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Abozeid, D., G. Fawzy, M. Issa, N. Abdeltawab, and F. Soliman, "Medicinal plants and their constituents in the treatment of Acne vulgaris", Biointerface Research in Applied Chemistry, vol. 13, issue 2, pp. 189, 2023.
Kamal, I. M., N. F. Abdeltawab, Y. M. Ragab, M. A. Farag, and M. A. Ramadan, "Biodegradation, Decolorization, and Detoxification of Di-Azo Dye Direct Red 81 by Halotolerant, Alkali-Thermo-Tolerant Bacterial Mixed Cultures.", Microorganisms, vol. 10, issue 5, 2022. Abstract

Azo dyes impact the environment and deserve attention due to their widespread use in textile and tanning industries and challenging degradation. The high temperature, pH, and salinity used in these industries render industrial effluent decolorization and detoxification a challenging process. An enrichment technique was employed to screen for cost-effective biodegraders of Direct Red 81 (DR81) as a model for diazo dye recalcitrant to degradation. Our results showed that three mixed bacterial cultures achieved ≥80% decolorization within 8 h of 40 mg/L dye in a minimal salt medium with 0.1% yeast extract (MSM-Y) and real wastewater. Moreover, these mixed cultures showed ≥70% decolorization within 24 h when challenged with dye up to 600 mg/L in real wastewater and tolerated temperatures up to 60 °C, pH 10, and 5% salinity in MSM-Y. Azoreductase was the main contributor to DR81 decolorization based on crude oxidative and reductive enzymatic activity of cell-free supernatants and was stable at a wide range of pH and temperatures. Molecular identification of azoreductase genes suggested multiple genes per mixed culture with a possible novel azoreductase gene. Metabolite analysis using hyphenated techniques suggested two reductive pathways for DR81 biodegradation involving symmetric and asymmetric azo-bond cleavage. The DR81 metabolites were non-toxic to nauplii and seeds. This study provided evidence for DR81 degradation using robust stress-tolerant mixed cultures with potential use in azo dye wastewater treatment.

Habib, B. A., N. F. Abdeltawab, and I. S. Ad-din, "D-optimal mixture design for optimization of topical dapsone niosomes: in vitro characterization and in vivo activity against .", Drug delivery, vol. 29, issue 1, pp. 821-836, 2022. Abstract

This study aimed to illustrate the use of D-optimal mixture design (DOMD) for optimization of an enhancer containing Dapsone niosomal formula for acne topical treatment. Mixture components (MixCs) studied were: Span 20, Cholesterol, and Cremophor RH. Different responses were measured. Optimized formula (OF) was selected to minimize particle size and maximize absolute zeta potential and entrapment efficiency. Optimized formula gel (OF-gel) was prepared and characterized. OF-gel in vivo skin penetration using confocal laser scanning microscopy and activity against in acne mouse model were studied. Based on DOMD results analysis, adequate models were derived. Piepel and contour plots were plotted accordingly to explain how alteration in MixCs L-pseudo values affected studied responses and regions for different responses' values. The OF had suitable predicted responses which were in good correlation with the actually measured ones. The OF-gel showed suitable characterization and in vivo skin penetration up to the dermis layer. In vivo acne mouse-model showed that OF-gel-treated group (OF-gel-T-gp) had significantly better recovery (healing) criteria than untreated (UT-gp) and Aknemycin-treated (A-T-gp) groups. This was evident in significantly higher reduction of inflammation percent observed in OF-gel-T-gp than both UT-gp and A-T-gp. Better healing in OF-gel-T-gp compared with other groups was also verified by histopathological examination. Moreover, OF-gel-T-gp and A-T-gp bacterial loads were non-significantly different from each other but significantly lower than UT-gp. Thus, DOMD was an adequate statistical tool for optimization of an appropriate enhancer containing Dapsone niosomal formula that proved to be promising for topical treatment of acne.

Mohamed, S. S., N. F. Abdeltawab, W. Wadie, L. A. Ahmed, R. M. Ammar, S. Rabini, H. Abdel-Aziz, and M. T. Khayyal, "Effect of the standard herbal preparation, STW5, treatment on dysbiosis induced by dextran sodium sulfate in experimental colitis.", BMC complementary medicine and therapies, vol. 21, issue 1, pp. 168, 2021. Abstract

BACKGROUND: The standardized herbal preparation, STW 5, is effective clinically in functional gastrointestinal disorders and experimentally in ulcerative colitis (UC). The present study explores whether the beneficial effect of STW 5 involves influencing the intestinal microbiota.

