Experimental investigation and molecular simulations of quinone related compounds as COX/LOX inhibitors.

Quinone-containing compounds have risen as promising anti-inflammatory targets; however, very little research has been directed to investigate their potentials. Accordingly, the current study aimed to design and synthesize group of quinones bearing different substituents to investigate the effect of these functionalities on the anti-inflammatory activities of this important scaffold. The choice of these substituents was carefully done, varying from a directly attached heterocyclic ring to different aromatic moieties linked through a nitrogen spacer.

Structure-guided approach on the role of substitution on amide-linked bipyrazoles and its effect on their anti-inflammatory activity.

A structure-guided modelling approach using COX-2 as a template was used to investigate the effect of replacing the chloro atom located at the chlorophenyl ring of amide-linked bipyrazole moieties, aiming at attaining better anti-inflammatory effect with a good safety profile. Bromo, fluoro, nitro, and methyl groups were revealed to be ideal candidates. Consequently, new bipyrazole derivatives were synthesised.

Studies on isolation and inhibitory effect on food-borne pathogens from raw milk in Egypt by natural oils.

This study sheds the light on the presence of (some) food-borne pathogens in raw market milk in Mansoura city, (Egypt) using several techniques for isolation and identification including serology and PCR. It determines, further, the susceptibility of the isolated pathogens to some antimicrobial agents and natural oils, including watercress, basil, parsley, and hot green pepper oils. From 100 milk samples, 22 Escherichia coli isolates harboured stx1, stx2 and/or eae genes.

Quorum sensing inhibitory activity of sub-inhibitory concentrations of β-lactams.

Introduction: The virulence factors of are under the control of quorum sensing (QS) signals. Hence, interference with QS prevents its pathogenesis.

Objective: The aim of the present research is to assess the influence of some β-lactam antibiotics on cell communication and the release of different virulence factors.

Multidrug-resistant ESBL-producing Enterobacteriaceae and associated risk factors in community infants in Lebanon.

Introduction: Extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) infections are a growing threat to children, and the treatment of these infections becomes more and more challenging. A huge reservoir for ESBLs in the community is the fecal flora of children. This study investigates the rectal colonization, associated risk factors, antimicrobial susceptibility, and molecular characterization of ESBL-PE in Lebanese community infants.

Nephroprotective role of dipyridamole in diabetic nephropathy: Effect on inflammation and apoptosis.

Aims: Inflammation plays significant roles in developing diabetic nephropathy (DN). Adenosine, natural purine nucleoside, acts as potent endogenous anti-inflammatory agent. Extracellular adenosine usually disappears quickly due to rapid uptake into adjacent cells.

Hepatoprotective and anti-tumor effects of targeting MMP-9 in hepatocellular carcinoma and its relation to vascular invasion markers.

The current study aims to evaluate the hepatoprotective and antitumor efficacy of doxycycline, as an matrix metalloproteases-9 (MMP-9) inhibitor, in an in vivo model of hepatocellular carcinoma (HCC). HCC was induced experimentally by thiocetamide (200 mg/kg) in rats that were treated with doxycycline (5 mg/kg for 16 weeks). Tumor severity was evaluated by measuring α-fetoprotein (AFP) levels, histopathologically by investigating liver sections stained with hematoxylin/eosin and assessing the survival rate.

Evaluation of antiglypican-3 therapy as a promising target for amelioration of hepatic tissue damage in hepatocellular carcinoma.

In Egypt, hepatocellular carcinoma (HCC) was predicted to continue to rise over the next few decades causing a national problem. Meanwhile, glypican-3 (GPC3), a highly expressed glypican, has emerged as a potential target for HCC immunotherapy. Therefore, we aimed to identify the impact of blocking GPC3 on liver damage in HCC as well as a possible mechanism.

Aspirin is an efficient inhibitor of quorum sensing, virulence and toxins in Pseudomonas aeruginosa.

