Nanoparticle Augmentation of Adhesive Systems: Impact on Tensile Strength in Fiberglass Post Placement within Root Dentin.

BACKGROUND Modification of the glass fiber post (GFP) with titanium dioxide or silver particles can improve the durability and reliability of dental treatments for ensuring long-term success. This research assessed the tensile bond strength (TBS) of an adhesive system used for cementing GFPs into root dentin following the incorporation of nanoparticles of titanium dioxide (NTiO2) and silver (NAg). MATERIAL AND METHODS Sixty human maxillary canines were prepared to create a 10-mm intra-radicular space for post placement from the cementoenamel junction. The specimens were randomly allocated into 2 groups (a non-thermocycling group and a thermocycling group). Each group was divided into 3 subgroups (10 samples each) according to the adhesive system used (adhesive system devoid of any addition, adhesive system including 1% NAg, and adhesive system infused with 1% NTiO2). TBS tests were conducted and recorded in MPa using a Universal Testing Machine, with an axial load applied at a rate of 0.5 mm/min until failure. The TBS for both groups (non-thermocycling and thermocycling) was measured in megapascals (MPa), and the failure type was recorded. The data were statistically analyzed using one-way analysis of variance (ANOVA) and Tukey's test with P.

Relationship between Deep Marginal Elevation and Periodontal Parameters: A Systematic Review.

Background and Objectives: This review focuses on reviewing studies from the literature regarding the effects of deep margin elevation on the surrounding periodontium. Materials and Methods: A review of the literature was carried out using the following online databases: Embase, The Cochrane Library, MEDLINE-PubMed and Google Scholar. Our search was limited to articles from 2010 to 2023. The search terms consisted of keywords and MeSH terms, which were 'deep margin elevation', 'coronal margin relocation', 'periodontium' and 'periodontal tissues'. The literature was searched thoroughly by two reviewers. Initially, the titles of the articles were extracted. After removing irrelevant and duplicate articles, abstracts were assessed for relevant articles. Finally, the reviewers analyzed full-text articles. Results: A total of twelve articles, including one randomized clinical trial, three systematic reviews, two prospective cohort, three case series, one a clinical study, one pilot study and one a retrospective study, were selected and analyzed. Conclusions: The review suggests potential benefits of Deep Margin Elevation (DME) over surgical crown lengthening due to reduced invasiveness, yet conclusive effects on periodontal tissue remain unclear, warranting further studies on clinical parameters and inflammatory biomarkers.

Mitochondrial Import of Dengue Virus NS3 Protease and Cleavage of GrpEL1, a Cochaperone of Mitochondrial Hsp70.

Dengue virus infections, which have been reported in nearly 140 countries, pose a significant threat to human health. The genome of dengue virus encodes three structural and seven nonstructural (NS) proteins along with two untranslated regions, one each on both ends. Among them, dengue protease (NS3) plays a pivotal role in polyprotein processing and virus multiplication. NS3 is also known to regulate several host proteins to induce and maintain pathogenesis. Certain viral proteins are known to interact with mitochondrial membrane proteins and interfere with their functions, but the association of a virus-coded protein with the mitochondrial matrix is not known. In this report, by using in silico analysis, we show that NS3pro alone is capable of mitochondrial import; however, this is dependent on its innate mitochondrial transport signal (MTS). Transient-transfection and protein import studies confirm the import of NS3pro to the mitochondrial matrix. Similarly, NS3pro-helicase (amino acids 1 to 464 of NS3) also targets the mitochondria. Intriguingly, reduced levels of matrix-localized GrpE protein homolog 1 (GrpEL1), a cochaperone of mitochondrial Hsp70 (mtHsp70), were noticed in NS3pro-expressing, NS3pro-helicase-expressing, and virus-infected cells. Upon the use of purified components, GrpEL1 undergoes cleavage, and the cleavage sites have been mapped to KR81A and QR92S. Importantly, GrpEL1 levels are seriously compromised in severe dengue virus-infected clinical samples. Our studies provide novel insights into the import of NS3 into host mitochondria and identify a hitherto unknown factor, GrpEL1, as a cleavage target, thereby providing new avenues for dengue virus research and the design of potential therapeutics.IMPORTANCE Approximately 40% of the world's population is at risk of dengue virus infection. There is currently no specific drug or potential vaccine for these infections. Lack of complete understanding of the pathogenesis of the virus is one of the hurdles that must be overcome in developing antivirals for this virus infection. In the present study, we observed that the dengue virus-coded protease imports to the mitochondrial matrix, and our report is the first ever of a virus-coded protein, either animal or human, importing to the mitochondrial matrix. Our analysis indicates that the observed mitochondrial import is due to an inherited mitochondrial transport signal. We also show that matrix-localized GrpE protein homolog 1 (GrpEL1), a cochaperone of mitochondrial Hsp70 (mtHsp70), is also the substrate of dengue virus protease, as observed in vitro and ex vivo in virus-infected cells and dengue virus-infected clinical samples. Hence, our studies reveal an essential aspect of the pathogenesis of dengue virus infections, which may aid in developing antidengue therapeutics.

