Comprehensive analysis of root canal morphology in maxillary premolars among the Pakistani subpopulation: a CBCT-based study.

BACKGROUND: Understanding the root canal morphology is essential for the success of root canal treatment. Therefore, this study aimed to evaluate and analyze the root canal configuration of maxillary premolars using Cone Beam Computed Tomography in the Pakistani subpopulation. METHOD: This cross-sectional study utilized CBCT scans from two distinct centres: Aga Khan University in Karachi and Jinnah MRI and Body Scans in Lahore. The CBCT images were visualized using GALAXIS version 1.9 (SICAT GmbH and Co. KG, Bonn, Germany), integrated within the Sirona Dental System (D-64625 Bensheim, Germany). The scanning parameters were standardized at 85 kV, 7 mA, with a 15-s exposure time and a voxel size of 0.16 mm. A total of 707 CBCT scans were collected, encompassing 2180 maxillary premolars. Root canal configurations were classified based on (Ahmed et al. Int Endod J. 2017;50(8):761-70). Statistical analyses were performed using SPSS version 26, employing the Chi-square test with a significance level set at p < 0.05. RESULTS: The distribution of root canal morphologies varied significantly with age and gender. Among maxillary premolars, 50% exhibited the typical configuration of 2MPMB1 L1 (two roots, single canal in each buccal and lingual root), while 26% of maxillary right second premolars displayed 1MPM1 (one root, one canal). Overall, 1MPM1 accounted for 27.4% of the total cases in the second premolars. There was no statistically significant relationship between age and root canal distribution in either first premolars (p = 0.338) or second premolars (p = 0.833). Regarding gender, a significant difference was observed in the distribution of right maxillary 1st premolars (p = 0.022*), with a higher prevalence among females. CONCLUSION: This study offers significant insights into the anatomical variations of root canals in maxillary premolars across diverse regional subpopulations in Pakistan. While specific root canal configurations were prevalent, the findings indicate no statistically significant correlation between age and root canal morphology in maxillary premolars. However, a notable gender disparity was observed in the distribution of the right maxillary first premolars.

Insights into molecular docking and dynamics to reveal therapeutic potential of natural compounds against P53 protein.

P53 is eminent tumour suppressor protein that plays a prominent role in cell cycle arrest, DNA repair, senescence, differentiation and initiation of apoptosis. P53 is an attractive drug target and the high toxicity of some cancer chemotherapy drugs increase the demand for new anti-cancer drugs from natural products. In this current scenario, identification of promising anticancer compounds from natural sources by repurposing approach is still relevant for the early prevention and effective management of cancer. In present study, we docked natural compounds like podophyllotoxin, quercetin and rutin along standard drugs (MG-132 and Bay 61-3606) against p53 protein. ADME/T analysis predicted toxicity of phytochemicals and drugs. In silico docking analysis of podophyllotoxin, quercetin and rutin gave HDOCK docking scores of -187.87, -148. 97 and -143.85, whereas control drugs MG-132 and Bay 61-3606 showed docking scores of -159.59 and -140.71 against p53 respectively. AutoDock analysis of rutin and MG-132 showed highest binding affinity scores of -7.3 and -6.8 kcal/mol against p53. Molecular dynamic simulation for p53 protein displayed stable conformation and convergence. In this study, P53-rutin complex showed free binding energy score of 11.84 kcal/mol and P53-MG-132 complex reported free energy score of 16.3 kcal/mol. Protein contacts atlas gives non-covalent contacts framework by exploring interfaces of individual subunits and protein-ligand interactions. STRING tool predicts physical and functional interactions between proteins. The results of this study revealed that rutin and MG-132 could be promising inhibitors against targeted p53 protein and this could prove detrimental for molecular therapeutics and drug-designing strategies.Communicated by Ramaswamy H. Sarma.

Role of sonic hedgehog ligand in gastric cancer therapeutics.