METHODS: UC was induced in Wistar rats by feeding them 5% dextran sodium sulfate (DSS) in drinking water for 7 days. Rats were treated concurrently with STW 5 and sacrificed 24 h after last drug administration. Fecal samples were used to determine changes in the abundance of selected microbial phyla and genera using real-time PCR.

RESULTS: Induction of UC led to dysbiosis and changes in the gut microbiota. The changes included an increase in some genera of the Firmicutes, namely Enterococcus, and a decrease in others, namely Blautia, Clostridium, and Lactobacillus. DSS further induced a marked increase in the abundance of Bacteroidetes and Proteobacteria as well as in the relative abundance of Actinobacteria and its genus Bifidobacterium. Methanobrevibacter levels (phylum Euryarchaeota) were also increased. Microbial dysbiosis was associated with changes in various parameters of colonic inflammation. STW 5 effectively guarded against those changes and significantly affected the indices of edema and inflammation in the UC model. Changes in colon length, colon mass index, inflammatory and apoptotic markers, and histological changes induced by DSS were also prevented.

CONCLUSIONS: Dysbiosis plays a contributing role in the development of DSS-induced UC. Derangements in the microbial flora and associated inflammatory processes were largely prevented by STW 5, suggesting that this effect might contribute towards its beneficial usefulness in this condition.

Moussa, H. A., R. Wasfi, N. F. Abdeltawab, and S. A. Megahed, "High Counts and Anthracene Degradation Ability of and Isolated From the Oral Cavity of Cigarette Smokers and Non-smokers.", Frontiers in microbiology, vol. 12, pp. 661509, 2021. Abstractfmicb-12-661509.pdf

The composition and metabolic functions of oral microbiota are affected by many factors including smoking leading to several health problems. Cigarette smoking is associated with changes in oral microbiota composition and function. However, it is not known if the depletion of certain bacterial genera and species is due to specific toxins in cigarette smoke, or indirectly due to competition for colonization with smoking-enriched bacteria. Therefore, the aim of this study was to determine the effect of cigarette smoking on the microbial prevalence and polycyclic aromatic hydrocarbons (PAHs) biodegradation of selected enriched and depleted oral bacteria from oral microbiota of smokers compared to that in non-smokers. Samples of oral rinse from smokers and non-smokers were collected ( = 23, 12 smokers and 11 non-smokers) and screened for oral bacterial strains of spp., and spp. Comparing counts, , , and showed higher counts in smokers compared to non-smokers while the spp. were higher in non-smokers. was prevalent in smokers, representing 91.67% of the total Lactobacillus spp. isolates. The biodegradation potential of anthracene; a representative of PAHs of collected isolates, in single and mixed cultures, was assayed with anthracene as the sole source of carbon using 2,6-dichlorophenol indophenol (2,6-DCPIP) as indicator. isolates recovered from smokers showed higher degradation of anthracene compared to those recovered from non-smokers. The anaerobic anthracene biodegradation activity of isolates from non-smokers was the highest among all isolates of the three recovered genera from the same subject. The anthracene biodegradation potential of spp. was variable. Combinations of isolated bacteria in co-cultures showed that spp. interfered with anthracene biodegradation ability along with the viable counts of and spp. In conclusion, oral dysbiosis due to cigarette smoking was observed not only due to changes in oral bacterial relative abundance but also extended to bacterial functions such as anthracene biodegradation tested in this study. Microbe-microbe interactions changed the anthracene biodegradation potential and growth of the microbial mixture compared to their corresponding single isolates, and these changes differ according to the constituting bacteria.

