Sanaa K. Bardaweel

Complementary and alternative medicine utilization by a sample of infertile couples in Jordan for infertility treatment: clinics-based survey

BackgroundAlthough there is little information available to quantify the use of complementary and alternative medicine (CAM), growing evidence suggests that CAM prevalence among patients seeking infertility treatment is increasing worldwide. There are many products available on the market and many infertile patients demand information about CAM from their health care providers. This paper investigates the prevalence of CAM use among infertile couples in Jordan. Additionally, trends and factors contributing to CAM use for infertility treatment among these couples have been evaluated.MethodsA face-to-face questionnaire inquiring demographic information, use of CAM for medical conditions, in general, and types of CAM used for infertility treatment, in specific, was completed by one thousand twenty one infertile patients attending at two types of facilities; in vitro Fertilization (IVF) centers at both public and private hospitals and infertility private clinics. Both types of facilities were distributed in different areas of Amman, the capital city of Jordan. The study was conducted between May and August 2012.ResultsOur results show that CAM therapies for infertility treatment were encountered in 44.7% of the study sample. The vast majority of CAM users were females. The most commonly used CAM therapies were herbs and spiritual healing. A clear correlation between the use of CAM for infertility versus the use of CAM for other chronic medical conditions has been found.ConclusionsThe prevalence of CAM use for infertility treatment in Jordan is relatively high, particularly among young females, well educated and with a low income, in consistence with the studies reported elsewhere. Herbs and spiritual healing are widely used among patients in adjunct to conventional medical interventions. As CAM use is prevalent among patients, there is a clear need for health providers to become more aware of this phenomenon and for further research in this field.

Synthesis of Novel 2,5-Disubstituted-1,3,4-thiadiazoles Clubbed 1,2,4-Triazole, 1,3,4-Thiadiazole, 1,3,4-Oxadiazole and/or Schiff Base as Potential Antimicrobial and Antiproliferative Agents

In the present study, a new series of 2,5-disubstituted-1,3,4-thiadiazole tethered 1,2,4-triazole, 1,3,4-thiadiazole, 1,3,4-oxadiazole and Schiff base derivatives were synthesized and characterized by IR, 1H-NMR, 13C-NMR, MS and elemental analyses. All compounds were screened for their antibacterial, antifungal and antiproliferative activity. Some of the synthesized derivatives have displayed promising biological activity.

Probing the Impact of the EchinT C-Terminal Domain on Structure and Catalysis

Histidine triad nucleotide binding protein (Hint) is considered as the ancestor of the histidine triad protein superfamily and is highly conserved from bacteria to humans. Prokaryote genomes, including a wide array of both Gram-negative bacteria and Gram-positive bacteria, typically encode one Hint gene. The cellular function of Hint and the rationale for its evolutionary conservation in bacteria have remained a mystery. Despite its ubiquity and high sequence similarity to eukaryote Hint1 [Escherichia coli Hint (echinT) is 48% identical with human Hint1], prokaryote Hint has been reported in only a few studies. Here we report the first conformational information on the full-length N-terminal and C-terminal residues of Hint from the E. coli complex with GMP. Structural analysis of the echinT-GMP complex reveals that it crystallizes in the monoclinic space group P2(1) with four homodimers in the asymmetric unit. Analysis of electron density for both the N-terminal residues and the C-terminal residues of the echinT-GMP complex indicates that the loops in some monomers can adopt more than one conformation. The observation of conformational flexibility in terminal loop regions could explain the presence of multiple homodimers in the asymmetric unit of this structure. To explore the impact of the echinT C-terminus on protein structure and catalysis, we conducted a series of catalytic radiolabeling and kinetic experiments on the C-terminal deletion mutants of echinT. In this study, we show that sequential deletion of the C-terminus likely has no effect on homodimerization and a modest effect on the secondary structure of echinT. However, we observed a significant impact on the folding structure, as reflected by a significant lowering of the T(m) value. Kinetic analysis reveals that the C-terminal deletion mutants are within an order of magnitude less efficient in catalysis compared to wild type, while the overall kinetic mechanism that proceeds through a fast step, followed by a rate-limiting hydrolysis step, was conserved. Nevertheless, the ability of the C-terminal deletion mutants to hydrolyze lysyl-AMP generated by LysU was greatly impaired. Taken together, our results highlight the emerging role of the C-terminus in governing the catalytic function of Hints.