Purpose: The abnormal activation of the sonic hedgehog (SHH) signaling pathway is responsible for the progression of several types of cancers including Gastric Cancer (GC). SHH has been associated with the activation of different signaling pathways. Therefore, in this study, we investigated messenger RNA (mRNA) and protein expression of SHH in gastric malignancies and possible correlation with various clinicopathological parameters. Materials and Methods: A total of 53 surgically resected tumors and adjacent histologically normal tissues from GC patients were investigated in study subjects. A quantitative real-time polymerase chain reaction and immunohistochemistry methods were used for expression analysis of SHH. Results: At mRNA level, SHH was overexpressed in 60% (27/45) of GC cases as compared to their adjacent normal tissues. SHH immunohistochemical analysis revealed abundant cytoplasmic localization and overexpression in 43.39% (23/53) of GC tissues. SHH overexpression was not associated with any of the clinicopathological parameters. Conclusion: Our results showed that SHH is dysregulated in GC and might be considered as a biomarker for GC progression and can be used as a target in cancer therapeutics.

Connective tissue growth factor expression hints at aggressive nature of colorectal cancer.

BACKGROUND: Connective tissue growth factor (CTGF) is a mediator of transforming growth factor-beta signaling and plays a key role in connective tissue remodeling, inflammatory processes and fibrosis in various illnesses including cancer. AIM: To investigate the role of CTGF in colorectal cancer (CRC) progression and to compare the CTGF expression with different clinicopathological parameters. METHODS: Real-time polymerase chain reaction, immunohistochemistry and Western blotting was performed to evaluate the CTGF expression and the results were statistically analyzed against the clinicopathological variables of patient data using STATA software version 16. RESULTS: CTGF expression levels in tumor specimens were significantly higher than their paired normal specimens. The higher protein expression levels showed a significant association with smoking, staging, tumor grade, invasion depth, necrosis of tumor tissue, and both lymphovascular and perineural invasion. As per the cox regression model and classification tree analysis, tumor-node-metastasis stage and perineural invasion were important predictors for CTGF expression and prognosis of CRC patients. Survival analysis indicated that CTGF overexpression was associated with poorer overall and disease-free survival. CONCLUSION: Expression of CTGF was increased in CRC and was linked with poor overall and disease-free survival of CRC patients. These findings support prior observations and thus CTGF may be a possible prognostic marker in CRC.

TEAD4 nuclear localization and regulation by miR-4269 and miR-1343-3p in colorectal carcinoma.

BACKGROUND AND AIMS: TEAD4 transcription factor belonging to TEAD-family, is a key downstream element of the Hippo Signalling pathway and is very important for YAPinduced tumor progression. YAP-TEAD interaction is required to promote tumor progression and metastasis in various cancers. This study aims to investigate the role of TEAD4 in CRC progression and to compare the TEAD4 expression with different clinicopathological parameters of the study population. We also aim to explore the expression pattern of miR-4269 and miR-1343-3p and their functional role in TEAD4 mediated CRC progression. Furthermore, we intend to evaluate the prognostic significance of TEAD4, miR-4269, and miR-1343-3p in colorectal carcinoma. METHODS: Real-time PCR, Immunohistochemical Staining, and Western Blotting were performed on 71 human CRC tissue specimens and their adjacent normal tissues to evaluate the TEAD4 expression and the results were statistically analyzed against the clinicopathological variables of patient data and also with survival data using STATA software. miRNA expression was analyzed by quantitative real-time PCR. RESULTS: TEAD4 expression levels in tumor specimens were significantly higher than their paired normal specimens. The higher protein expression levels showed a significant association with TNM stage, Duke Stage, tumor grade, invasion depth, node status, necrosis of tumor tissue, lymphovascular and perineural invasion. As per the cox-regression model and classification tree analysis, TNM stage and perineural invasion were important predictors for TEAD4 expression and prognosis of CRC patients. Survival analysis indicated that TEAD4 overexpression was associated with poorer overall and disease-free survival. miR-4269 and miR-1343-3p were downregulated in CRC tumors and showed a negative correlation with TEAD4. The nuclear overexpressed TEAD4 and downregulated miR-4269 and miR-1343-3p evaluated for the first time in CRC, are believed to serve as important prognostic markers in CRC. CONCLUSION: Expression of TEAD4 was increased in CRC and was negatively regulated by miR-4269 and miR-1343-3p. The overexpression of TEAD4 is linked with poor overall and disease-free survival of CRC patients. These findings support prior observations and thus TEAD4 may be a possible prognostic marker in CRC.