Mohamed Farag - Academia.edu (original) (raw)

Papers by Mohamed Farag

Org Biomol Chem, 2004

T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 4 2 8 9 3 O... more T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 4 2 8 9 3 O r g . B i o m o l . C h e m . , 2 0 0 4 , 2 , 2 8 9 3 -2 8 9 6 OBC www.rsc.org/obc A novel generation of 1-iodo-3-siloxy-1,3-butadienes has been developed by reacting trimethylsilyl iodide (TMS-I) with a,b-unsaturated ketones in dichloromethane at 0 °C without the use of any catalyst. The halo aldol reaction of these butadiene intermediates with aldehydes was efficiently carried out by using magnesium iodide as the catalyst. Twelve b-iodo-a,b-unsaturated-b-hydroxyketones (halo aldols) have been synthesized under the new condition with excellent geometric selectivity and good chemical yields (>80% chemical yields for 11 examples).

Plant Cell, Tissue and Organ Culture (PCTOC), 2015

Proceedings of the National Academy of Sciences of the United States of America, Jan 15, 2003

Several chemical changes in soil are associated with plant growth-promoting rhizobacteria (PGPR).... more Several chemical changes in soil are associated with plant growth-promoting rhizobacteria (PGPR). Some bacterial strains directly regulate plant physiology by mimicking synthesis of plant hormones, whereas others increase mineral and nitrogen availability in the soil as a way to augment growth. Identification of bacterial chemical messengers that trigger growth promotion has been limited in part by the understanding of how plants respond to external stimuli. With an increasing appreciation of how volatile organic compounds signal plants and serve in plant defense, investigations into the role of volatile components in plant-bacterial systems now can follow. Here, we present chemical and plant-growth data showing that some PGPR release a blend of volatile components that promote growth of Arabidopsis thaliana. In particular, the volatile components 2,3-butanediol and acetoin were released exclusively from two bacterial strains that trigger the greatest level of growth promotion. Furt...

Proceedings of the National Academy of Sciences of the United States of America, Jan 13, 2007

Cell suspensions of the model legume Medicago truncatula accumulated the isoflavonoid phytoalexin... more Cell suspensions of the model legume Medicago truncatula accumulated the isoflavonoid phytoalexin medicarpin in response to yeast elicitor or methyl jasmonate (MJ), accompanied by decreased levels of isoflavone glycosides in MJ-treated cells. DNA microarray analysis revealed rapid, massive induction of early (iso)flavonoid pathway gene transcripts in response to yeast elicitor, but not MJ, and differential induction by the two elicitors of sets of genes encoding transcription factors, ABC transporters, and beta-glucosidases. In contrast, both elicitors induced genes encoding enzymes for conversion of the isoflavone formononetin to medicarpin. Four MJ-induced beta-glucosidases were expressed as recombinant enzymes in yeast, and three were active with isoflavone glucosides. The most highly induced beta-glucosidase was nuclear localized and preferred flavones to isoflavones. The results indicate that the genetic and biochemical mechanisms underlying accumulation of medicarpin differ de...

Journal of Advanced Research, 2015

Today, most investigations of the plant metabolome tend to be based on either nuclear magnetic re... more Today, most investigations of the plant metabolome tend to be based on either nuclear magnetic resonance (NMR) spectroscopy or mass spectrometry (MS), with or without hyphenation with chromatography. Although less sensitive than MS, NMR provides a powerful complementary technique for the identification and quantification of metabolites in plant extracts. NMR spectroscopy, well appreciated by phytochemists as a particularly information-rich method, showed recent paradigm shift for the improving of metabolome(s) structural and functional characterization and for advancing the understanding of many biological processes. Furthermore, two dimensional NMR (2D NMR) experiments and the use of chemometric data analysis of NMR spectra have proven highly effective at identifying novel and known metabolites that correlate with changes in genotype or phenotype. In this review, we provide an overview of the development of NMR in the field of metabolomics with special focus on 2D NMR spectroscopic techniques and their applications in phytomedicines quality control analysis and drug discovery from natural sources, raising more attention at its potential to reduce the gap between the pace of natural products research and modern drug discovery demand.

