Azhar Muhammad

Background: ATP-binding cassette Super-family G member 2 protein is an active ATPbinding cassette transporter with the potential to combat cancer stem cells.Objective: Due to the lack of potential ATP-binding cassette Super-family G member 2 inhibitors, we screened natural inhibitors, which could be a safe source to control multidrug resistance by blocking the regulation of ATP-binding cassette Super-family G member 2 protein.Methods: Three-dimensional structure of ATP-binding cassette Super-family G member 2 protein downloaded from the protein databank and chemical structures of 166 selected compounds of the training dataset were retrieved from PubChem. Drug-likeness and docking analysis was conducted to shortlist the dataset for pharmacophore generation. LigandScout 4.1.5 used for pharmacophorebased screening of Zbc library of ZINC database and Autodock Vina were utilized for molecular docking against the predicted active pocket of the target protein to evaluate the potential association of protein and ligands. The physiochemical properties of novel compounds were calculated by admetSAR respectively.Results: Through pharmacophore-based screening, ZINC4098704 (Rhein) was identified as a lead compound which demonstrates the least binding energy (-8.5) and the highest binding affinity with the target protein and showed optimal physiochemical profile. This compound is highly recommended for a laboratory test to confirm its activity as an ATP-binding cassette Super-family G member 2 inhibitors.Conclusion: Our computer-based study systematically selected natural lead compounds, which could be effective in inhibiting ATP-binding cassette Super-family G member 2 and may help reverse the effect of multidrug resistance to increase the effectiveness of chemotherapy in cancer treatment.

This manuscript was aimed to explore the hepato-protective effect of water extract of Veratrilla baillonii Franch. (Gentianaceae) (WVBF) on serious hepatic toxicity induced in mice treated with Aconitum brachypodum Diels (Ranunculaceae) at transcriptome level. The physiological and pathological symptoms were evaluated as the markers for hepato toxicity induced by A. brachypodum Diels (CFA) extracted compounds. Moreover, gene chip method was used to compare and investigate the gene expression level of WVBF on CFA induced-liver toxicity to identify the potential target of WVBF and CFA on liver. The results showed that WVBF had a significant detoxification effect on CFA-induced acute hepatic toxicity. There were 130 genes with lower expression and 124 genes expressed at higher rate in CFA treated group as compared with normal control group, while there are 67 genes down-regulated and 74 genes up-regulated in WVBF treated group in comparison with CFA treated group. WVBF could attenuate CFA-induced liver damage in mice through regulating oxidative stress, inflammatory injury and cell apoptosis/necrosis pathways. On the other hand, WVBF and CFA may have potential synergetic effects on the target genes of certain diseases such as inflammation, cancer and diabetes.

In recent years, researches focusing on PIWI-interacting RNAs (piRNAs) have increased rapidly. It has been revealed that piRNAs have strong association with a wide range of diseases; thus, it becomes very important to understand piRNAs’ role(s) in disease diagnosis, prognosis and assessment of treatment response. We searched more than 2500 articles using keywords, such as `PIWI-interacting RNAs’ and `piRNAs’, and further scrutinized the articles to collect piRNAs-disease association data. These data are highly complex and heterogeneous due to various types of piRNA idnetifiers (IDs) and different reference genome versions. We put considerable efforts into removing redundancy and anomalies and thus homogenized the data. Finally, we developed the piRDisease database, which incorporates experimentally supported data for piRNAs’ relationship with wide range of diseases. The piRDisease (piRDisease v1.0) is a novel, comprehensive and exclusive database resource, which provides 7939 manually curated associations of experimentally supported 4796 piRNAs involved in 28 diseases. piRDisease facilitates users by providing detailed information of the piRNA in respective disease, explored by experimental support, brief description, sequence and location information. Considering piRNAs’ role(s) in wide range of diseases, it is anticipated that huge amount of data would be produced in the near future. We thus offer a submitting page, on which users or researches can contribute in to update our piRDisease database.