Nuclear Transcription Factors in the Mitochondria: A New Paradigm in Fine-Tuning Mitochondrial Metabolism.

Noncanonical functions of several nuclear transcription factors in the mitochondria have been gaining exceptional traction over the years. These transcription factors include nuclear hormone receptors like estrogen, glucocorticoid, and thyroid hormone receptors: p53, IRF3, STAT3, STAT5, CREB, NF-kB, and MEF-2D. Mitochondria-localized nuclear transcription factors regulate mitochondrial processes like apoptosis, respiration and mitochondrial transcription albeit being nuclear in origin and having nuclear functions. Hence, the cell permits these multi-stationed transcription factors to orchestrate and fine-tune cellular metabolism at various levels of operation. Despite their ubiquitous distribution in different subcompartments of mitochondria, their targeting mechanism is poorly understood. Here, we review the current status of mitochondria-localized transcription factors and discuss the possible targeting mechanism besides the functional interplay between these factors.

The import of the transcription factor STAT3 into mitochondria depends on GRIM-19, a component of the electron transport chain.

The signal transducer and activator of transcription 3 (STAT3), a nuclear transcription factor, is also present in mitochondria and regulates cellular respiration in a transcriptional-independent manner. The mechanism of STAT3 import into mitochondria remains obscure. In this report we show that mitochondrial-localized STAT3 resides in the inner mitochondrial membrane. In vitro import studies show that the gene associated with retinoid interferon induced cell mortality 19 (GRIM-19), a complex I subunit that acts as a chaperone to recruit STAT3 into mitochondria. In addition, GRIM-19 enhances the integration of STAT3 into complex I. A S727A mutation in STAT3 reduces its import and assembly even in the presence of GRIM-19. Together, our studies unveil a novel chaperone function for GRIM-19 in the recruitment of STAT3 into mitochondria.

Intelligence computational analysis of letrozole solubility in supercritical solvent via machine learning models.

Supercritical fluids (SCFs) can be used to prepare drugs nanoparticles with improved solubility. SCFs have shown superior advantages in pharmaceutical industry as an environmentally friendly alternative to toxic/harmful organic solvents. They possess gas-like transport characteristics and liquid-like solvation power for solutes. Evaluation of chemotherapeutic drugs' solubility in supercritical carbon dioxide (SCCO2) has been recently an attractive subject for developing this method in pharmaceutical sector. To reach this purpose, the utilization of accurate models is of great necessity to estimate experimental-based solubility data. In this paper, the authors tried to employ machine learning (ML) approaches to estimate the solubility of Letrozole (LET) drug as chemotherapeutic agent and correlate its values in wide ranges of temperature and pressure. To do this, PAR (Passive Aggressive Regression), RF (Random Forest), and RBF-SVM are the models used (Support Vector Machine with RBF kernel). These models optimized in terms of their hyper-parameters using GA algorithm. The optimized PAR, RF, RBF-SVM models obtained coefficients of determination (R-squared) of 0.8277, 0.9534, and 0.9947. Also, the MSE error rate of the models are 0.1342, 0.0305, and 0.0045, in the same order. The final result of the evaluations shows the optimized RBF-SVM model as the most appropriate model in this research. The model exhibits a maximum prediction error of 0.1289.