Vaccine, 2012

DC vaccination is an option to overcome this. DC pulsed in vitro with HBV sub viral particles (HB... more DC vaccination is an option to overcome this. DC pulsed in vitro with HBV sub viral particles (HBVsvp) and used to immunize mice can activate HBV directed humoral and cellular immune responses. In the present study we vaccinated HBV transgenic mice as a model for chronic HBV infection and observed humoral and cellular immune responses. In these mice, the lacking immune response against HBV is mainly due to peripheral tolerance. HBVsvp, together with LPS as a co-activating molecule, were used for pulsing and in vitro activation of DC. HBV transgenic mice were injected with pulsed DC two times. Four weeks after DC vaccination humoral and cellular immune responses, viral antigen levels and liver histology were analyzed. DC vaccinated HBV-transgenic mice developed a strong HBV specific antibody and T-cell response after DC vaccination. Neither circulating HBV antigen levels nor viremia, however, were controlled. No liver damage was observed. These results demonstrate that in vitro activation of DC and loading with HBVsvp can overcome tolerance against HBV and reactivate B-and T-cell responses in HBV transgenic mice, but were not sufficient to lead to virus control in these mice. Vaccination using DC, the key players of cellular and humoral immunity, after in vitro reactivation promises to break tolerance against HBV and may help patients with chronic hepatitis B to clear the infection.

Planta, 2005

In response to insect feeding, corn plants (Zea mays cv. Delprim) release elevated levels of vola... more In response to insect feeding, corn plants (Zea mays cv. Delprim) release elevated levels of volatile organic compounds (VOCs), including the C 6 -volatile (Z)-3-hexenol. The level of mRNA accumulation for a series of defense genes was monitored in response to application of (Z)-3-hexenol (50 nmol) to undamaged plants. The induction of transcripts for hpl (hydroperoxide lyase), fps (farnesyl pyrophosphate synthase), pal (phenylalanine ammonia-lyase), lox (lipoxygenase), igl (indole-3-glycerol phosphate lyase) and mpi (maize proteinase inhibitor) were compared with metabolites generated from the respective pathways. While headspace VOC analysis showed an increase in (Z)-3-hexenyl acetate and methyl salicylate with lox and pal induction, respectively, MPI accumulation was not observed with an increase in mpi transcripts. Moreover, (Z)-3-hexenol treatment did not elevate sesquiterpene emissions or activate fps transcription. Chemical labeling and bioassay experiments established that exogenous (Z)-3-hexenol can be taken up and converted to a less active acetylated form. These data indicate that (Z)-3-hexenol can serve as a signaling molecule that triggers defense responses in maize and can rapidly be turned over in planta.

PLANT PHYSIOLOGY, 2009

Metabolic profiling of elicited barrel medic (Medicago truncatula) cell cultures using high-perfo... more Metabolic profiling of elicited barrel medic (Medicago truncatula) cell cultures using high-performance liquid chromatography coupled to photodiode and mass spectrometry detection revealed the accumulation of the aurone hispidol (6-hydroxy-2-[(4hydroxyphenyl)methylidene]-1-benzofuran-3-one) as a major response to yeast elicitor. Parallel, large-scale transcriptome profiling indicated that three peroxidases, MtPRX1, MtPRX2, and MtPRX3, were coordinately induced with the accumulation of hispidol. MtPRX1 and MtPRX2 exhibited aurone synthase activity based upon in vitro substrate specificity and product profiles of recombinant proteins expressed in Escherichia coli. Hispidol possessed significant antifungal activity relative to other M. truncatula phenylpropanoids tested but has not been reported in this species before and was not found in differentiated roots in which high levels of the peroxidase transcripts accumulated. We propose that hispidol is formed in cell cultures by metabolic spillover when the pool of its precursor, isoliquiritigenin, builds up as a result of an imbalance between the upstream and downstream segments of the phenylpropanoid pathway, reflecting the plasticity of plant secondary metabolism. The results illustrate that integration of metabolomics and transcriptomics in genetically reprogrammed plant cell cultures is a powerful approach for the discovery of novel bioactive secondary metabolites and the mechanisms underlying their generation.

