12 research outputs found
A computed tomographic evaluation of effect of mandibular advancement device at two different horizontal jaw positions in patients with obstructive sleep apnea
Statement of problem: Studies pertaining to the objective assessments of the efficacy of mandibular advancement device in patients with obstructive sleep apnea are scarce. Purpose: The purpose of this clinical study was to evaluate the effect of MAD at two different horizontal positions of mandible on upper airway dimensions through computed tomography. Material and methods: Twenty-nine consenting participants satisfying predetermined inclusion and exclusion criteria were enrolled and an adjustable two-piece MAD was fabricated at 50% maximum mandibular protrusion and after 4 weeks was adjusted to 70% protrusion. CT scans were obtained at baseline, 4 weeks after delivering MAD with 50% mandibular protrusion, and then after 4 weeks with 70% mandibular protrusion. Cross sectional area with diameters (lateral and anteroposterior) of upper airway was measured at three specific anatomic levels (retropalatal-RP, retroglossal-RG, and epiglottal-EG). Data were analyzed using the Student t-test for parametric analysis. Results: Intragroup comparison revealed a statistically significant increase in lateral & anteroposterior dimensions as well as cross sectional area at all three anatomical levels at 4 weeks after MAD with 50% mandibular protrusion compared with baseline and 4 weeks after MAD with 70% mandibular protrusion compared with baseline. However, the difference between lateral and anteroposterior dimensions with MAD at 70% protrusion compared with MAD at 50% protrusion was not statistically significant. The difference between cross-sectional area was found to be statistically significant. Conclusion: Mandibular advancement device at 70% mandibular protrusion is more effective compared with the device at 50% protrusion in relieving oropharyngeal obstruction seen in OSA
Downregulation of solute carrier family 4 members 4 as a biomarker for colorectal cancer
Abstract Colorectal cancer (CRC) is one of the major cancer types associated with increased mortality worldwide. Hence, identifying reliable biomarkers make it very essential for early diagnosis and prognosis of CRC. Numerous studies have been conducted to decipher molecular mechanisms underlying CRC, however more deep insightful knowledge is the need of the hour. The purpose of this study was to identify promising key candidate genes in colorectal cancer (CRC) and assess their expression and clinical significance. To clarify and verify promising key biomarkers with signal transduction pathways in colorectal cancer, we integrated 11 microarray datasets from NCBI-GEO. This study utilized multiple bioinformatics tools and databases, including OncoDB, GEO2R, UALCAN, GEIPA, TIMER, and DAVID. The gene expression profiles of eleven datasets (GSE10714, GSE113513, GSE13471, GSE15960, GSE24514, GSE32323, GSE41258, GSE4183, GSE44076, GSE44861, GSE9348) were screened. In 11 gene expression profiles, 3 downregulated genes were identified and validated by databases such as OncoDB, UALCAN, GEIPA and TIMER. Downregulation of SLC4A4 with significant predictive value was validated by multi-omic data analysis and validated by Gene Expression Omnibus (GEO). GEIPA survival analysis showed that low SLC4A4 expression correlated with poorer overall survival among CRC patients. Based on this study, we identified SLC4A4 as a potential candidate biomarker for colorectal cancer (CRC), enabling early diagnosis and prognosis with molecular targeted therapy
Targeting SLC4A4: A Novel Approach in Colorectal Cancer Drug Repurposing
Background: Colorectal cancer (CRC) is a complex and increasingly prevalent malignancy with significant challenges in its treatment and prognosis. This study aims to explore the role of the SLC4A4 transporter as a biomarker in CRC progression and its potential as a therapeutic target, particularly in relation to tumor acidity and immune response. Methods: The study utilized computational approaches, including receptor-based virtual screening and high-throughput docking, to identify potential SLC4A4 inhibitors. A model of the human SLC4A4 structure was generated based on CryoEM data (PDB ID 6CAA), and drug candidates from the DrugBank database were evaluated using two computational tools (DrugRep and CB-DOCK2). Results: The study identified the compound (5R)-N-[(1r)-3-(4-hydroxyphenyl)butanoyl]-2-decanamide (DB07991) as the best ligand, demonstrating favorable binding affinity and stability. Molecular dynamics simulations revealed strong protein–ligand interactions with consistent RMSD (~0.25 nm), RMSF (~0.5 nm), compact Rg (4.0–3.9 nm), and stable SASA profiles, indicating that the SLC4A4 structure remains stable upon ligand binding. Conclusions: The findings suggest that DB07991 is a promising drug candidate for further investigation as a therapeutic agent against CRC, particularly for targeting SLC4A4. This study highlights the potential of computational drug repositioning in identifying effective treatments for colorectal cancer
