of the immunoproteasome system in diabetic wound healing, with a particular focus on its involvement in oxidative stress and inflammatory pathways, and to evaluate whether pharmacological inhibition with ONX-0914 improves tissue repair. Materials and Methods: Experimental diabetes was induced in rats using streptozotocin (STZ), and the animals were allocated to three groups: healthy control, STZ-induced diabetic, and STZ + ONX-0914 treatment. Wound healing was evaluated by macroscopic analysis of wound closure and histopathological examination at days 3, 7, and 14. Oxidative stress and antioxidant status were assessed by measuring malondialdehyde (MDA) levels and antioxidant enzyme activities (SOD, CAT, and GSH-Px) in serum and wound tissues. Proteasome activity was analyzed fluorometrically, while systemic and local inflammatory responses were determined by ELISA and Western blot analysis of IL-1β, TNF-α, and IL-6. Results: STZ-induced diabetes significantly delayed wound closure, increased lipid peroxidation, reduced antioxidant enzyme activities, and elevated systemic and tissue inflammatory cytokine levels. Treatment with ONX-0914 markedly accelerated wound closure and improved histological healing parameters, including re-epithelialization, granulation tissue formation, and angiogenesis. Moreover, ONX-0914 significantly reduced MDA levels while restoring SOD, CAT, and GSH-Px activities in both serum and wound tissues. The treatment also inhibited proteasome activity and significantly suppressed the expression of IL-1β, TNF-α, and IL-6. Conclusions: ONX-0914 significantly improves diabetic wound healing by restoring antioxidant defenses, reducing oxidative damage, and attenuating inflammatory signaling pathways. These findings suggest that immunoproteasome inhibition represents a promising therapeutic strategy for enhancing tissue repair in diabetic conditions. Full article

Additive manufacturing using vat photopolymerization (VPP) resin materials has gained attention for fabricating dental prostheses; however, the effects of material type and build angle on their properties remain unclear. We compared the mechanical properties of two filler-containing VPP hybrid resins, SprintRay Ceramic Crown (CC) and OnX Tough 2 (OT), with those of a conventional polymethyl methacrylate (PMMA) disc material, and evaluated the influence of build angle on surface characteristics, dimensional accuracy, and mechanical performance. Specimens were fabricated using a DLP system at build angles of 0°, 45°, and 90°. Vickers hardness, surface morphology and roughness, dimensional deviations, flexural strength, elastic modulus, and fracture energy were assessed according to relevant standards. CC exhibited significantly higher hardness and elastic modulus than PMMA and OT, whereas OT showed the highest fracture energy. Surface morphology and roughness were strongly affected by build angle, with 45° producing distinct periodic patterns and increased roughness. Dimensional evaluation revealed a tendency toward overbuilding, particularly in the vertical direction at 45°. Flexural properties were also influenced by build angle, with 45° generally providing favorable performance. Both material composition and build angle affect VPP-fabricated dental resin performance, highlighting the importance of appropriate material and processing selection for clinical applications. Full article

Background: The choice of mechanical prosthesis for mitral valve replacement (MVR) is critical, yet data comparing long-term outcomes across different valve types are still needed. This study aimed to compare the long-term clinical and echocardiographic outcomes of four distinct mechanical mitral valve prostheses. Methods: We retrospectively analyzed 431 patients who underwent mechanical MVR between 2009 and 2022 with one of four valve types: Carbomedics (n = 112), Bicarbon (n = 176), ATS (n = 89), or On-X (n = 54). A competing risk regression model was used to identify predictors of a composite endpoint (valve thrombosis, reoperation, stroke, pulmonary embolism, and major bleeding), accounting for all-cause mortality. Longitudinal echocardiographic data were analyzed using linear mixed-effects models. Results: The median follow-up was 62 months. The cumulative incidence of the composite endpoint at 10 years was 14% for the On-X valve, 12% for the Bicarbon valve, 9.5% for the Carbomedics valve, and 7% for the ATS valve. After adjusting for confounders, the type of valve prosthesis was not significantly associated with the composite endpoint. Significant predictors of adverse events included coronary artery disease (Sub-distribution Hazard Ratio [SHR] 2.70, p = 0.023), peripheral artery disease (SHR 6.29, p = 0.007), and smaller valve size (SHR 0.87, p = 0.037). No significant difference in overall survival was observed between the groups (log-rank p = 0.904). All valve types were associated with favorable LV remodeling. The Carbomedics group showed the greatest reduction in left ventricular end-diastolic diameter, likely reflecting regression to the mean given the larger baseline ventricular dimensions in this group. Conclusions: The type of mechanical mitral valve did not significantly influence long-term thromboembolic and bleeding events or overall survival. Patient-specific factors and valve size were the primary determinants of adverse outcomes. The observed differences in ventricular remodeling may warrant further investigation. Full article

