BackgroundLung cancer is a leading cause of cancer-related death worldwide and is the most commonly diagnosed cancer. Like other cancers, it is a complex and highly heterogeneous disease involving multiple signaling pathways. Identifying potential therapeutic targets is critical for the development of effective treatment strategies.MethodsWe used a systems biology approach to identify potential key regulatory factors in smoking-induced lung cancer. We first identified genes that were differentially expressed between smokers with normal lungs and those with cancerous lungs, then integrated these differentially expressed genes (DEGs) with data from a protein-protein interaction database to build a network model with functional modules for pathway analysis. We also carried out a gene set enrichment analysis of DEG lists using the Kinase Enrichment Analysis (KEA), Protein-Protein Interaction (PPI) hubs, and KEGG (Kyoto Encyclopedia of Genes and Genomes) databases.ResultsTwelve transcription factors were identified as having potential significance in lung cancer (CREB1, NUCKS1, HOXB4, MYCN, MYC, PHF8, TRIM28, WT1, CUX1, CRX, GABP, and TCF3); three of these (CRX, GABP, and TCF) have not been previously implicated in lung carcinogenesis. In addition, 11 kinases were found to be potentially related to lung cancer (MAPK1, IGF1R, RPS6KA1, ATR, MAPK14, MAPK3, MAPK4, MAPK8, PRKCZ, and INSR, and PRKAA1). However, PRKAA1 is reported here for the first time. MEPCE, CDK1, PRKCA, COPS5, GSK3B, BRCA1, EP300, and PIN1 were identified as potential hubs in lung cancer-associated signaling. In addition, we found 18 pathways that were potentially related to lung carcinogenesis, of which 12 (mitogen-activated protein kinase, gonadotropin-releasing hormone, Toll-like receptor, ErbB, and insulin signaling; purine and ether lipid metabolism; adherens junctions; regulation of autophagy; snare interactions in vesicular transport; and cell cycle) have been previously identified.ConclusionOur systems-based approach identified potential key molecules in lung carcinogenesis and provides a basis for investigations of tumor development as well as novel drug targets for lung cancer treatment.

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Keywords:River Nile, Rosetta Branch, water quality, heavy metals, Orechromus niloticus, Inter-simple sequence repeats (ISSR)The present study aims to evaluate the water quality of two locations in Rosetta Branch of River Nile and its histopathological and genetic adverse effects on Nile tilapia (Oreochromis niloticus). Water and fish samples were collected from up and downstream of El-Rahawy Drain discharge point (location I and II, respectively) during the summer and winter seasons. The water quality, liver histopathology and DNA alteration of fish was examined. ISSR-PCR technique was used to assess the genetic variation of fish samples from these locations. The water quality parameters ( BOD, COD,……)were increased at location II compared with location I in addition to depletion in dissolved oxygen. Moreover, the fish samples collected from location II showed severe histological and molecular alterations than those collected from location I. It is recommended that the government must increase the awareness of people around the River Nile, and improve the environmental management to reduce the risks of polluted water and consuming the fish exposed to this water on human health. Hashem et al. , 2020 20Impact of the water quality of River Nile on Oreochromis niloticus _________________________________________________________________________________ 21

Hepatitis C is a major healthcare problem that launched the quest and the interest of scientists to search for solutions that alleviate its risks. New groups of drugs are developed and repurposed for this reason. One of the drugs that recently repurposed to be used as an anti-HCV drug is Nitazoxanide (NTZ). NTZ is mainly a thiazolide antiparasitic drug that is mainly used for the treatment of cryptosporidiosis and giardiasis. Tizoxanide (TIZ), which is the active metabolite of NTZ, was recently reported to be active against some viruses including hepatitis C virus (HCV). The anti-HCV mode of action of Nitazoxanide is the overproduction of the hyperphosphorylated HCV non-structural protein 5 A (NS5A). However, the exact mechanism of action is not so clear. Some previous works suggested one member of the CMGC Serine/Threonine protein kinase family to be the primary cellular target of NTZ. A more recent work revealed that NS5A is a direct substrate of casein kinase I a (CKIa). However, no direct effect of NTZ or TIZ was reported on CKIa in enzymatic assays. In this work, starting with the chemical structure of NTZ and TIZ, some in-silico approaches were applied to hypothesize the human primary cellular target for NTZ. Accordingly, glycogen synthase kinase 3b (GSK3b), a member of CMGC Serine/Threonine protein kinase family, was retrieved as a proposed target of NTZ that is likely mediating its anti-HCV effect.