Search Results (12)

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

Glioblastoma is believed to be one of the most aggressive brain tumors in the world. ONX-0914 (PR957) is a selective inhibitor of proteasome subunit beta type-8 (PSMB8). Previous studies have shown that inhibiting PSMB8 expression in glioblastoma reduces tumor progression. Therefore, this study aimed to determine whether ONX-0914 has antitumor effects on human glioblastoma. The results indicated that ONX-0914 treatment inhibited survival in LN229, GBM8401, and U87MG glioblastoma cells. Cell cycle analysis showed that ONX-0914 treatment caused cell cycle arrest at the G1 phase and apoptosis in glioblastoma cells. The protein expression of BCL-2 was reduced and PARP was cleaved after ONX-0914 treatment. Furthermore, the levels of p53 and phosphorylated p53 were increased by ONX-0914 treatment in glioblastoma cells. ONX-0914 also induced autophagy in glioblastoma cells. Furthermore, the p53 inhibitor pifithrin attenuated apoptosis but enhanced autophagy caused by ONX-0914. In an orthotopic mouse model, TMZ plus ONX-0914 reduced tumor progression better than the control or TMZ alone. These data suggest that ONX-0914 is a novel therapeutic drug for glioblastoma. Full article

Proteasomes are intracellular structures responsible for protein degradation. The 20S proteasome is a core catalytic element of the proteasome assembly. Variations of catalytic subunits generate different forms of 20S proteasomes including immunoproteasomes (iPs), which are present mostly in the immune cells. Certain cells of the immune system are primary targets of retroviruses. It has been shown that several viral proteins directly affect proteasome functionality, while inhibition of proteasome activity with broad specificity proteasome inhibitors stimulates viral transduction. Here we specifically addressed the role of the immunoproteasomes during early stages of viral transduction and investigated the effects of specific immunoproteasome inhibition and activation prior to infection using a panel of cell lines. Inhibition of iPs in hematopoietic cells with immunoproteasome-specific inhibitor ONX-0914 resulted in increased infection by VSV-G pseudotyped lentiviruses. Moreover, a tendency for increased infection of cloned cells with endogenously decreased proteasome activity was revealed. Conversely, activation of iPs by IFN-γ markedly reduced the viral infectivity, which was rescued upon simultaneous immunoproteasome inhibition. Our results indicate that immunoproteasome activity might be determinative for the cellular antiretroviral resistance at least for the cells with high iP content. Finally, therapeutic application of immunoproteasome inhibitors might promote retroviral infection of cells in vivo. Full article

Duchenne muscular dystrophy (DMD) is a severe muscle-wasting disease. Although the lack of dystrophin protein is the primary defect responsible for the development of DMD, secondary disease complications such as persistent inflammation contribute greatly to the pathogenesis and the time-dependent progression of muscle destruction. The immunoproteasome is a potential therapeutic target for conditions or diseases mechanistically linked to inflammation. In this study, we explored the possible effects of ONX-0914 administration, an inhibitor specific for the immunoproteasome subunit LMP7 (ß5i), on motor performance, muscular pathology and protein degradation in 7-week old MDX mice, an age when the dystrophic muscles show extensive degeneration and regeneration. ONX-0914 (10 mg/kg) was injected subcutaneously on Day 2, 4, and 6. The mice were evaluated for physical performance (walking speed and strength) on Day 1 and 8. We show that this short-term treatment of ONX-0914 in MDX mice did not alter strength nor walking speed. The physical performance findings were consistent with no change in muscle inflammatory infiltration, percentage of central nuclei and proteasome content. Taken together, muscle structure and function in the young adult MDX mouse model are not altered with ONX-0914 treatment, indicating the administration of ONX-0914 during this critical time period does not exhibit any detrimental effects and may be an effective treatment of secondary complications of muscular dystrophy after further investigations. Full article

Inhibition of proteasome function by small molecules is highly efficacious in cancer treatment. Other than non-selective proteasome inhibitors, immunoproteasome-specific inhibitors allow for specific targeting of the proteasome in immune cells and the profound anti-inflammatory potential of such compounds revealed implications for inflammatory scenarios. For pathogen-triggered inflammation, however, the efficacy of immunoproteasome inhibitors is controversial. In this study, we investigated how ONX 0914, an immunoproteasome-selective inhibitor, influences CoxsackievirusB3 infection in NMRI mice, resulting in the development of acute and chronic myocarditis, which is accompanied by formation of the immunoproteasome in heart tissue. In groups in which ONX 0914 treatment was initiated once viral cytotoxicity had emerged in the heart, ONX 0914 had no anti-inflammatory effect in the acute or chronic stages. ONX 0914 treatment initiated prior to infection, however, increased viral cytotoxicity in cardiomyocytes, promoting infiltration of myeloid immune cells into the heart. At this stage, ONX 0914 completely inhibited the β5 subunit of the standard cardiac proteasome and less efficiently blocked its immunoproteasome counterpart LMP7. In conclusion, ONX 0914 unselectively perturbs cardiac proteasome function in viral myocarditis of NMRI mice, reduces the capacity of the host to control the viral burden and promotes cardiac inflammation. Full article