Decreased anterograde transport coupled with sustained retrograde transport contributes to reduced axonal mitochondrial density in tauopathy neurons.

Mitochondria are essential organelle required for neuronal homeostasis. Mitochondria supply ATP and buffer calcium at synaptic terminals. However, the complex structural geometry of neurons poses a unique challenge in transporting mitochondria to synaptic terminals. Kinesin motors supply mitochondria to the axonal compartments, while cytoplasmic dynein is required for retrograde transport. Despite the importance of presynaptic mitochondria, how and whether axonal mitochondrial transport and distribution are altered in tauopathy neurons remain poorly studied. In the current study, we have shown that anterograde transport of mitochondria is reduced in P301L neurons, while there is no change in the retrograde transport. Consistently, axonal mitochondrial abundance is reduced in P301L neurons. We further studied the possible role of two opposing motor proteins on mitochondrial transport and found that mitochondrial association of kinesin is decreased significantly in P301L cells. Interestingly, fitting our experimental data into mathematical equations suggested a possible rise in dynein activity to maintain retrograde flux in P301L cells. Our data indicate that decreased kinesin-mediated transport coupled with sustained retrograde transport might reduce axonal mitochondria in tauopathy neurons, thus contributing to the synaptic deficits in Alzheimer's disease (AD) and other tauopathies.

Comparison and Advanced Antimicrobial Strategies of Silver and Copper Nanodrug-Loaded Glass Ionomer Cement against Dental Caries Microbes.

Caries lesions during cement repairs are a severe issue, and developing a unique antimicrobial restorative biomaterial can help to reduce necrotic lesion recurrence. As a result, Thymus vulgaris extract was used to biosynthesize copper nanoparticles (TVE-CuNPs) exhibiting different characteristics (TVE). Along with TVE-CuNPs, commercial silver nanoparticles (AgNPs) and metronidazole were combined with glass ionomer cement (GIC) to test its antibacterial efficacy and compressive strength. FTIR, XRD, UV-Vis spectrophotometry, and TEM were applied to characterize the TVE-CuNPs. Additionally, AgNPs and TVE-CuNPs were also combined with metronidazole and GIC. The modified GIC samples were divided into six groups, where groups 1 and 2 included conventional GIC and GIC with 1.5% metromidazole, respectively; group 3 had GIC with 0.5% TVE-CuNPs, while group 4 had 0.5% TVE-CuNPs with metronidazole in 1.5%; group 5 had GIC with 0.5% AgNPs, and group 6 had 0.5% AgNPs with metronidazole at 1.5%. An antimicrobial test was performed against Staphylococcus aureus (S. aureus) and Streptococcus mutans (S. mutans) by the disc diffusion method and the modified direct contact test (MDCT). GIC groups 4 and 6 demonstrated a greater antimicrobial efficiency against the two tested strains than the other groups. In GIC groups 4 and 6, the combination of GIC with two antimicrobial agents, 1.5% metronidazole and 0.5% TVE-CuNPs or AgNPs, enhanced the antimicrobial efficiency when compared to that of the other groups with or without a single agent. GIC group specimens combined with nanosilver and nanocopper had similar mean compressive strengths when compared to the other GIC groups. Finally, the better antimicrobial efficacy of GIC boosted by metronidazole and the tested nanoparticles against the tested strains may be relevant for the future creation of more efficient and modified restorations to reduce dental caries lesions.

Appropriateness use criteria for transthoracic echocardiography: relationship with radiology benefit managers preauthorization determination and comparison of the new (2010) criteria to the original (2007) criteria.

