Farrukh Jamil

Evaluation of the safety of primary metabolites of cyadox: Acute and sub-chronic toxicology studies and genotoxicity assessment.

Cyadox (CYA) is a synthetic antimicrobial agent, belonging to quinoxaline (QdNO) family. Cy1 (bidesoxy cyadox), Cy2 (N4-desoxycyadox) and Cy10 (N1-desoxycyadox) are the primary metabolites of CYA. In our present study, an acute toxicity test, a sub-chronic toxicity test, and a battery of three genotoxicity tests were carried out according to standard protocols. The LD50 of the metabolites were above 5000xa0mg/kg b.w. The maximum tolerated dose (MTD) of Cy1 and Cy-M (mixture of Cy2 and Cy10) in rats, and the MTD of Cy1, Cy2 and Cy10 in mice were above 6000xa0mg/kg b.w./day. In subchronic study, rats were separately administered Cy1 and Cy-M at the dose levels of 0, 50, 150 and 2500xa0mg/kg diet for 90 days, with CYA (2500xa0mg/kg) as a control. Significant decreases in body weight and changes in clinical serum biochemistry were observed in the high-dose group of Cy1 and Cy-M, as well as CYA. Significant changes in relative weights of organs at 150 and 2500xa0mg/kg diet of Cy1 and CYA were noted. Additionally, the high-dose groups of Cy1, Cy-M and CYA showed pathological changes near the hepatic portal area. There was no evidence for genotoxic activity of any of the three metabolites in the bacterial reverse mutation test, mouse bone marrow micronucleus assay or an inxa0vitro assay for clastogenicity. Based on the subchronic study, the target organ of the primary metabolites was the liver, and the no-observed-adverse-effect level for Cy1 and Cy-M was 150xa0mg/kg diet.

Comparative Modeling, Molecular Docking, and Revealing of Potential Binding Pockets of RASSF2; a Candidate Cancer Gene

RASSF2, potential tumor suppressor gene, acts as a KRAS-specific effectors protein and may promote apoptosis and cell cycle arrest. It stabilizes STK3/MST2 by protecting it from proteasomal degradation. RASSF2 plays a significant role against the inhibition of cancer. MODELLER (9v15) and online servers (I-Tasser, SwissModel, 3D-JigSaw, ModWeb) were utilized to generate 3D structures of the RASSF2 based on homology modeling. A comparison between models predicted by MODELLER (9v15) and Web servers had been checked through utilized evaluation tools. The most potent model for RASSF2 was analyzed and selected for molecular docking studies. The binding pockets were revealed for binding studies through Site Hound. AutoDock Vina and AutoDock4 were utilized for molecular docking, and the attempt of this experiment was to identify the ligands for RASSF2. The selected compounds may act as regulators and regulate the normal activity of RASSF2. It was also analyzed and observed that the selected compounds showed least binding energy and high-affinity binding in predicted top binding domain. The determination of protein function is based on accurate identification of binding sites in protein structures. The binding site is known, and it may allow the ligand type and protein function to be determined by performing in silico and experimental procedures. The detection, comparison, and analysis of binding pockets are pivotal to drug discovery. It proposed that predicted structure is reliable for the structural insights and functional studies. The predicted binding pockets may lead to further analysis (drug discovery), used against cancer study.

Genetic variants in FGFR2 and TNRC9 genes are associated with breast cancer risk in Pakistani women

Single nucleotide polymorphisms (SNPs) lead to genetic differences in breast cancer (BC) susceptibility among women from different ethnicities. The present study aimed at investigating the involvement of SNPs of three genes, including fibroblast growth factor receptorxa02 (FGFR2), trinucleotide-repeat-containingxa09 (TNRC9) and mitogen-activated protein kinase kinase kinasexa01 (MAP3K1), as risk factors for the development of BC. A case‑control study (90‑100 cases; 90‑100 controls) was performed to evaluate five genetic variants of three genes, including FGFR2 (SNPs: rs1219648, rs2981582), TNRC9 (SNPs: rs8051542, rs3803662) and MAP3K1 (SNP: rs889312) as BC risk factors in Pakistani women. Significant associations were observed between BC risk and two SNPs of FGFR2 [rs2981582 (P=0.005), rs1219648 (P=9.08e‑006)] and one SNP of TNRC9 [rs3803662) (P=0.012)] in Pakistani women. On examining the different interactions of these SNPs with various clinicopathological characteristics, all three associated genetic variants, rs2981582 rs1219648 and rs3803662, exhibited a greater predisposition to sporadic, in comparison to familial, BC. Furthermore, there was an increased effect of BC risk between haplotype combinations of the two SNPs of FGFR2 (rs2981582 and rs1219648) in Pakistani women. The results of the present study suggest that variants of FGFR2 and TNRC9 may contribute to the genetic susceptibility of BC in Pakistani women.

