Biological and chemical strategies for exploring inter- and intra-kingdom communication mediated via bacterial volatile signals

Farag, Mohamed A,Song, Geun Cheol,Park, Yong-Soon,Audrain, Bianca,Lee, Soohyun,Ghigo, Jean-Marc,Kloepper, Joseph W,Ryu, Choong-Min Nature Publishing Group 2017 NATURE PROTOCOLS -ELECTRONIC EDITION- Vol.12 No.7

<P>Airborne chemical signals emitted by bacteria influence the behavior of other bacteria and plants. We present an overview of in vitro methods for evaluating bacterial and plant responses to bacterial volatile compounds (BVCs). Three types of equipment have been used to physically separate the bacterial test strains from either other bacterial strains or plants (in our laboratory we use either Arabidopsis or tobacco plant seedlings): a Petri dish containing two compartments (BI Petri dish); two Petri dishes connected with tubing; and a microtiter-based assay. The optimized procedure for the BI Petri dish system is described in this protocol and can be widely used for elucidation of potential function in interactions between diverse microbes and those plant and chemical volatiles emitted by bacteria that are most likely to mediate bacterial or plant responses to BVCs. We also describe a procedure for metabolome-based BVC profiling via dynamic (i.e., continuous airflow) or static headspace sampling using solid-phase microextraction (SPME). Using both these procedures, bacteria-bacteria communications and bacteria-plant interactions mediated by BVCs can be rapidly investigated (within 1-4 weeks).</P>

Dynamic Chemical Communication between Plants and Bacteria through Airborne Signals: Induced Resistance by Bacterial Volatiles

Farag, Mohamed A.,Zhang, Huiming,Ryu, Choong-Min Springer US 2013 Journal of chemical ecology Vol.39 No.7

<P>Certain plant growth-promoting rhizobacteria (PGPR) elicit induced systemic resistance (ISR) and plant growth promotion in the absence of physical contact with plants <I>via</I> volatile organic compound (VOC) emissions. In this article, we review the recent progess made by research into the interactions between PGPR VOCs and plants, focusing on VOC emission by PGPR strains in plants. Particular attention is given to the mechanisms by which these bacterial VOCs elicit ISR. We provide an overview of recent progress in the elucidation of PGPR VOC interactions from studies utilizing transcriptome, metabolome, and proteome analyses. By monitoring defense gene expression patterns, performing 2-dimensional electrophoresis, and studying defense signaling null mutants, salicylic acid and ethylene have been found to be key players in plant signaling pathways involved in the ISR response. Bacterial VOCs also confer induced systemic tolerance to abiotic stresses, such as drought and heavy metals. A review of current analytical approaches for PGPR volatile profiling is also provided with needed future developments emphasized. To assess potential utilization of PGPR VOCs for crop plants, volatile suspensions have been applied to pepper and cucumber roots and found to be effective at protecting plants against plant pathogens and insect pests in the field. Taken together, these studies provide further insight into the biological and ecological potential of PGPR VOCs for enhancing plant self-immunity and/or adaptation to biotic and abiotic stresses in modern agriculture.</P>

Effect of gelatin addition on fabrication of magnesium phosphate-based scaffolds prepared by additive manufacturing system

Farag, M.M.,Yun, H.s. North-Holland 2014 Materials letters Vol.132 No.-

A gelatin/magnesium phosphate (MgP) three-dimensional (3D) porous scaffold for use in bone tissue regeneration was developed through the combination of an additive manufacturing (AM) system and bone cement chemistry. Temperature during 3D manufacturing was carefully studied, due to its importance to sol-gel transition of gelatin. At 25<SUP>o</SUP>C, the addition of appropriate gelatin (<6wt%) content to MgP greatly improved the mechanical properties of ceramic scaffolds (compressive strength=16.7+/-1.9MPa) as well as initial cell affinity, and affected drug (lysozyme) release performance.

Oral carcinoma cuniculatum, an unacquainted variant of oral squamous cell carcinoma: A systematic review

Farag, Amina Fouad,Abou-Alnour, Dalia Ali,Abu-Taleb, Noha Saleh Korean Academy of Oral and Maxillofacial Radiology 2018 Imaging Science in Dentistry Vol.48 No.4