Plant Molecular Biology, 2006

Previous studies have identified two distinct O-methyltransferases (OMTs) implicated in isoflavon... more Previous studies have identified two distinct O-methyltransferases (OMTs) implicated in isoflavonoid biosynthesis in Medicago species, a 7-OMT methylating the A-ring 7-hydroxyl of the isoflavone daidzein and a 4'-OMT methylating the B-ring 4¢-hydroxyl of 2,7,4¢-trihydroxyisoflavanone. Genes related to these OMTs from the model legume Medicago truncatula cluster as separate branches of the type I plant small molecule OMT family. To better understand the possible functions of these related OMTs in secondary metabolism in M. truncatula, seven of the OMTs were expressed in E. coli, purified, and their in vitro substrate preferences determined. Many of the enzymes display promiscuous activities, and some exhibit dual regio-specificity for the 4¢ and 7-hydroxyl moieties of the isoflavonoid nucleus. Protein structure homology modeling was used to help rationalize these catalytic activities. Transcripts encoding the different OMT genes exhibited differential tissue-specific and infection-or elicitor-induced expression, but not always in parallel with changes in expression of confirmed genes of the isoflavonoid pathway. The results are discussed in relation to the potential in vivo functions of these OMTs based on our current understanding of the phytochemistry of M. truncatula, and the difficulties associated with gene annotation in plant secondary metabolism.

Organic & Biomolecular Chemistry, 2004

Molecular Cancer, 2009

Background: Metabolic perturbations arising from malignant transformation have not been systemati... more Background: Metabolic perturbations arising from malignant transformation have not been systematically characterized in human lung cancers in situ. Stable isotope resolved metabolomic analysis (SIRM) enables functional analysis of gene dysregulations in lung cancer. To this purpose, metabolic changes were investigated by infusing uniformly labeled 13 C-glucose into human lung cancer patients, followed by resection and processing of paired non-cancerous lung and non small cell carcinoma tissues. NMR and GC-MS were used for 13 C-isotopomer-based metabolomic analysis of the extracts of tissues and blood plasma.

Journal of Obstetrics and Gynaecology Research, 2011

To evaluate uterine artery Doppler flow resistance and plasma adrenomedullin levels in women with... more To evaluate uterine artery Doppler flow resistance and plasma adrenomedullin levels in women with unexplained recurrent pregnancy loss (RPL) compared to controls.

Journal of Obstetrics and Gynaecology Research, 2007

To investigate the causes of maternal mortality in the Dakahlia Governorate in Egypt. A confident... more To investigate the causes of maternal mortality in the Dakahlia Governorate in Egypt. A confidential enquiry for each case of maternal mortality during the years 2004-2005 was carried out. One hundred and seventy-nine maternal deaths were reported, giving a maternal mortality rate (MMR) of 71.3/100,000 live births. 140 (78.2%) women died due to direct obstetric causes, 24 (13.4%) due to indirect causes and 15 (8.4%) due to accidental or unexplained causes. 44 (24.6%) women died during or following delivery by cesarean section and 91 (50.8%) during labor or within 24 h following delivery. Complications during cesarean delivery, postpartum hemorrhage and hypertensive disorders were the leading causes of maternal mortality. Death due to substandard care was encountered in 85% of cases. Obstetricians were responsible for 51% of causes of avoidable maternal death. Maternal mortality in Dakahlia, although declining, is still relatively high. To further reduce maternal mortality, deliveries should be conducted at well-equipped hospitals.

