Ibrahim, K. A., M. K. El-Ashrey, M. O. N. A. T. KASHEF, and O. M. N. E. Y. A. M. HELMY, "Alanine racemase a promising Helicobacter pylori drug target inhibited by propanoic acid.", Microbes and infection, vol. 25, issue 7, pp. 105167, 2023. Abstract

Eradication of Helicobacter pylori, the class 1 carcinogen, faces several obstacles, which demand alternative options to conventional drug development methods. Alanine racemase (Alr) was proposed as H. pylori drug target, inhibited by propanoic acid (PA), in a previous in silico study. We investigated the possible treatment of H. pylori infection through Alr inhibition. A new model of H. pylori Alr was built, validated, and the binding of PA to the active site was modelled via molecular docking with a good docking score. PA minimum inhibitory concentration (MIC) against H. pylori ATCC 43504 and six H. pylori clinical isolates ranged from 312.5 to 416.7 ± 180 μg/ml and remained unchanged after 14 serial passages in increasing PA concentrations. The minimum bactericidal concentration of PA was 625 μg/ml. Selective Alr inhibition was confirmed by a significant PA MIC increase with increasing d-alanine concentrations. Similar PA MIC in other tested pathogens was recorded (312.5-625 μg/ml). PA lacked cytotoxicity in tested cell lines and efficiently eradicated H. pylori in a rat infection model. In conclusion, Alr is a promising broad-spectrum drug target, inhibited by PA without resistance development by repeated exposure for 14 serial passages.

AlEraky, D. M., H. M. Abuohashish, A. S. Bugshan, M. M. Abdelsalam, H. A. AlHawaj, T. T. AlKhamis, F. A. AlDossary, N. M. Alrayes, Y. M. Ragab, Z. AbdelKhalek, et al., "Potential Antigenic Candidates for the Development of Peptide-Based Vaccines to Induce Immunization against Infection in BALB/c Mice.", International journal of molecular sciences, vol. 23, issue 21, 2022. Abstract
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() has been identified as a group-1 definite carcinogen. As of yet, there is no available vaccine for this microorganism. Our study aimed to identify antigenic peptides in using an in silico proteomic approach, and to evaluate their effectiveness as potential vaccine candidates. Four different peptide sequences were prioritized using the reverse vaccinology, namely, CagA, CagA, VacA, and SabA. Peptides emulsified with Freunde's adjuvant were used to immunize BALB/C mice. Subcutaneously immunized mice were challenged by oral administration of IgG, IgA, IL4, and IL17 were detected in mice sera. Histopathology of the dissected stomach of vaccinated and control mice were assessed using H&E stain. IgG was significantly higher in mice vaccinated with SabA. IL-4 was significantly increased in CagA, CagA, VacA, and SabA vaccinated mice compared to the adjuvant group. Additionally, histopathological examination of gastric tissue showed a protective effect in the vaccinated groups compared to adjuvant and PBS groups. Our findings indicate a promising effect of the tested epitopes, particularly the SabA antigen, to induce an immune response against .

Ibrahim, K. A., M. O. N. A. T. KASHEF, T. R. Elkhamissy, M. A. Ramadan, and O. M. N. E. Y. A. M. HELMY, "Aspartate α-decarboxylase a new therapeutic target in the fight against infection.", Frontiers in microbiology, vol. 13, pp. 1019666, 2022. Abstract
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Effective eradication therapy for is a worldwide demand. Aspartate α-decarboxylase (ADC) was reported as a drug target in . , in an study, with malonic acid (MA) as its inhibitor. We evaluated eradicating . infection through ADC inhibition and the possibility of resistance development. MA binding to ADC was modeled molecular docking. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of MA were determined against . ATCC 43504, and a clinical . isolate. To confirm selective ADC inhibition, we redetermined the MIC in the presence of products of the inhibited enzymatic pathway: β-alanine and pantothenate. HPLC was used to assay the enzymatic activity of . 6x-his tagged ADC in the presence of different MA concentrations. . strains were serially exposed to MA for 14 passages, and the MICs were determined. Cytotoxicity in different cell lines was tested. The efficiency of ADC inhibition in treating . infections was evaluated using a Sprague-Dawley (SD) rat infection model. MA spectrum of activity was determined in different pathogens. MA binds to . ADC active site with a good docking score. The MIC of MA against . ranged from 0.5 to 0.75 mg/mL with MBC of 1.5 mg/mL. Increasing β-alanine and pantothenate concentrations proportionally increased MA MIC. The 6x-his tagged ADC activity decreased by increasing MA concentration. No resistance to ADC inhibition was recorded after 14 passages; MA lacked cytotoxicity in all tested cell lines. ADC inhibition effectively eradicated . infection in SD rats. MA had MIC between 0.625 to 1.25 mg/mL against the tested bacterial pathogens. In conclusion, ADC is a promising target for effectively eradicating . infection that is not affected by resistance development, besides being of broad-spectrum presence in different pathogens. MA provides a lead molecule for the development of an anti-helicobacter ADC inhibitor. This provides hope for saving the lives of those at high risk of infection with the carcinogenic . .