Olive Oil‐derived Oleocanthal as Potent Inhibitor of Mammalian Target of Rapamycin: Biological Evaluation and Molecular Modeling Studies

The established anticancer and neuroprotective properties of oleocanthal combined with the reported role of mammalian target of rapamycin (mTOR) in cancer and Alzheimers disease development encouraged us to examine the possibility that oleocanthal inhibits mTOR. To validate this hypothesis, we docked oleocanthal into the adenosine triphosphate binding pocket of a close mTOR protein homologue, namely, PI3K‐γ. Apparently, oleocanthal shared nine out of ten critical binding interactions with a potent dual PIK3‐γ/mTOR natural inhibitor. Subsequent experimental validation indicated that oleocanthal indeed inhibited the enzymatic activity of mTOR with an IC50 value of 708 nM. Oleocanthal inhibits the growth of several breast cancer cell lines at low micromolar concentration in a dose‐dependent manner. Oleocanthal treatment caused a marked downregulation of phosphorylated mTOR in metastatic breast cancer cell line (MDA‐MB‐231). These results strongly indicate that mTOR inhibition is at least one of the factors of the reported anticancer and neuroprotective properties of oleocanthal. Copyright

D-Serine in neurobiology: CNS neurotransmission and neuromodulation.

Homochirality is fundamental for life. L-Amino acids are exclusively used as substrates for the polymerization and formation of peptides and proteins in living systems. However, D- amino acids were recently detected in various living organisms, including mammals. Of these D-amino acids, D-serine has been most extensively studied. D-Serine was found to play an important role as a neurotransmitter in the human central nervous system (CNS) by binding to the N-methyl- D-aspartate receptor (NMDAr). D-Serine binds with high affinity to a co-agonist site at the NMDAr and, along with glutamate, mediates several vital physiological and pathological processes, including NMDAr transmission, synaptic plasticity and neurotoxicity. Therefore, a key role for D-serine as a determinant of NMDAr mediated neurotransmission in mammalian CNS has been suggested. In this context, we review the known functions of D-serine in human physiology, such as CNS development, and pathology, such as neuro-psychiatric and neurodegenerative diseases related to NMDAr dysfunction.

E. coli histidine triad nucleotide binding protein 1 (ecHinT) is a catalytic regulator of D-alanine dehydrogenase (DadA) activity in vivo.

Histidine triad nucleotide binding proteins (Hints) are highly conserved members of the histidine triad (HIT) protein superfamily. Hints comprise the most ancient branch of this superfamily and can be found in Archaea, Bacteria, and Eukaryota. Prokaryotic genomes, including a wide diversity of both Gram-negative and Gram-positive bacteria, typically have one Hint gene encoded by hinT (ycfF in E. coli). Despite their ubiquity, the foundational reason for the wide-spread conservation of Hints across all kingdoms of life remains a mystery. In this study, we used a combination of phenotypic screening and complementation analyses with wild-type and hinT knock-out Escherichia coli strains to show that catalytically active ecHinT is required in E. coli for growth on D-alanine as a sole carbon source. We demonstrate that the expression of catalytically active ecHinT is essential for the activity of the enzyme D-alanine dehydrogenase (DadA) (equivalent to D-amino acid oxidase in eukaryotes), a necessary component of the D-alanine catabolic pathway. Site-directed mutagenesis studies revealed that catalytically active C-terminal mutants of ecHinT are unable to activate DadA activity. In addition, we have designed and synthesized the first cell-permeable inhibitor of ecHinT and demonstrated that the wild-type E. coli treated with the inhibitor exhibited the same phenotype observed for the hinT knock-out strain. These results reveal that the catalytic activity and structure of ecHinT is essential for DadA function and therefore alanine metabolism in E. coli. Moreover, they provide the first biochemical evidence linking the catalytic activity of this ubiquitous protein to the biological function of Hints in Escherichia coli.