BACKGROUND: In response to growth in cardiac imaging, medical societies have published appropriateness use criteria (AUC) and payers have introduced preauthorization mandates, largely through radiology benefits managers (RBM). The correlation of algorithms used to determine preauthorization with the AUC is unknown. In addition, studies applying the 2007 AUC for transthoracic echocardiography revealed that many echocardiograms could not be classified. We sought to examine the impact of the revised 2010 AUC on appropriateness ratings of transthoracic echocardiograms previously classified by the 2007 AUC and the relationship of preauthorization determination to AUC rating. METHODS: We reclassified indications for transthoracic echocardiography as appropriate, inappropriate, uncertain, or unclassifiable using the 2010 AUC in the same 625 patients previously reported using 2007 AUC. We also evaluated the relationship between preauthorization status by 2 RBM precertification algorithms and appropriateness rating by 2007 AUC. RESULTS: The appropriateness classification of 148 (24%) transthoracic echocardiograms was changed by the updated AUC (P < .001). The number of unclassifiable echocardiograms was markedly reduced from 99 (16%) to 8 (1%), and more echocardiograms were classified as inappropriate (95 [15%] vs 45 [7%]) or uncertain (43 [7%] vs 0 [0%]). Limited correlation between the 2007 AUC rating and RBM preauthorization determinations was noted, with only moderate agreement with RBM no. 1 (90%, κ = 0.480, P < .001) and poor agreement with RBM no. 2 (72%, κ = 0.177, P < .001). CONCLUSION: The updated AUC (2010) provide enhanced clinical value compared with 2007 AUC. There is limited agreement between RBM preauthorization determination and 2007 AUC rating.

Rotenone-induced reactive oxygen species signal the recruitment of STAT3 to mitochondria.

STAT3, a transcription factor involved in various physiological and pathological processes, is also present in mitochondria. Mitochondrial STAT3 regulates complex I activity and reactive oxygen species (ROS) production, yet the mechanisms governing its translocation to mitochondria remain poorly understood. In this study, we show that rotenone-induced ROS triggers the Ser727 phosphorylation of STAT3 and its increased mitochondrial localisation. Furthermore, we show that STAT3-depleted cells display increased ROS levels during rotenone treatment. Targeted expression in mitochondria of wild-type STAT3 - but not S727A mutant - lowers ROS levels, indicating the importance of Ser727 phosphorylation, both in rotenone-induced mitochondrial targeting and quenching of ROS levels. Together, our results demonstrate a novel STAT3-mediated feedback mechanism to maintain redox homeostasis during stress.

Adherence to appropriateness criteria for transthoracic echocardiography: comparisons between a regional department of Veterans Affairs health care system and academic practice and between physicians and mid-level providers.

We compared adherence to appropriateness criteria for transthoracic echocardiography in a Veterans Administration Medical Center (VAMC) and an academic practice and, within the VAMC, between physicians and mid-level providers. We reviewed 201 outpatient echocardiograms performed in the laboratory of an academic practice and 424 outpatient and inpatient studies performed at a VAMC. Echocardiographic examinations requested for indications addressed in the criteria were considered classified, and those for indications not addressed were considered unclassified. Classified studies were further rated as appropriate or inappropriate. Of 625 echocardiograms reviewed, 99 (16%) were unclassified. Approximately 80% of the indications for these could be assigned to 4 categories. Of the remaining 526 echocardiograms, indications were appropriate in 481 (91.4%) and inappropriate in 45 (8.6%). Among classified outpatient studies at the VAMC, mid-level providers requested significantly more studies for inappropriate indications than physicians (16.0% vs 7%, P = .024). There was no significant difference in the frequency of outpatient studies requested for inappropriate indications by VAMC and academic practice physicians (7.0% vs 9.5%, P = .558). The appropriateness criteria perform reasonably well at evaluating variations in use of echocardiography between health care systems and providers. The large majority of studies are requested for appropriate indications, although there is room for improvement.