Purpose: Oral carcinoma cuniculatum is a rare well-differentiated variant of oral squamous cell carcinoma. The purpose was to systematically review its unique features to differentiate it from other variants as verrucous carcinoma, papillary squamous cell carcinoma and well-differentiated squamous cell carcinoma. Materials and Methods: A systematic review was performed using MEDLINE, Dentistry and Oral Sciences Source and PubMed databases and any existing articles related to the research subject missed in the search strategy to screen ones reporting cases occurring exclusively in the oral cavity in English literature. Variables analyzed included clinical, etiologic, imaging, histopatholgical features, treatment, follow-up and survival rates. Results: From 229 hits, 17 articles with 43 cases were included in the systematic review. Clinically it showed a female predilection with pain and/or ulceration of a relatively long duration and exudation being the most common symptoms. Histologically, it showed more endophytic features comprising well-differentiated squamous epithelium with absent or minimal cytological atypia and multiple keratin filled crypts or cuniculus. Inflammatory stromal reaction and discharging abscesses were reported in most of the cases. Bone destruction was predominant in most imaging features. Complete surgical resection with a safety margin was the treatment of choice in most of the cases with few recorded recurrence cases. Conclusion: Apprehensive knowledge of oral carcinoma cuniculatum unique features is essential to avoid its misdiagnosis and provide proper treatment especially for recurrent cases.

Review of the chemistry of first-generation Tau PET tracers

Farag, Ahmed Karam,Im, Changkeun,Kang, Choong Mo,Lee, Yong Jin Korean Society of Radiopharmaceuticals and Molecul 2020 Journal of radiopharmaceuticals and molecular prob Vol.6 No.1

Alzheimer's disease (AD) is one of the challenging conditions that have no cure, yet early diagnosis can help to control the disease. PET imaging of tau has several advantages, such as being a noninvasive, safe diagnostic technique that correlates directly with the disease progression. Many tau tracers have been reported to date; however, the chemical scaffolds of them fall in a narrow chemical window, and none was approved yet as none is entirely selective and sensitive to tau. These problems are being solved as new tracers emerge constantly. In this report, the first-generation tau tracers such as [¹¹C]PBB3, 2-arylquinoline (THK) series, [¹⁸F]T808, and [¹⁸F]AV-1451 ([¹⁸F]T807) are reviewed from an organic and radiochemistry perspective; thus the most effective chemical approach to synthesize these tracers is discussed. This would help to design novel tracers which can meet the challenges faced by the current tracers.

Synthesis and characterization of novel Cu2O/PVDF nanocomposites for flexible ferroelectric organic electronic memory devices

Farag S. Al-Hazmi,Dago M. de Leeuw,A.A. Al-Ghamdi,F.S. Shokr 한국물리학회 2017 Current Applied Physics Vol.17 No.9

Copper oxide nanoparticles loaded Poly(vinylidene fluoride) (PVDF) nanocomposites, at concentrations from 1 to 9 wt%, were developed by casting technique. The effect of the Cu2O nanoparticles on the structure, thermal, mechanical and dielectric properties of the PVDF were inspected. The scanning electron microscopy (FE-SEM) revealed the well dispersion of the Cu2O nanoparticles into the PVDF matrix up to 5 wt%. The X-ray diffraction (XRD) patterns and the infrared spectroscopy (FTIR) measurements implied that the inclusion of the Cu2O nanoparticles into the PVDF matrix leads to a transform of the non-polar semi-crystalline a-phase of the neat PVDF to highly crystallized polar b-phase. Moreover, an increase of the thermal stability and crystallinity of the PVDF after the incorporation of the Cu2O nanoparticles was achieved. The Cu2O/PVDF nanocomposites exhibited excellent cyclic mechanical property compared to the neat PVDF. The introduction of 5 wt% Cu2O nanoparticles into the PVDF composites resulted in remarkable increase of the dielectric constant by 13 times while the dielectric loss was very low. A device based on Al/5 wt% Cu2O doped PVDF/Pt structure is developed. This device shows ferroelectric hysteresis with butterfly like shape and exhibited remanent polarization of 11.2 mC/cm2 with coercive field of 49 MV/m. These superior properties enable the developed Cu2O/PVDF nanocomposite films to be a potential candidate in the field of ferroelectric organic electronic memory devices.

Novel LCK/FMS inhibitors based on phenoxypyrimidine scaffold as potential treatment for inflammatory disorders

Farag, Ahmed Karam,Elkamhawy, Ahmed,Londhe, Ashwini M.,Lee, Kyung-Tae,Pae, Ae Nim,Roh, Eun Joo Elsevier 2017 European Journal of Medicinal Chemistry Vol.141 No.-

