Discovery of colchicine aryne cycloadduct as a potent molecule for the abrogation of epithelial to mesenchymal transition via modulating cell cycle regulatory CDK-2 and CDK-4 kinases in breast cancer cells.

In this study, we synthesized a new-generation library of colchicine derivatives via cycloaddition of colchicine utilizing position C-8 and C-12 diene system regioselectivity with aryne precursor to generate a small, focused library of derivatives. We assessed their anticancer activity against various cancer cell lines like MCF-7, MDA-MB-231, MDA-MB-453, and PC-3. Normal human embryonic kidney cell line HEK-293 was used to determine the toxicity. Among these derivatives, silicon-tethered compound B-4a demonstrated the highest potency against breast cancer cells. Subsequent mechanistic studies revealed that B-4a effectively modulates cell cycle regulatory kinases (CDK-2 and CDK-4) and their associated cyclins (cyclin-B1, cyclin-D1), inducing apoptosis. Additionally, B-4a displayed a noteworthy impact on tubulin polymerization, compared to positive control flavopiridol hydrochloride in a dose-dependent manner, and significantly disrupted the vimentin cytoskeleton, contributing to G1 arrest in breast cancer cells. Moreover, B-4a exhibited substantial anti-metastatic properties by inhibiting breast cancer cell migration and invasion. These effects are attributed to the down-regulation of major epithelial to mesenchymal transition (EMT) factors, including vimentin and Twist-1, and the upregulation of the epithelial marker E-cadherin in an apoptosis-dependent manner.

A comparative study to evaluate surface electromyographic correlations of mandibular implant-supported overdentures to conventional complete dentures in edentulous patients: An in vivo study.

Aim: The aim of this study was to compare the function and coordination of masticatory muscles for patients with two implant-supported mandibular overdenture (ISOD) with that of conventional complete dentures (CCD) using surface electromyography (sEMG). The objectives were to assess the muscle activity (efficiency) and clinical outcome after the transition of CCD patients to ISOD. Setting and Design: This was a crossover study. Materials and Methods: This clinical trial was conducted in the department of prosthodontics. A total of 15 patients (nine males and six females) were assessed using sEMG. In each patient, a total of four surfaces were examined above the following muscles - right and left masseter and right and left temporalis muscles. The electromyography readings were recorded to assess muscle activity during Clenching, cotton roll clenching, and chewing. The readings were recorded first for CCD and then for ISOD (after installing attachments). Statistical Analysis Used: Data analysis was done using independent t-test and one-way ANOVA. Results: Mean muscular activity of masseter during clenching, cotton roll clenching, and chewing for patients with ISOD (44.3 ± 11.2 µV, 41.1 ± 13.4 µV, and 45.2 ± 17.5 µV) was higher than CCD (26.0 ± 11.3 µV, 22.6 ± 9.7 µV, and 24.2 ± 9.5 µV). The mean muscular activity of temporalis during clenching, cotton roll clenching, and chewing was also higher with ISOD (47.9 ± 11.2 µV, 45.6 ± 11.9 µV, and 51.0 ± 14.4 µV) than CCD (31.0 ± 12.2 µV, 29.7 ± 15.3 µV and 31.9 ± 14.2 µV). No statistically significant result was found between masseter and temporalis muscle activity on both sides (P < 0.05), indicating symmetrical activity on both the sides. Conclusion: Two-ISODs prove to be a better and efficient treatment modality in rehabilitating edentulous patients as it enhances retention and also increases masticatory muscle activity and chewing efficiency.