Αρχειοθήκη ιστολογίου

Αλέξανδρος Γ. Σφακιανάκης
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5
Άγιος Νικόλαος Κρήτη 72100
2841026182
6032607174

Τρίτη 6 Δεκεμβρίου 2022

Helicobacter pyhlori regulated microRNA map of human gastric cells

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Abstract

Background

Helicobacter pylori is an infection of concern for its chronic colonization leading to peptic ulcers and gastric cancer. In recent times, microRNAs have been extensively studied to understand their role in the pathogenesis of this bacteria in diverse contexts of gastric diseases. The current analysis reports the microRNA-mRNA interactions that are associated with effective survival and virulence of this pathogen.

Materials and Methods

We convened differentially regulated human microRNAs responsive to H. pylori infection (HP-hDEmiRs) at different multiplicity of infection and time points in human gastric cell lines through retrospective data mining of experimental studies. In view of the molecular disparity of clinical samples and animal models, data from tissue, serum/plasma, urine, and ascites were excluded. Further, we utilized diverse bioinformatics approaches to retrieve experimentally validated, high-confidence targets of the HP-hDEmiRs to analyze the microRNA-mRNA interactions that are relevant to H. pylori pathogenesis.

Results

A total of 39 HP-hDEmiRs that showed unidirectional expression of either overexpression or downregulation were identified to modulate 23 targets explicitly studied under this infection. We also identified 476 experimentally validated targets regulated by at least 4 of the HP-hDEmiRs. In addition to the pathways prior-associated with H. pylori infection, the microRNA-mRNA interactome analysis identified several cellular processes and pathways highly associated with cell cycle, cell division, migration, and carcinogenesis.

Conclusion

This study generated a platform to study the mechanisms utilized by this pathogen using microRNAs as surrogate.

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Traditional versus conservative endodontic access impact on fracture resistance of chairside CAD‐CAM lithium disilicate anterior crowns: An in vitro study

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Abstract

Purpose

To evaluate the effect of traditional and conservative endodontic access hole preparation on fracture resistance of chairside computer-aided design and computer-aided manufacturing (CAD-CAM) lithium disilicate maxillary right central incisor crowns.

Materials and Methods

Fifty-seven milled lithium disilicate maxillary right central incisor crowns were designed and fabricated with a chairside CAD-CAM system (Planmeca Romexis, Planmeca). The abutment preparation had a 1.0 mm incisal reduction and 1.0 mm chamfer finish. The restorations were bonded with resin cement to printed resin dies (n = 19 per group) and were treated and divided into three groups, 1) no endodontic access, 2) traditional triangular endodontic access, and 3) conservative ovoidal endodontic access. The endodontic access of the crowns was sealed with flowable resin composite. Restorations were subjected to 10,000 cycles of thermal cycling between 5° and 55°C. Then, restorations were loaded and exposed to compressive loading force, and the crack initiation (CI) and complete fracture (CF) were recorded. SEM micrographs of broken specimens on the printed dies were captured. ANOVA test and Bonferroni's correction were used for statistical comparison.

Results

The fracture resistance among the three groups varied. Crowns with no endodontic access displayed significantly (p < 0.001) higher resistance [CI: 1025 (121) N; CF 1134 (127) N], followed by crowns with conservative ovoidal endodontic access [CI: 924 (60) N; CF: 1000 (72) N. Crowns with traditional triangular endodontic access showed the significantly (p < 0.001) lowest fracture resistance [CI: 635 (82) N; CF: 709 (75) N].

Conclusion

The fracture resistance of chairside CAD-CAM lithium disilicate maxillary anterior crowns is influenced by the type of endodontic access provided. Conservative ovoidal endodontic access provides crowns with higher fracture resistance than traditional triangular endodontic access. Crowns with no endodontic access provided the highest resistance than other types of endodontic access.

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Trotabresib, an oral potent bromodomain and extraterminal inhibitor, in patients with high-grade gliomas: a phase I, “windowofopportunity” study

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Abstract
Background
The bromodomain and extraterminal protein (BET) inhibitor trotabresib has demonstrated antitumor activity in patients with advanced solid tumors, including high-grade gliomas. CC-90010-GBM-001 (NCT04047303) is a phase I study investigating the pharmacokinetics, pharmacodynamics, and CNS penetration of trotabresib in patients with recurrent high-grade gliomas scheduled for salvage resection.
Methods
Patients received trotabresib 30 mg/day on days 1–4 before surgery, followed by maintenance trotabresib 45 mg/day 4 days on/24 days off after surgery. Primary endpoints were plasma pharmacokinetics and trotabresib concentrations in resected tissue. Secondary and exploratory endpoints included safety, pharmacodynamics, and antitumor activity.
Results
Twenty patients received preoperative trotabresib and underwent resection with no delays or cancellations of surgery; 16 patients received maintenance trot abresib after recovery from surgery. Trotabresib plasma pharmacokinetics were consistent with previous data. Mean trotabresib brain tumor tissue:plasma ratio was 0.84 (estimated unbound partition coefficient [KPUU] 0.37), and modulation of pharmacodynamic markers was observed in blood and brain tumor tissue. Trotabresib was well tolerated; the most frequent grade 3/4 treatment-related adverse event during maintenance treatment was thrombocytopenia (5/16 patients). Sixmonth progression-free survival was 12%. Two patients remain on treatment with stable disease at cycles 25 and 30.
Conclusions
Trotabresib penetrates the blood–brain-tumor barrier in patients with recurrent high-grade glioma and demonstrates target engagement in resected tumor tissue. Plasma pharmacokinetics, blood pharmacodynamics, and safety were comparable with previous results for trotabresib in patients with advanced solid tumors. Investigation of adjuvant trotabresib + temozolomide and concom itant trotabresib + temozolomide + radiotherapy in patients with newly diagnosed glioblastoma is ongoing (NCT04324840).
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