Taha, A. M., M. M. Aboulwafa, H. Zedan, and O. M. N. E. Y. A. M. HELMY, "Ramucirumab combination with sorafenib enhances the inhibitory efect of sorafenib on HepG2 cancer cells", Scientific reports, vol. 12, pp. 1-16, 2022. s41598-022-21582-w.pdf
Hallol, M., O. Helmy, A. - E. Shawky, A. El-Batal, and M. R. O. A. - A. P. L. B. I. I. of by a paramycoides and on Chitosan, "Optimization of Alpha-Amylase Production by a Local Bacillus paramycoides Isolate and Immobilization on Chitosan-Loaded Barium Ferrite Nanoparticles", Fermentation, vol. 8, issue 5, 2022. fermentation-08-00241-v2.pdf
Hagras, S. A. A., A. E. - D. M. S. Hosny, O. M. N. E. Y. A. M. HELMY, M. M. Salem-Bekhit, F. Shakeel, and H. A. Farrag, "Effect of sub-inhibitory concentrations of cefepime on biofilm formation by Pseudomonas aeruginosa.", Canadian journal of microbiology, vol. 67, issue 12, pp. 894-901, 2021. Abstract

This study investigated the effect of cefepime at sub-minimum inhibitory concentrations (sub-MICs) on in vitro biofilm formation (BF) by clinical isolates of . The effect of cefepime at sub-MIC levels (½-/ MIC) on in vitro BF by six clinical isolates of was phenotypically assessed following 24 and 48 h of challenge using the tissue culture plate (TCP) assay. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to observe the change in expression of three biofilm-related genes, namely, a protease-encoding gene (), fimbrial protein-encoding gene (), and alginate-encoding gene (), in a weak biofilm-producing strain of following 24 and 48 h of challenge with sub-MICs of cefepime. The BF morphology in response to cefepime was imaged using scanning electron microscopy (SEM). The TCP assay showed strain-, time-, and concentration-dependent changes in in vitro BF in following challenge with sub-MICs of cefepime, with a profound increase in strains with inherently no or weak biofilm-producing ability. RT-PCR revealed time-dependent upregulation in the expression of the investigated genes following challenge with ½ and ¼ MIC levels, as confirmed by SEM. Cefepime at sub-MICs could upregulate the expression of BF-related genes and enhance BF by clinical isolates.

El-Korany, S. M., O. M. N. E. Y. A. M. HELMY, A. M. El-Halawany, Y. E. Ragab, and H. H. Zedan, "Kojic acid repurposing as a pancreatic lipase inhibitor and the optimization of its production from a local Aspergillus oryzae soil isolate", BMC Biotechnology, vol. 20, issue 52, pp. 1-16, 2020. s12896-020-00644-9.pdf
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Ibrahim, K. A., O. M. N. E. Y. A. M. HELMY, M. O. N. A. T. KASHEF, T. R. Elkhamissy, and M. A. Ramadan, "Identification of Potential Drug Targets in Helicobacter pylori Using In Silico Subtractive Proteomics Approaches and Their Possible Inhibition through Drug Repurposing", Pathogens, vol. 9, issue 747, pp. 1-21, 2020.
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