Background/Objectives: Fully digital workflows used in implant dentistry have been evolving to improve rehabilitation times and patient satisfaction. More studies are necessary for full scientific validation. The aim of this study was to evaluate the 6-month outcome of implant-supported fixed prostheses for full edentulism rehabilitation using OnX Tough 2 resin (SprintRay) and the Pro 2 (SprintRay) 3D printer following the All-on-4 concept. Methods: This study included 16 patients (10 female, 6 male) with 20 implant-supported fixed full-arch prostheses following the All-on-4 concept (10 rehabilitations for each stackable guide and photogrammetry protocols). Primary The primary outcome measure was implant and prosthetic survival. The secondary outcome measures included manufacturing issues, prosthetic passive fit, marginal bone loss (MBL), mechanical and biological complications, modified plaque and bleeding indexes, pocket depths, patient subjective evaluation, and the Oral Health Impact Profile. Results: No patients were lost to follow-up. Two prostheses failed and 2 two implants were lost, resulting in a cumulative survival rate of 90% and 97.5% at 6 months for prostheses and implants, respectively. The mean MBL was 0.31 mm ± 0.52 mm at 4 months. The mechanical complications rate was 50% at patient level. One patient (6.3%) experienced one biological complication. The grades regarding “comfort of prostheses in the mouth” and “overall chewing feeling” were 9.35 ± 1.29 and 8.79 ± 1.67 out of 10, respectively. The mean total sum of the OHIP-14 was 1.61 out of 56. Conclusions: Implant-supported full-arch rehabilitations with fixed prostheses following the All-on-4 concept, through a fully digital workflow protocol, are a viable option in the short term. Full article

This study evaluated the effect of acidic environment and tooth brushing on the color stability and translucency of stained 3D-printed ceramic-reinforced composite (CRC) resins for indirect restorations and hybrid prostheses. Twelve specimens were prepared from each 3D-printing resin material: Ceramic Crown (CC), OnX (ONX), and Tough 2 (T2), and one CAD/CAM milling resin, Lava Ultimate (LU). After preparation, all specimens were stained, then immersed in either water or citric acid. Subsequently, the specimens underwent simulated tooth brushing for 3650 cycles. Color stability (ΔE) and translucency parameter (TP) were measured using a spectrophotometer. Data were analyzed using ANOVA, post hoc Tukey tests, and independent Student t-tests (α = 0.05). Material type, immersion medium, and their interaction did not significantly influence the mean ΔE (p > 0.05). The lowest ΔE value was for LU in acid (ΔE = 1.11 ± 0.39), and the highest for T2 in water (ΔE = 2.09 ± 1.47). Except for ONX and LU in acid, all materials had ΔE values above the perceptibility threshold (ΔE = 1.2). The mean TP was significantly affected by material type, immersion medium, and their interaction (p < 0.05). The lowest TP value was for group CC in acid (0.91 ± 0.26); the highest was for group LU in acid (6.24 ± 0.56). After immersion and subsequent tooth brushing, TP values decreased for all materials. Exposure to an acidic environment and tooth brushing did not affect color stability but significantly reduced translucency. Both the 3D-printed CRCs and milled resin material displayed comparable color stability below clinically acceptable thresholds, though the translucency of 3D-printed materials remained lower compared to milled material. Full article