Bio-Oil Upgrading by Catalytic Cracking Over Different Solid Catalysts

Fossil fuel crises along with global environmental issues, due to combustion of fossil fuel, lead to focus on biomass derived fuels. Bio-oil nowadays is seriously considered to be one of the favorable, renewable and alternative energy sources to replace fossil fuel and has become a significant energy carrier for transportation, industrial and commercial applications. In this study, bio-oil was upgraded by catalytic cracking in a fixed bed reactor in the presence of three different catalysts HY, H-mordenite and HZSM-5.All of the experimental runs were carried out at 500 °C, 0.3MPa and 15:1 oil to catalyst ratio. Catalysts characterization revealed that HZSM-5 with uniform pore and TPD analysis shows the presence of large number of acidic sites as compared to HY and H-mordenite. HZSM-5 proved its effectiveness in terms of deoxygenation and converting oxygenating compounds to hydrocarbons. The amount of hydrocarbons formed was 16.27 wt % OLP for HZSM-5, 15.16 wt% for HY and 14.954 wt % for H-mordenite. HZSM-5 possessed a strong acidity, uniform pore size and high activities which tended to permit the transformation of the oxygenated compounds present in the bio-oil to hydrocarbons. The upgraded bio-oil obtained posses improved physiochemical properties such pH which was increased from 2.21 to 3.56 while density was decreased upto 0.82 kg/m. The calorific value also increased upto 31.65 kJ/kg. The improved bio-oil by HZSM-5 catalyst can be considered as a potential for to be used as direct fuel.

In silico identification of novel Apolipoprotein E4 inhibitor for Alzheimer’s disease therapy

INTRODUCTIONnApolipoprotein E4 (ApoE) is a major genetic factor for developing Alzheimers disease (AD). It plays a vital role in brain to maintain a constant supply of neuronal lipids for rapid and dynamic membrane synthesis. Aggregation of beta amyloid plaques (Aβ) and neurofibrillary tangles in brain are responsible for onset of AD. The current study is designed to predict a drug against over activity of apoE4. 22 natural compounds (marine, microorganism and plant derivative) were used in current study.nnnMETHODSnThese compounds were used as inhibitors to target apoE4 protein activity. Moreover, six synthetic compounds were docked with target protein to compare and analyze the docking results with natural compounds. S-Allyl-L-Cysteine, Epicatechin Gallate and Fulvic acid showed highest binding affinity (-7.1, - 7 and -7 kcal /mol respectively). Analysis of the docked complex showed that Epicatechin Gallate bonded with Gln156 and Asp35. Furthermore, Fulvic Acid showed hydrogen bonding with Glu27. Among synthetic compound, Tideglusib had highest binding affinity with target protein but did not show hydrogen bonding with any amino acid residue. Moreover, a natural compound S-Allyl-LCysteine also showed highest binding affinity but did not show hydrogen bonding with any amino acid residue.nnnRESULTS AND CONCLUSIONnOur study highlighted Epicatechin Gallate as a potential lead compound on the basis of binding affinity and hydrogen bonding to inhibit the progression of AD.

Biodiesel production over a catalyst prepared from biomass-derived waste date pits

Highlights • Valorization of abundantly available waste date pits biomass.• Synthesized carbon catalyst possesses pore size >5 suitable for transesterification.• Green carbon catalyst found to be highly efficient and provided a biodiesel yield of 98.2%.• Produced biodiesel possessed acceptable fuel properties as per ASTM and EN standards.

Anaerobic membrane bioreactors for biohydrogen production: Recent developments, challenges and perspectives

Biohydrogen as one of the most appealing energy vector for the future represents attractive avenue in alternative energy research. Recently, variety of biohydrogen production pathways has been suggested to improve the key features of the process. Nevertheless, researches are still needed to overcome remaining barriers to practical applications such as low yields and production rates. Considering practicality aspects, this review emphasized on anaerobic membrane bioreactors (AnMBRs) for biological hydrogen production. Recent advances and emerging issues associated with biohydrogen generation in AnMBR technology are critically discussed. Several techniques are highlighted that are aimed at overcoming these barriers. Moreover, environmental and economical potentials along with future research perspectives are addressed to drive biohydrogen technology towards practicality and economical-feasibility.

In Silico Analyses of the Pseudogenes of Helicobacter pylori

Sr. No Sequence ID Protein sequence identity with functional parents LDF MFE 1 HP0039 (899692) Conjugal transfer protein [H. pylori] I:85;Q:98 4.01(4.10) -81(-249.90) 2 HP0041 (899153) Membrane protein [H. pylori] I:95;Q:94 0.52(5.19) -86.80(-323.40) 3 HP0052 (899240) Restriction endonuclease [H. pylori] I:93;Q:95 5.28(2.30) -291.20(-368.90) 4 HP0094 (899021) Alpha-1,2-fucosyltransferase [H. pylori] I:97;Q:100 6.5(U*) -141.10(-129.70) 5 HP0143 (899134) Citrate: succinate antiporter [H. pylori 26695] I:100;Q:100 4.96(4.96) -311(-311) 6 HP0205 (899036) ABC transporter ATPase [H. pylori] I:91;Q:99 6.51(4.81) -79.7(-709.50) 7 HP0254 (899058) hopX gene, [H. pylori] I:96;Q:100 1.44(U) -18.50(-383.31) 8 HP0343 (900317) Putative membrane protein [H. pylori] I:90;Q:89 2.52(7.41) -130.1(-258.60) 9 HP0369 (900281) Putative type II DNA modification enzyme/ Methyltransferase [H. pylori] I:100;Q:100 2.23(2.23) -33.50(-33.50)