ابن خرداذبہ اور ان كى كتاب المسالك والممالك: تاریخى وتنقیدى جائزہ

Ibn Khurdathba was a man with variable culture, he had an important role in the science of geography especially (knowing of the roads, locations of the cities, weather in addition to the news of general history and some arts like (music and singing )  The growth of Ibn Khurdathba in a family worked in the military field, close to the royal court has helped him to start his practical life early and allowed him also to contact with caliphs, ministers and writers in addition to occupying of the significant positions in the state, making it easier to get information from their original resources. Ibn Khurdathba has descended from Persian family lately entered into Islam۔ One of earliest geographical works of this period, his famous Kitab al- Masalik wa’l= Mamalik’. It gives a summary of the main trade routes of the Arab world and in addition provides description of such distant China, Korea and Japan. This article attempts his life and his “Al masalik wa al mamalik” book, varies sides.

Role of Hepatitis-C Virus Non Structural Proteins in the Induction of Insulin Resistance

Hepatitis C Virus is one of the lethal infections prevailing throughout the world. There are approximately 8.5 million individuals that are infected with this deadly virus in Pakistan. Hepatitis C virus is responsible for acute and chronic viral infection. Chronic hepatitis C virus infection causes persistent inflammation that leads to liver fibrosis, insulin resistance/type 2 diabetes mellitus, liver cirrhosis and finally hepatocellular carcinoma (HCC). There is strong evidence that insulin resistance has a major role in metabolic syndrome, and is a risk factor for increased liver fibrosis in patients with chronic hepatitis C virus infection. However the underlying mechanism of insulin resistance in chronic hepatitis C virus infection is not well known. The present study describes the molecular mechanism of HCV nonstructural protein 5A (NS5A) induced insulin resistance. In this study, we elucidated the molecular mechanism involved in HCV nonstructural protein 5A (NS5A) induced insulin resistance. In the present study human hepatoma cell line Huh 7.5 was transfected with HCV NS5A (Huh 7.5/NS5A) as well as HCV (JFH-1) genomic RNA was transfected into Huh 7.5 cell line (Huh 7.5/HCV) to discern the effect of HCV and HCV NS5A protein upon modulation of insulin signaling pathway. Here, we demonstrated that an increased serine phosphorylation of insulin receptor substrate-1 (pSer307) and Akt (pSer473) in Huh 7.5/HCV infected cells compared to mock infected cells. Interestingly, the Huh 7.5/NS5A cell line showed an increased serine phosphorylation of pSer307 IRS-1 and pSer473 Akt, compared to the mock transfected cells, which is a critical step defining the downstream insulin signaling pathway. Glycogen synthase kinase-3 (GSK-3), the downstream target of Akt, is known to favor gluconeogenesis. Our results revealed a diminished phosphorylation level of GSK-3 in Huh 7.5/NS5A expressing hepatoma cells compared to the mock transfected cells, thereby favoring gluconeogenesis. Forkhead transcription factor (FOX-01) which is another important downstream target of insulin signaling pathway, was shown to undergo reduced phosphorylation level (pSer 256) in Huh 7.5/NS5A expressing hepatoma cells compared to the mock transfected cells. Collectively, these findings suggest a molecular mechanism by which ectopic expression of Huh 7.5/NS5A modulates the insulin signaling pathway at post translational level. There are several gluconeogenic and lipogenic markers lying downstream to the insulin mediated signaling molecules (pSer307IRS-1, pSer473Akt, pSer256Fox-01 and GSK-3). In this study, we observed that Huh 7.5/HCV infected hepatoma cells as well as ectopic expression of Huh 7.5/NS5A leads to enhanced gluconeogenesis through up regulating the mRNA levels of gluconeogenic genes i.e. Phosphoenol pyruvate carboxy kinase (PEPCK) and Glucose-6-phosphatase (G6P) compared to their controls. In the similar way, an elevated mRNA level of Diacyl glycerol acyltransferase (DGAT), a key lipogenic marker, was also observed in Huh 7.5/HCV infected as well as Huh 7.5/NS5A expressing hepatoma cells compared to their controls. Based on these results, we deduce a mechanism through which HCV NS5A is potentially capable of modulating the entire insulin signaling pathway at mRNA and post-translational level thereby paving a way towards insulin resistance, a metabolic syndrome.