Skeletal muscle pathologies, including sarcopenia, inflammatory myopathies, and various muscular dystrophies, are strongly influenced by chronic low-grade inflammation and impaired proteostasis. Immunoproteasomes (IMPs), inducible proteolytic complexes activated by pro-inflammatory cytokines, are emerging as regulators linking immune signaling to protein quality control. Evidence suggests that IMPs have paradoxical, context-dependent roles in skeletal muscle. On one hand, they can support proteostasis and muscle regeneration under stress; on the other, persistent activation may sustain cytokine production, antigen presentation, and maladaptive immune–muscle interactions, promoting chronic inflammation and muscle wasting. Selective IMP inhibitors, such as ONX 0914 and KZR-616, display potent anti-inflammatory effects in preclinical models of autoimmune myositis and muscle atrophy. Yet, their use in skeletal muscle pathologies is controversial; while inhibition may dampen harmful immune activation, it could also impair muscle repair and proteostasis. This review summarizes current findings, highlights key contradictions, and explores unresolved questions about the role of IMPs in skeletal muscle pathologies. We emphasize the need for a deeper understanding of IMP-mediated mechanisms in skeletal muscle pathology and strategies combining selective inhibitors to enhance therapeutic efficacy while minimizing adverse effects. IMPs thus represent both a promising and potentially risky therapeutic target, with outcomes highly dependent on disease context. Full article

This study aimed to assess the effect of acidic storage and simulated brushing on the translucency and color stability of 3D-printed resins for prosthodontic applications. Three 3D printed resin materials—Ceramic Crown (CC), OnX (ONX), and Tough 2 (T2)—were compared with a CAD/CAM milled nano-ceramic resin material (Lava Ultimate, LU). Twelve specimens were fabricated from each material and were allocated into two groups based on the storage medium (water or citric acid), followed by simulated tooth brushing for 3650 cycles. The specimens’ translucency (TP) and color stability (ΔE) were determined using a spectrophotometer. The data was compared using ANOVA, independent student t-tests, and a post hoc Tukey test (p < 0.05). Multiple comparisons of mean differences in TP revealed significant differences between the tested materials (p < 0.001), except for groups CC and ONX. Irrespective of the groups, all materials showed decreased TP values after simulated tooth brushing. Regarding color stability, CC (0.66 ± 0.42) and T2 (1.40 ± 0.34) in acid demonstrated the least and greatest color changes, respectively. The ΔE did not vary between the materials or between the storage media (p > 0.05). Except for T2 and LU in water, the other materials showed ΔE values below the perceptibility threshold of 1.2. The material type and storage media affected the translucency of the tested materials. However, regardless of the material type and storage media, there was no discernible impact on the color change of the tested materials. Full article

The aim of this study was to evaluate and compare the surface roughness and gloss—both initially and after simulated toothbrushing—of three 3D-printed crown materials subjected to different surface treatments: varnishing, polishing with diamond-impregnated rubber polishers, and polishing with a bristle brush and paste. Disc-shaped specimens (n = 90) were 3D-printed using three commercially available crown resins (Rodin Sculpture, VarseoSmile TriniQ, and OnX Tough 2) and post-processed per manufacturers’ instructions. Specimens were divided into three surface treatment groups: application of a light-cured varnish, polishing with a two-step diamond-impregnated rubber polisher, or polishing with a bristle brush and abrasive paste. Surface roughness and gloss were measured after treatment and again following 20,000 cycles of simulated toothbrushing. Additional specimens were prepared for Vickers microhardness testing and determination of filler weight percentage (wt%). Statistical comparisons were performed using two-way ANOVA with significance set at p < 0.05. Results: The varnish provided the statistically lowest roughness of all surface treatments for all materials. The bristle brush and abrasive paste polishing protocol produced the greatest gloss for the softest material (VarseoSmile TriniQ) and lowest gloss for the hardest material (Rodin Sculpture), whereas the two-step diamond-impregnated rubber polisher produced an equivalent gloss on all materials. Following toothbrushing, roughness was minimally affected; however, gloss was considerably reduced. Conclusions: All tested polishing and varnishing methods achieved clinically acceptable surface roughness (Ra < 0.2 µm) that persisted after simulated toothbrushing. Notably, the two-step diamond-impregnated rubber polisher produced consistent gloss across all materials, while the bristle brush and abrasive paste polishing protocol performed better on softer materials, and varnish application resulted in equal or superior gloss and roughness retention compared to polishing. Full article

