Hepatitis C virus genotypes circulating in district Swat of Khyber Pakhtoonkhaw, Pakistan

Hepatitis C virus (HCV) is the leading cause of chronic hepatitis worldwide and its subtypes/genotypes are clinically important for clinical management and vaccine development. The present study describes frequency distribution of different HCV genotypes and their treatment status in HCV RNA positive patients from district Swat. A total of 185 HCV infected sera were analyzed by molecular genotyping assay. The most prevalent genotype was 3a (34.1%), followed by 2a (8.1%), 3b (7%) and 1a (5.4%). The samples found untypable by the present method of genotypes was 37.8% while, patients with mixed genotype infections were 7.6%. More than 80% of untypable cases were from those HCV patients who had received interferon plus ribavirin standard therapy in the past and either were non-responders and were relapsed thereafter or were under treatment. In conclusion, genotype 3a is the most prevalent HCV genotype in the region. A high prevalence rate of untypable genotypes is present in treated patients that need further investigation for the successful genotyping by developing new assays or using viral sequencing method

The mutational analysis of mitochondrial DNA in maternal inheritance of polycystic ovarian syndrome

IntroductionPolycystic Ovarian Syndrome (PCOS) is a globally prevalent condition that leads to infertility in women. While environmental factors contribute to PCOS, maternal genetics also play a significant role. Currently, there is no definitive test for identifying predisposition to PCOS. Hence, our objective is to discover novel maternal genetic risk factors for PCOS by investigating the genomes of patients from Pakistan.MethodsWe utilized Next-Generation Sequencing (NGS) to sequence the complete mitochondrial DNA of three PCOS patients. Subsequently, we employed MitoTIP (Mitochondrial tRNA Informatics Predictor) and PON-mt-tRNA tools to identify variations in the mitochondrial DNA. Our analysis focused on the genes MT-RNR1, MT-RNR2, MT-ATP6, MT-TL2, and MT-CYTB, which displayed common variations in all three genomes. Additionally, we observed individual variations. The D-loop region exhibited the highest frequency of mutations, followed by the non-coding regions of RNR1 and RNR2 genes. Moreover, we detected frameshift mutations in the mitochondrially encoded NADH Dehydrogenase 2 (MT-ND2) and mitochondrially encoded NADH Dehydrogenase 5 (ND5) genes within individual genomes.ResultsOur analysis unveiled six regions with common variations in the mitochondrial DNA of all three PCOS patients. Notably, the MT-RNR1, MT-RNR2, MT-ATP6, MT-TL2, and MT-CYTB genes exhibited these variations. Additionally, we identified individual variations in the mitochondrial DNA. The D-loop region displayed the highest mutation frequency, followed by the non-coding regions of RNR1 and RNR2 genes. Furthermore, frameshift mutations were detected in the MT-ND2 and ND5 genes within individual genomes.ConclusionThrough our study, we have identified variations in mitochondrial DNA that may be associated with the development of PCOS and have the potential to serve as predisposition tests. Our findings highlight the presence of novel mutations in the MT-RNR1, MT-RNR2, MT-ATP6, MT-TL2, and MT-CYTB genes, as well as frameshift mutations in the MT-ND2 and ND5 genes. Pathogenicity analysis indicated that most variants were likely to result in benign cysts. However, the frameshift mutations in the ND2 gene were associated with a high risk of complications and pathogenicity in PCOS. This is the first report identifying these mutations and their association with PCOS, contributing to our understanding of the genetic factors underlying the condition

Synthesis, characterization and biological evaluation of some new oxino bis-pyrazole derivatives

Novel oxino bis-pyrazoles were obtained by two step reactions of 3-methyl-1-phenyl pyrazoline-5-one, cyanoacetamide and aryl- or alkylaldehydes, in the presence of catalytic amounts of triethylamine and ethanol as a solvent. All the synthesized compounds were evaluated for their inhibitory activities against butyrylcholinesterase (BChE) and bovine a-chymotrypsin. Two compounds, 8 and 9 were found to be good inhibitors of enzyme BChE with IC50 values of 52.74 ± 0.006 and 51.85 ± 0.005 μM, respectively