Fatty Acids Analysis, Antioxidant and Biological Activity of Fixed Oil of Annona muricata L. Seeds

The total oil yield and the fatty acid composition were determined in the Annona muricata L. fixed oil using organic solvent extraction and GC-FID. The seeds were found to contain about ~21.5% of crude fixed oil on a dry weight basis. The crude oil containing fatty acid was converted into methyl esters and analysed by GC-FID. Fourteen fatty acids were identified using GC-FID. The major monounsaturated and saturated fatty acids were oleic acid (39.2%) and palmitic acid (19.1–19.2%), respectively, whereas the α-linolenic acid (1.2%) and linoleic acid (34.9%) were polyunsaturated fatty acid. The other saturated acids were stearic acid (3.3%), arachidic acid (0.4%), myristic acid (0.1%), heptadecanoic acid (0.1%), behenic acid (0.1%), and lignoceric acid (0.1%). Some of the fatty acids have not been reported earlier from the oil of Annona muricata L. Fixed oil exhibited significant free radical scavenging activity which was measured using DPPH and is also known to inhibit the gastrointestinal motility significantly.

Studies on the In Vitro Antiproliferative, Antimicrobial, Antioxidant, and Acetylcholinesterase Inhibition Activities Associated with Chrysanthemum coronarium Essential Oil

The essential oil of the Jordanian Chrysanthemum coronarium L. (garland) was isolated by hydrodistillation from dried flowerheads material. The oil was essayed for its in vitro scavenging activity using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) method. The results demonstrate that the oil exhibits moderate radical scavenging activity relative to the strong antioxidant ascorbic acid. In addition, cholinesterase inhibitory activity of C. coronarium essential oil was evaluated for the first time. Applying Ellmans colorimetric method, interesting cholinesterase inhibitory activity, which is not dose dependent, was evident for the oil. Furthermore, antimicrobial activities of the oil against both Gram-negative and Gram-positive bacteria were evaluated. While it fails to inhibit Gram-negative bacteria growth, the antibacterial effects demonstrated by the oil were more pronounced against the Gram-positive strains. Moreover, the examined oil was assessed for its in vitro antiproliferative properties where it demonstrated variable activities towards different human cancer cell lines, of which the colon cancer was the most sensitive to the oil treatment.

Molecular modeling based approach, synthesis, and cytotoxic activity of novel benzoin derivatives targeting phosphoinostide 3-kinase (PI3Kα).

The oncogenic potential of phosphatidylinositol 3-kinase (PI3Kα) has made it an attractive target for anticancer drug design. In this work, we describe our efforts to optimize the lead PI3Kα inhibitor 2-hydroxy-1,2-diphenylethanone (benzoin). A series of 2-oxo-1,2-diphenylethyl benzoate analogs were identified as potential PI3Kα inhibitors. Docking studies confirmed that the aromatic interaction is mediating ligand/protein complex formation and identified Lys802 and Val851 as H-bonding key residues. Our biological data in human colon carcinoma HCT116 showed that the structure analogs inhibited cell proliferation and induced apoptosis.

Computer-aided design, synthesis, and biological evaluation of new indole-2-carboxamide derivatives as PI3Kα/EGFR inhibitors

Structure-based drug design and molecular modeling were employed to identify a new series of indole-2-carboxamides as potential anticancer agents. These compounds were synthesized and characterized with the aid of several spectroscopic techniques, such as FT-IR, NMR, and mass spectrometry as well as by elemental analysis. Molecular docking studies confirmed that the newly synthesized compounds accommodate PI3Kα and EGFR kinase catalytic sites and form H-bonding with the key binding residues. The antitumor activity of these new compounds against an array of cancer cell lines (human colon carcinoma (HCT116), leukemia (K562), and breast cancer (MDA231) was evaluated. Results revealed that these compounds were selective against the kinase domain, and none of them showed any inhibitory activity against K562. In addition, results showed that compound 13 exhibited high potency in HCT116 and MDA231 with IC50 values of 19 and 15μM, respectively. Our findings recommend that further optimization of this series would be beneficial for colon and breast cancer treatment.