Background: The ”respect” approach to surgical mitral valve repair, which involves implanting artificial neochordae, is gaining increased adoption. Surgeons are possibly prone to error in the manual construction of neochordae, which can lead to prolonged cross-clamp times. Novel systems such as Chord-X Pre-Measured Loops (On-X Life Technologies, Inc., Austin, TX, USA) eliminate the need for manual neochordae construction, potentially simplifying the mitral repair procedure. However, clinical data on its use are currently limited to a small publication. Methods: We conducted a retrospective cohort study to evaluate the use of Chord-X loops in 40 consecutive patients who underwent surgery in Geelong, Victoria, Australia, between May 2020 and February 2024. Three surgeons participated in this study. Results: All patients were referred for severe mitral valve regurgitation secondary to myxomatous degeneration, with P2 prolapse being the most common pathology. Chord-X Pre-Measured Loops effectively corrected a variety of leaflet pathologies, including bi-leaflet disease, with a single set of loops sufficing in most patients. Intraoperative and follow-up echocardiographic assessments revealed no greater than mild mitral regurgitation in any patient, with 75% exhibiting no or trace mitral regurgitation. Conclusions: The Chord-X Pre-Measured Loops system demonstrated safety, efficacy, and reproducibility across all patients. Surgeons were able to easily adopt this technology without requiring additional training. We believe this technology offers a safe option for surgeons performing low-volume mitral repair surgeries. Full article

The mechanical valve was first invented in the 1950s, and since then, a wide variety of prostheses have been developed. Although mechanical valves have outstanding durability, their use necessitates life-long treatment with anticoagulants, which increases the risk of bleeding and thromboembolic events. The current guidelines recommend a mechanical prosthetic valve in patients under 50–60 years; however, for patients aged 50–70 years, the data are conflicting and there is not a clear-cut recommendation. In recent decades, progress has been made in several areas. First, the On-X mechanical valve was introduced; this valve has a lower anticoagulant requirement in the aortic position. Second, a potential alternative to vitamin K-antagonist treatment, rivaroxaban, has shown encouraging results in small-scale trials and is currently being tested in a large randomized clinical trial. Lastly, an innovative mechanical valve that eliminates the need for anticoagulant therapy is under development. We attempted to review the current literature on the subject with special emphasis on the role of mechanical valves in the current era and discuss alternatives and future innovations. Full article

Hemophiliacs can develop cardiovascular diseases, including valvulopathies of various etiologies and severities. Some require surgical treatment. Performing cardiac surgery in hemophiliacs is a challenge because they maintain an increased risk of bleeding throughout their lives. Our review shows that with a multidisciplinary team and careful planning, cardiac surgery can be safely performed in these patients. Valve repair and bioprosthetic valves should be preferred over mechanical valves to avoid life-long anticoagulation. In patients who cannot receive a bioprosthetic valve, the use of the On-X mechanical valve might be considered because it requires less intensive anticoagulation after 3 months of treatment. Antithrombotic treatment is feasible in hemophiliacs only if the coagulation factor level is kept constantly above a specific trough limit. Our review is valuable because, for the first time, the available data on the modern surgical treatment of valvular disease in hemophiliacs have been synthesized and systematized. Full article

Background: Determination of the eligibility of several tooth analog materials for use in crown fracture testing. Methods: A standardized premolar crown preparation was replicated into three types of resin dies (C&B, low modulus 3D printed resin; OnX, high modulus 3D printed resin composite; and highest modulus milled resin composite). 0.8 mm zirconia crowns were bonded to the dies and the maximum fracture load of the crowns was tested. Twelve extracted human premolars were prepared to a standardized crown preparation, and duplicate dies of the prepared teeth were 3D printed out of C&B. Zirconia crowns were bonded to both the dies and natural teeth, and their fracture load was tested. Results: There was no statistical difference between the fracture load of zirconia crowns bonded to standardized dies of C&B (1084.5 ± 134.2 N), OnX (1112.7 ± 109.8 N) or Lava Ultimate (1137.5 ± 88.7 N) (p = 0.580). There was no statistical difference between the fracture load of crowns bonded to dentin dies (1313 ± 240 N) and a 3D-printed resin die (C&B, 1156 ± 163 N) (p = 0.618). Conclusions: There was no difference in the static fracture load of zirconia crowns bonded to standardized resin dies with different moduli or between a low modulus resin die and natural dentin die. Full article