The Journal of Heart and Lung Transplantation, 2011

homing is crucial. Lung entrapment of intravenous (IV) injected MSCs has been implemented as the ... more homing is crucial. Lung entrapment of intravenous (IV) injected MSCs has been implemented as the main reason for inefficient cell number at the injured site. We found that the addition of a vasodilator, sodium-nitroprusside (SN) prior to IV MSC injection diminishes lung capillary entrapment. Despite SN pre-treatment the homing of exogenous MSCs to the infarct in our murine model of MI was still low. We sought out to determine whether cytokines released by the ischemic myocardium can enhance the recruitment and survival of infused MSC. Methods and Materials: Cytokines released by ischemic myocardium 24 hours after LAD ligations in mice were analysed for their potential to increase MSC migration and proliferation in vitro. Results: Many cytokines were at least 5-fold upregulated during ischemia, however in our in vitro studies only HGF and VEGF proved to promote both MSC proliferation and migration. Coinjection of MSCs and HGF or VEGF at the time of MI significantly increased the number of MSCs in the infarct. Left-ventricle ejection fraction (LVEF) was monitored 6 months after the MI using ECG-triggered contrast Micro-CT imaging. Treatment with IV injected MSC and HGF or VEGF attenuated the progressive decrease in LVEF. Surprisingly, LVEFs of mice that received HGF or VEGF alone, with no cell-based therapy, were similar to those groups that also received MSCs. Conclusions: Thus, our data show that HGF and VEGF attenuate negative LV remodeling after MI and reduce the mechanism of myocardium regeneration by MSC to a pure paracrine effect.

Journal of Experimental Botany, 2004

GC-MS-based metabolite profiling was used to analyse the response of Medicago truncatula cell cul... more GC-MS-based metabolite profiling was used to analyse the response of Medicago truncatula cell cultures to elicitation with methyl jasmonate (MeJa), yeast elicitor (YE), or ultraviolet light (UV). Marked changes in the levels of primary metabolites, including several amino acids, organic acids, and carbohydrates, were observed following elicitation with MeJa. A similar, but attenuated response was observed following YE elicitation, whereas little response was observed following UV elicitation. MeJa induced the accumulation of the triterpene b-amyrin, a precursor to the triterpene saponins, and LC-MS analysis confirmed the accumulation of triterpene saponins in MeJa-elicited samples. In addition, YE induced a slight, but significant accumulation of shikimic acid, an early precursor to the phenylpropanoid pathway, which was also demonstrated to be YE-inducible by LC-MS analyses. Correlation analyses of metabolite relationships revealed perturbation of the glycine, serine, and threonine biosynthetic pathway, and suggested the induction of threonine aldolase activity, an enzyme as yet uncharacterized from plants. Members of the branched chain amino acid pathway accumulated in a concerted fashion, with the strongest correlation being that between leucine and isoleucine (r 2 50.941). While UV exposure itself had little effect on primary metabolites, the experimental procedure, as revealed by control treatments, induced changes in several metabolites which were similar to those following MeJa elicitation. Sucrose levels were lower in MJ-and YE-elicited samples compared with control samples, suggesting that a portion of the effects observed on the primary metabolic pool are a consequence of fundamental metabolic repartitioning of carbon resources rather than elicitor-specific induction. In addition, b-alanine levels were elevated in all elicited samples, which, when viewed in the context of other elicitation responses, suggests the altered metabolism of coenzyme A and its esters, which are essential in secondary metabolism.

Journal of Chemical Ecology, 2013

Certain plant growth-promoting rhizobacteria (PGPR) elicit induced systemic resistance (ISR) and ... more Certain plant growth-promoting rhizobacteria (PGPR) elicit induced systemic resistance (ISR) and plant growth promotion in the absence of physical contact with plants via 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 2dimensional 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.