Iloperidone and Temozolomide Synergistically Inhibit Growth, Migration and Enhance Apoptosis in Glioblastoma Cells.

Glioblastoma (GBM) is a fatal astrocytic glioma with poor prognosis and treatment resistance. Repurposing potential FDA-approved drugs like anti-psychotics can address the concerns in a timely and cost-effective manner. Epidemiological studies have shown that patients with schizophrenic using anti-psychotics have a low incidence of GBM. Therefore, we aimed to investigate the therapeutic potential of atypical anti-psychotic Iloperidone (ILO) alone and in combination with Temozolomide (TMZ) against GBM. The study assessed the growth inhibitory effect of ILO, TMZ, and their combination (ILO + TMZ) on U-87MG and T-98G cell lines using an MTT assay. The drug interaction coefficient (CDI) was determined, and doses with synergistic effects were used for subsequent experiments, including migratory, invasion, and TUNEL assays. The expressions of DRD2, ß-catenin, Dvl2, Twist, and Slug were assessed by RTq-PCR, whereas the ß-catenin protein expression was also determined by immunocytochemistry. ILO (p < 0.05) and TMZ (p < 0.01) significantly inhibited the growth of U-87MG cells at all tested doses. The combination of 60 µM of both drugs showed synergistic activity with CDI < 1. The inhibition of migration and apoptosis was more pronounced in the case of combination treatment (p < 0.001). Inhibition of the invading cells was also found to be significant in ILO- and combination-treated groups (p < 0.001). ILO and combination treatment also significantly downregulated the expression of DRD2, while TMZ upregulated the expression (p < 0.001). The expressions of ß-catenin (p < 0.001), Dvl2 (p < 0.001), Twist (p < 0.001), and Slug (p < 0.001) were also significantly downregulated in all treatment groups as compared to the vehicle control. The data suggest that ILO possesses strong growth inhibitory activity, possibly due to its effect on DRD2 and ß-catenin expression and has the potential to be repurposed against GBM.

Anatomical variations of human sphenoid sinus in terms of volume and septation pattern in a subset of Pakistani population using computed tomographic images.

OBJECTIVE: To compare the sphenoid volume between the genders and to analyse variations in septal insertions on bony wall of optic nerve and internal carotid artery. METHODS: The prospective study was conducted from October 2020 to February 2021 at the Radiology Department of Dow University of Health Sciences, Karachi, and comprised paranasal sinus patients of either gender aged 20-60 without any bony deformity of sphenoid sinus who were analysed for sphenoid volume, number of septa and variable septal insertions using computed tomography of paranasal sinus. On the basis of septal insertions, the scans were categorised into Group 1 with no risky septal insertion, Group 2 with septal insertion on bony wall of optic nerve, Group 3 with septal insertion of internal carotid artery, and Group 4 with septal insertion on both optic nerve and internal carotid artery. Differences in sphenoid volume were analysed between males and females and among the four groups. Data was analysed using Graph Pad Prism 9. RESULTS: Of the 300 patients, 171(57%) were males and 129(43%) were females. The overall mean age was 39.28±10.9 years. Multiple septa were found in 208(69.3%) of the sinuses. There were 129(43.7%) patients in Group 1, 34(11.3%) in Group 2, 119(39%) in Group 3 and 18(6%) in Group 4. Significant difference was found between volume and gender as well as among the four groups (p<0.001). CONCLUSIONS: The sphenoid volume between the genders and the variations in septal insertions on bony wall of optic nerve and internal carotid artery were significantly different.

The Short-term Effects of Insulin, Metformin and Insulin-Metformin Combination on the Liver Morphology in High Fat Diet / Streptozotocin Induced Diabetic Albino Rats.

OBJECTIVE: To evaluate the histological effects of insulin, metformin and insulin-metformin combination on liver morphology in high fat diet (HFD) / Streptozotocin (STZ) induced diabetic albino rats. STUDY DESIGN: Experimental and comparative study. PLACE AND DURATION OF STUDY: Institute of Basic Medical Sciences (IBMS), Dow University of Health Sciences (DUHS), Ojha Campus, Karachi, from January to August 2012. METHODOLOGY: The study was conducted on 50 HFD/STZ induced diabetic albino wistar rats which were randomized into 5 groups. One of the groups was treated with insulin, one with metformin, and the other group with insulin-metformin combination for 4 weeks. One of the groups was left untreated. One group was control group. After the treatment period, the rats were sacrificed and livers were isolated, weighed, processed and stained to analyse the difference in hepatic morphology in each treated and untreated groups, then the results were compared with control rats. RESULTS: Statistically significant difference (p < 0.0001) was seen between the groups by using Kruskill Wallis Test. To further investigate the effectiveness of insulin, metformin and insulin-metformin combination, Mann-Whitney U-test was applied. Statistically significant difference was noticed when diabetic rats were given insulin-metformin combination (p < 0.0001). CONCLUSION: The combination therapy was observed to have better effects on liver morphology than insulin and metformin used separately.