Healing in compromised and complicated bone defects is often prolonged and delayed due to the lack of bioactivity of the fixation device, secondary infections, and associated oxidative stress. Here, we propose amorphous silicon oxynitride (SiON_x) as a coating for the fixation devices to improve both bioactivity and bacteriostatic activity and reduce oxidative stress. We aimed to study the effect of increasing the N/O ratio in the SiON_x to fine-tune the cellular activity and the antioxidant effect via the NRF2 pathway under oxidative stress conditions. The in vitro studies involved using human mesenchymal stem cells (MSCs) to examine the effect of SiON_x coatings on osteogenesis with and without toxic oxidative stress. Additionally, bacterial growth on SiON_x surfaces was studied using methicillin-resistant Staphylococcus aureus (MRSA) colonies. NRF2 siRNA transfection was performed on the hMSCs (NRF2-KD) to study the antioxidant response to silicon ions. The SiON_x implant surfaces showed a >4-fold decrease in bacterial growth vs. bare titanium as a control. Increasing the N/O ratio in the SiON_x implants increased the alkaline phosphatase activity >1.5 times, and the other osteogenic markers (osteocalcin, RUNX2, and Osterix) were increased >2-fold under normal conditions. Increasing the N/O ratio in SiON_x enhanced the protective effects and improved cell viability against toxic oxidative stress conditions. There was a significant increase in osteocalcin activity compared to the uncoated group, along with increased antioxidant activity under oxidative stress conditions. In NRF2-KD cells, there was a stunted effect on the upregulation of antioxidant markers by silicon ions, indicating a role for NRF2. In conclusion, the SiON_x coatings studied here displayed bacteriostatic properties. These materials promoted osteogenic markers under toxic oxidative stress conditions while also enhancing antioxidant NRF2 activity. These results indicate the potential of SiON_x coatings to induce in vivo bone regeneration in a challenging oxidative stress environment. Full article

Proteasomes degrade most intracellular proteins. Several different forms of proteasomes are known. Little is known about the role of specific proteasome forms in the central nervous system (CNS). Inhibitors targeting different proteasome forms are used in clinical practice and were shown to modulate long-term potentiation (LTP) in hippocampal slices of untreated animals. Here, to address the role of non-constitutive proteasomes in hippocampal synaptic plasticity and reveal the consequences of their continuous inhibition, we studied the effect of chronic administration of the non-constitutive proteasome inhibitor ONX-0914 on the LTP induced by two different protocols: tetanic stimulation and theta-burst stimulation (TBS). Both the tetanus- and TBS-evoked potentiation contribute to the different forms of hippocampal-dependent memory and learning. Field-excitatory postsynaptic potentials (fEPSPs) in hippocampal slices from control animals and animals treated with DMSO or ONX-0914 were compared. LTP induced by the TBS was not affected by ONX-0914 administration; however, chronic injections of ONX-0914 led to a decrease in fEPSP slopes after tetanic stimulation. The observed effects correlated with differential expression of genes involved in synaptic plasticity, glutaminergic synapse, and synaptic signaling. Obtained results indicate that non-constitutive proteasomes are likely involved in the tetanus-evoked LTP, but not the LTP occurring after TBS, supporting the relevance and complexity of the role of specific proteasomes in synaptic plasticity, memory, and learning. Full article

Muscle wasting is a major pathological feature observed in Duchenne muscular dystrophy (DMD) and is the result of the concerted effects of inflammation, oxidative stress and cell senescence. The inducible form of proteasome, or immunoproteasome (IP), is involved in all the above mentioned processes, regulating antigen presentation, cytokine production and immune cell response. IP inhibition has been previously shown to dampen the altered molecular, histological and functional features of 3-month-old mdx mice, the animal model for DMD. In this study, we described the role of ONX-0914, a selective inhibitor of the PSMB8 subunit of immunoproteasome, in ameliorating the pathological traits that could promote muscle wasting progression in older, 9-month-old mdx mice. ONX-0914 reduces the number of macrophages and effector memory T cells in muscle and spleen, while increasing the number of regulatory T cells. It modulates inflammatory markers both in skeletal and cardiac muscle, possibly counteracting heart remodeling and hypertrophy. Moreover, it buffers oxidative stress by improving mitochondrial efficiency. These changes ultimately lead to a marked decrease of fibrosis and, potentially, to more controlled myofiber degeneration/regeneration cycles. Therefore, ONX-0914 is a promising molecule that may slow down muscle mass loss, with relatively low side effects, in dystrophic patients with moderate to advanced disease. Full article