Molecular modeling of novel 2-aminopyridine derivatives as potential JAK2 inhibitors: a rational strategy for promising anticancer agents.

Janus kinase 2(JAK2) is a potential target for anticancer drugs in the treatment of numerous myeloproliferative diseases due to its central role in the JAK/STAT signaling cascade. In this study, the binding behavior of 2 amino-pyridine derivatives as JAK2 inhibitors was investigated by using multifaceted strategies including 3D-QSAR, molecular docking, Fingerprint analysis, MD simulations, and MM-PBSA calculations. A credible COMFA (q2 = 0.606 and r2 = 0.919) and COMSIA (q2 = 0.641 and r2 = 0.992) model was developed, where the internal and external validation revealed that the obtained 3D-QSAR models could be capable of predicting bioactivities of JAK2 inhibitors. The structural criteria provided by the contour maps of model were used to computationally develop more potent 100 new JAK2 inhibitors. Docking studies were conducted on the model data set and newly developed compounds (in-house library) to demonstrate their binding mechanism and highlight the key interacting residues within JAK2 active site. The selected docked complexes underwent MD simulation (100 ns), which contributed in the further study of the binding interactions. Binding free energy analyses (MMGB/PBSA) revealed that key residues such as Glu930, Leu932 (hinge region), Asp939 (solvent accessible region), Arg980, Asn981and Asp994 (catalytic site) have a significantly facilitate ligand-protein interactions through H-bonding and van der Waals interactions. The preliminary in-silico ADMET evaluation revealed encouraging results for all the modeled and in-house library compounds. The findings of this research have the potential to offer valuable recommendations for the advancement of novel, potent, and efficacious JAK2 inhibitors. Overall, this work has successfully employed a wide range of computer-based methodologies to understand the interaction dynamics between 2-amino-pyridine derivatives and the JAK2 enzyme, which is a crucial target in myeloproliferative disorders.Communicated by Ramaswamy H. Sarma.

Shear Bond Strength Of Etch And Rinse Adhesives To Dentin: Comparison Of Bond Strength After Acid And Papacarie Pre-Treatment.

BACKGROUND: Papacarie pre-treatment of dentin surface has been reported to exhibit good bond strength values between dentin and composites. Its desirable properties like high pH, sites specify and anti-inflammatory response makes it a future material in place acid etching pre-treatment. Acid etching may cause sensitivity and collapse of dentinal matrix. METHODS: This in-vitro study involved, 60 caries free extracted premolars, randomly divided into three groups. Control Group (Group A) No pre-treatment of dentin prior adhesive application. Experimental Group B acid etchant was applied before adhesive application. Experimental Group C Papacarie was used as a pre-treatment agent. All these specimens were tested for shear bond strength with the help of Universal Testing Machine. All the collected data was entered in SPSS version 20.0. ANOVA was used to determine the mean SBS (Shear Bond strength) values of control and experimental groups. RESULTS: The mean shear bond strength of material was 7.74±0.47 in group A, 17.80±1.43 in group B and 15.11±0.70 in group C. Group B showing better strength than other two groups. CONCLUSIONS: The study provides information about longevity of composite restorations and may help in extending the clinical usage of papacarie to avoid harmful effects of acid etching on dentin and pulpal tissue.

Dental Anxiety and Influencing Factors in Adults.

Dental anxiety is one of the most common conditions present amongst the masses globally. It is this fear that makes individuals avoid seeking dental treatment which results in a deteriorated oral health-related quality of life (OHRQoL). Discrepancies exist in the prevalence of dental anxiety based on gender, education levels, level of deprivation of a society and its socioeconomic status. In this study, a sample size of 522 respondents was collected. Kuppuswamy's socioeconomic status scale and modified dental anxiety scales were used to collect the necessary data. These data were analyzed by cross tabbing and chi-square test of significance was applied to assess the association between dental anxiety and other factors. Female gender was significantly associated with dental anxiety with p-value = 0.03. Higher education levels and dental anxiety also displayed significant associations with each other, with a p-value of 0.048. Seventy-six percent of the individuals of lower socioeconomic status were prone to be more dentally anxious. Dental anxiety was more significant in individuals with higher levels of education in our study. Respondents who were part of a lower socioeconomic class were also more prone to being anxious while receiving dental treatment. Knowing the factors that cause dental anxiety can help dentists effectively manage and treat their patients.

Demographic distribution of maxillofacial fractures in Ayub Teaching Hospital: 7-year review.

BACKGROUND: This retrospective study was carried out to determine the demographic distribution of Maxillofacial Fractures (MFF) in patients reported to Maxillofacial Surgical Unit, Ayub Teaching Hospital, Abbottabad from 2001 to 2007. METHODS: All the patients having a history of maxillofacial fractures were included according to age, gender distribution and risk factors. Isolated Nasal fractures, Naso-Orbito-Ethmiodal complex fractures and earthquake victims were excluded from this study. RESULTS: This study encompassed a total numbers of 952 patients. Males were 645 (67.8%) and females were 307 (32.2%) with male to female ratio 2.1:1. Most of the fractures occurred during third decade of life. The most common risk factor was Road Traffic Accident (RTA) n=70 (38.9%). Most of the fractures were occurred during the month of June, July and August. CONCLUSION: RTA is still the most common risk factor of maxillofacial fractures and is more common in male.