<P><B>Abstract</B></P> <P>Tyrosine kinases including LCK and FMS are involved in inflammatory disorders as well as many types of cancer. Our team has designed and synthesized thirty novel pyrimidine based inhibitors targeting LCK, classified into four different series (amides, ureas, imines (Schiff base) and benzylamines). Twelve of them showed nanomolar IC<SUB>50</SUB> values. Compound <B>7g</B> showed excellent selectivity profile and was selectively potent over FMS kinase (IC<SUB>50</SUB> value of 4.6 nM). Molecular docking study was performed to help us rationalize the obtained results and predict the possible binding mode for our compounds in both LCK and FMS. Based on the obtained biological assay data and modelling results, a detailed SAR study was discussed. As a further testing regarding the anti-inflammatory effect of the new compounds, <I>in vitro</I> cellular assay over RAW 264.7 macrophages was performed. Compound <B>7g</B> exhibited excellent anti-inflammatory effect. Therefore, we report the design of novel phenoxypyrimidine derivatives as potent and selective LCK inhibitors and the discovery of <B>7g</B> as potent and selective FMS/LCK dual inhibitor for the potential application in inflammatory disorders including rheumatoid arthritis (RA).</P> <P><B>Highlights</B></P> <P> <UL> <LI> Potent LCK/FMS inhibitors have been designed and synthesized. </LI> <LI> Nanomolar IC<SUB>50</SUB> values over both kinases were obtained. </LI> <LI> Excellent selectivity for LCK/FMS over closely related kinases was found. </LI> <LI> <B>7g</B> showed excellent anti-inflammatory activity on RAW 264.7 macrophages cell line. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Analysis of Six-Phase Brushless DC Wind Generator with Variable-Speed Constant-Frequency Sinusoidal PWM Topology

Farag K. Abo-Elyousr,임근희 대한전기학회 2010 대한전기학회 학술대회 논문집 Vol.2010 No.7

This paper presents a single-phase variable-speed DC/AC sinusoidal PWM power converter. The proposed converter is designed to control the BLDC current using PI controller. Furthermore, a model for multi-phase BLDC generator describing its transient and steady-state operating conditions is analyzed in this paper. The simulated results demonstrate that fixed-frequency converter output voltage can be effectively obtained with constant input current.

First-in-class DAPK1/CSF1R dual inhibitors: Discovery of 3,5-dimethoxy-<i>N</i>-(4-(4-methoxyphenoxy)-2-((6-morpholinopyridin-3-yl)amino)pyrimidin-5-yl)benzamide as a potential anti-tauopathies agent

Farag, Ahmed Karam,Hassan, Ahmed H.E.,Jeong, Hyeanjeong,Kwon, Youngji,Choi, Jin Gyu,Oh, Myung Sook,Park, Ki Duk,Kim, Yun Kyung,Roh, Eun Joo Elsevier 2019 European journal of medicinal chemistry Vol.162 No.-

<P><B>Abstract</B></P> <P>Kinase irregularity has been correlated with several complex neurodegenerative tauopathies. Development of selective inhibitors of these kinases might afford promising anti-tauopathy therapies. While DAPK1 inhibitors halt the formation of tau aggregates and counteract neuronal death, CSF1R inhibitors could alleviate the tauopathies-associated neuroinflammation. Herein, we report the design, synthesis, biological evaluation, mechanistic study, and molecular docking study of novel CSF1R/DAPK1 dual inhibitors as multifunctional molecules inhibiting the formation of tau aggregates and neuroinflammation. Compound <B>3l</B>, the most potent DAPK1 inhibitor in the <I>in vitro</I> kinase assay (IC<SUB>50</SUB> = 1.25 μM) was the most effective tau aggregates formation inhibitor in the cellular assay (IC<SUB>50</SUB> = 5.0 μM). Also, compound <B>3l</B> elicited potent inhibition of CSF1R in the <I>in vitro</I> kinase assay (IC<SUB>50</SUB> = 0.15 μM) and promising inhibition of nitric oxide production in LPS-induced BV-2 cells (55% inhibition at 10 μM concentration). Kinase profiling and hERG binding assay anticipated the absence of off-target toxicities while the PAMPA-BBB assay predicted potentially high BBB permeability. The mechanistic study and selectivity profile suggest compound <B>3l</B> as a non-ATP-competitive DAPK1 inhibitor and an ATP-competitive CSF1R inhibitor while the <I>in silico</I> calculations illustrated binding of compound <B>3l</B> to the substrate-binding site of DAPK1. Hence, compound <B>3l</B> might act as a protein-protein interaction inhibitor by hindering DAPK1 kinase reaction through preventing the binding of DAPK1 substrates.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Multifunctional DAPK1 and CSF1R inhibitors for targeting tauopathies. </LI> <LI> <B>3l</B> shows good potency and excellent affinity and within-family selectivity for both kinases. </LI> <LI> Mechanistic study showed <B>3l</B> as non-ATP-competitive DAPK1 inhibitor and ATP-competitive CSF1R inhibitor. </LI> <LI> <B>3l</B> has tau aggregation inhibition and anti-neuroinflammatory activity in cellular assays. </LI> <LI> hERG binding and PAMPA assays revealed <B>3l</B> as a cardiosafe and has a high membrane penetration. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

부스트 컨버터의 피드백 보상 설계

Farag K. Abo-elyousr,조경애,임근희 대한전기학회 2012 대한전기학회 학술대회 논문집 Vol.2012 No.7