Predominance of MGMT promoter methylation among Pakistani glioblastoma patients.

BACKGROUND: Glioblastoma multiforme (GBM), the most prevalent subgroup of neuroepithelial tumors, is characterized by dismal overall survival (OS). Several studies have linked O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation to OS in GBM patients. However, MGMT methylation frequencies vary geographically and across ethnicities, with limited data for South Asian populations, including Pakistan. This study aimed to analyze MGMT promoter methylation in Pakistani GBM patients. METHODS: Consecutive primary GBM patients diagnosed ≥ 18 years-of-age, with no prior chemotherapy or radiotherapy history, were retrospectively selected. DNA was isolated from formalin-fixed-paraffin-embedded tissues. MGMT promoter methylation was analyzed using methylation-specific PCR. Clinical, pathological, and treatment data were assessed using Fisher's exact/Chi-squared tests. OS was calculated using Kaplan-Meier analysis in SPSS 27.0.1. RESULTS: The study included 48 GBM patients, comprising 38 (79.2%) males and 10 (20.8%) females. The median diagnosis age was 49.5 years (range 18-70). MGMT methylation was observed in 87.5% (42/48) of all cases. Patients with MGMT methylation undergoing radiotherapy or radiotherapy plus chemotherapy exhibited significantly improved median OS of 7.2 months (95% CI, 3.7-10.7; P < 0.001) and 16.9 months (95% CI, 15.9-17.9; P < 0.001), respectively, compared to those undergoing surgical resection only (OS: 2.2 months, 95% CI, 0.8-3.6). CONCLUSION: This is the first comprehensive study highlighting a predominance of MGMT methylation in Pakistani GBM patients. Furthermore, our findings underscore the association of MGMT methylation with improved OS across diverse treatment modalities. Larger studies are imperative to validate our findings for better management of Pakistani GBM patients.

Population assessment of the Endangered Kashmir Gray Langur (Semnopithecus ajax, Pocock 1928) using the double-observer method.

Primates are among the most threatened taxa globally, therefore, there is a need to estimate and monitor their populations. Kashmir Gray Langur Semnopithecus ajax is an endangered species for which there is no population estimate. We used double-observer method to estimate its population size in the Kashmir region of North-Western Himalaya. We walked 1284 km across 31 survey blocks spanning all three divisions of Kashmir viz., North, Central, and South Kashmir, covering an area of 411 km2. We counted a minimum of 1367 individual langurs from 27 groups. The detection probability for observer 1 (0.719) and observer 2 (0.656) resulted in a population estimate of 1496 (95% confidence interval [CI] 1367-1899) across 30 groups (with a mean group size of 51), giving a density estimate of 3.64 (3.33-4.62) langurs/km². We found double-observer surveys to be suitable for the population estimation of langurs, and we make recommendations on how to effectively conduct primate surveys, especially in mountainous ecosystems. Our records extend the species distribution range beyond stated by the International Union for Conservation of Nature. Our findings also highlight that the Kashmir Himalaya is a stronghold of the species, where conservation efforts should focus.

Design, Synthesis, Docking Studies and Molecular Dynamics Simulation of New 1,3,5-Triazine Derivatives as Anticancer Agents Selectively Targeting Pancreatic Adenocarcinoma (Capan-1).

On the basis of remarkable anticancer profile of s-triazine nucleus, a new series of 2-methoxy-4-(3-morpholino-5-(arylamino)phenoxy)benzaldehyde derivatives 11 a-u was prepared and evaluated for in vitro antiproliferative activity against eight diverse human cancer cell lines (Capan-1, HCT-116, LN229, NCI-H460, DND-41, HL-60, K562 and Z138). Compounds 11 o, 11 r and 11 s were the most potent anticancer agents on pancreatic adenocarcinoma (Capan-1) cell line with IC50 value of 1.4, 5.1 and 5.3 µM, respectively, while compounds 11 f, 11 g, 11 k, 11 l and 11 n displayed selective activity against the pancreatic adenocarcinoma (Capan-1) cell line with IC50 values of 7.3-11.5 µM. These results indicate that derivative 11 o may serve as a promising lead compound for the ongoing development of novel antiproliferative agents. The docking studies were conducted to predict the interactions of derivative 11 o with putative protein targets in pancreatic adenocarcinoma (Capan-1) cell line, specifically the prenyl-binding protein PDEδ. Furthermore, the analysis of the molecular dynamics simulation results demonstrated that complex 11 o promoted a higher stability to the prenyl-binding protein PDEδ.

Genetic diversity analysis of Bemisia tabaci populations in Pakistan using RAPD markers

Background: The Bemisia tabaci is one of the most devastating pests of agricultural crops and ornamental plants worldwide. The genetic diversity and biotype status of the Bemisia tabaci in Pakistan was assessed by using random amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR). A total 80 samples of B. tabaci collected from 14 districts of the Punjab province and 7 districts of the Sindh province were included. Results: All 10 primers screened in this study generated 151 scorable amplification products, of which 117 or 77 percent were polymorphic. Pairwise Nei and Li’s similarity had ranged from 0.25 to 0.88 among all individuals analyzed. Based on Nei and Li’s similarity coefficients Bemisia populations were grouped into 3 main clusters and clearly distinguished the non B biotype from the B biotype. Conclusion: The level of similarity among populations of same biotypes was high whereas between populations of non B and B biotypes appeared to be less closely related. This analysis showed that non B biotype is prevalent in both provinces however B biotype is restricted to few locations in Sindh. This monitoring of the spread of B. tabaci in Pakistan will assist in the establishment of appropriate management strategies.