Quorum sensing (QS) plays a vital role in regulation of virulence factors and toxins in Pseudomonas aeruginosa, which can cause serious human infections. Therefore, the QS system in P. aeruginosa may be an important target for pharmacological intervention.

Suramin inhibits hepatic tissue damage in hepatocellular carcinoma through deactivation of heparanase enzyme.

Hepatocellular carcinoma (HCC) is resistant to conventional chemotherapy, and is rarely amenable to radiotherapy. Heparanase, enzyme attacks heparan sulfate proteoglycans (HSPGs), is preferentially expressed in human tumors and its overexpression in low-metastatic tumor confers a highly invasive phenotype in experimental animals. Meanwhile, high doses of suramin dramatically increase tissue glycosaminoglycans due, in part, to inhibition of heparanase enzymes.

Reno-protective effect of NECA in diabetic nephropathy: implication of IL-18 and ICAM-1.

Diabetic nephropathy (DN) remains the most common cause of end-stage renal disease. Although, adenosine acts as a local modulator with a cytoprotective function, extracellular adenosine usually disappears quickly due to a rapid uptake into adjacent cells. Therefore, we investigated the effect of 5'-(N-ethylcarboxamido)-adenosine (NECA), a stable, nonselective adenosine receptor agonist, on diabetes-induced increases in inflammatory cytokines and adhesion molecules.

Intrinsic restriction activity by apolipoprotein B mRNA editing enzyme APOBEC1 against the mobility of autonomous retrotransposons.

The ability of mammalian cytidine deaminases encoded by the APOBEC3 (A3) genes to restrict a broad number of endogenous retroelements and exogenous retroviruses, including murine leukemia virus and human immunodeficiency virus (HIV)-1, is now well established. The RNA editing family member apolipoprotein B (apo B)-editing catalytic subunit 1 (APOBEC1; A1) from a variety of mammalian species, a protein involved in lipid transport and which mediates C-U deamination of mRNA for apo B, has also been shown to modify a range of exogenous retroviruses, but its activity against endogenous retroelements remains unclear. Here, we show in cell culture-based retrotransposition assays that A1 family proteins from multiple mammalian species can also reduce the mobility and infectivity potential of LINE-1 (long interspersed nucleotide sequence-1, L1) and long-terminal repeats (LTRs) retrotransposons (or endogenous retroviruses), such as murine intracisternal A-particle (IAP) and MusD sequences.

Vipirinin, a coumarin-based HIV-1 Vpr inhibitor, interacts with a hydrophobic region of VPR.

The human immunodeficiency virus 1 (HIV-1) viral protein R (Vpr) is an accessory protein that has been shown to have multiple roles in HIV-1 pathogenesis. By screening chemical libraries in the RIKEN Natural Products Depository, we identified a 3-phenyl coumarin-based compound that inhibited the cell cycle arrest activity of Vpr in yeast and Vpr-dependent viral infection of human macrophages. We determined its minimal pharmacophore through a structure-activity relationship study and produced more potent derivatives.

Real-time nucleic acid sequence-based amplification assay for detection of hepatitis A virus.

A nucleic acid sequence-based amplification (NASBA) assay in combination with a molecular beacon was developed for the real-time detection and quantification of hepatitis A virus (HAV). A 202-bp, highly conserved 5' noncoding region of HAV was targeted. The sensitivity of the real-time NASBA assay was tested with 10-fold dilutions of viral RNA, and a detection limit of 1 PFU was obtained.

Combined immunomagnetic separation-molecular beacon-reverse transcription-PCR assay for detection of hepatitis A virus from environmental samples.

In this study, a molecular-beacon-based real-time reverse transcription (RT)-PCR assay was developed to detect the presence of hepatitis A virus (HAV) in environmental samples. A 125-bp, highly conserved 5' noncoding region of HAV was targeted. The sensitivity of the real-time RT-PCR assay was tested with 10-fold dilutions of viral RNA, and a detection limit of 1 PFU was obtained.