Elhakim, Y. A., A. E. Ali, A. E. - D. M. S. Hosny, and N. F. Abdeltawab, "Zinc Deprivation as a Promising Approach for Combating Methicillin-Resistant Staphylococcus aureus: A Pilot Study", Pathogens, vol. 10, issue 10, pp. 1228, 2021.
Radwan, N. H., M. Nasr, R. A. H. Ishak, N. F. Abdeltawab, and G. A. S. Awad, "Chitosan-calcium phosphate composite scaffolds for control of post-operative osteomyelitis: Fabrication, characterization, and in vitro-in vivo evaluation.", Carbohydrate polymers, vol. 244, pp. 116482, 2020. Abstract

Osteomyelitis is a progressive inflammatory disease requiring prolonged systemic treatment with high antibiotic doses, and is very challenging to be treated. The use of locally applied antibiotics loaded on a biodegradable carrier at surgery sites is hypothesized to prevent post-operative osteomyelitis, while providing site-specific drug release. In this work, chitosan-based calcium phosphate composites were prepared and loaded with moxifloxacin hydrochloride. The in-situ formation of calcium phosphates within the composite was experimentally confirmed by Fourier transform infra-red spectroscopy, X-ray powder diffraction, and scanning electron microscopy. Results showed that the composites provided complete drug release over three days, and the selected composite formulation induced differentiation and proliferation of osteoblasts, while reducing bacterial count, inflammation and intra-medullary fibrosis in bone tissue specimens of osteomyelitis-induced animal model. Hence, we can conclude that the in situ prepared antibiotic-loaded calcium phosphate chitosan composite is promising in preventing post-operative osteomyelitis, and is worthy of clinical experimentation.

Haikal, S. M., N. F. Abdeltawab, L. A. Rashed, T. I. Abd El-Galil, H. A. Elmalt, and M. A. Amin, "Combination Therapy of Mesenchymal Stromal Cells and Interleukin-4 Attenuates Rheumatoid Arthritis in a Collagen-Induced Murine Model.", Cells, vol. 8, issue 8, 2019. Abstract

Rheumatoid arthritis (RA) is a disease of the joints that causes decreased quality of life. Mesenchymal stromal cells (MSCs) have immunosuppressive properties, with possible use in the treatment of RA. Similarly, interleukin (IL)-4 has been shown as a potential RA treatment. However, their combination has not been explored before. Therefore, this study aimed to investigate the effect of a combination therapy of MSCs and IL-4 in the treatment of RA, using a murine collagen-induced arthritis (CIA) model. Arthritis was induced in Balb/c mice by two intradermal injections of type II collagen (CII), at days 0 and 21. CIA mice were randomly assigned to four groups; group I received an intravenous injection of mouse bone marrow-derived MSCs, while group II received an intraperitoneal injection of IL-4. Group III received a combined treatment of MSC and IL-4, while group IV served as a CIA diseased control group receiving phosphate buffer saline (PBS). A fifth group of healthy mice served as the normal healthy control. To assess changes induced by different treatments, levels of RA-associated inflammatory cytokines and biomarkers were measured in the serum, knee joints, and synovial tissue, using ELISA and Real Time-qPCR. Histopathological features of knee joints were analyzed for all groups. Results showed that combined MSC and IL-4 treatment alleviated signs of synovitis in CIA mice, reverting to the values of healthy controls. This was evident by the decrease in the levels of rheumatic factor (RF), C-reactive protein (CRP) and anti-nuclear antibodies (ANA) by 64, 80, and 71%, respectively, compared to the diseased group. Moreover, tumor necrosis factor-alpha (TNF- α) and monocyte chemoattractant protein-1 (MCP-1) levels decreased by 63 and 68%, respectively. Similarly, our gene expression data showed improvement in mice receiving combined therapy compared to other groups receiving single treatment, where cartilage oligomeric matrix protein (Comp), tissue inhibitor metalloproteinase-1 (Timp1), matrix metalloproteinase1 (Mmp-1), and IL-1 receptor (Il-1r) gene expression levels decreased by 75, 70, and 78%, respectively. Collectively, treatment with a combined therapy of MSC and IL-4 might have an efficient therapeutic effect on arthritis. Thus, further studies are needed to assess the potential of different MSC populations in conjugation with IL-4 in the treatment of experimental arthritis.

Shamma, R. N., I. S. Ad-din, and N. F. Abdeltawab, "Dapsone- gel as a novel platform for acne treatment: In vitro evaluation and In vivo performance and histopathological studies in acne infected mice", Journal of Drug Delivery Science and Technology, vol. 54, issue 101238, pp. 101238, 2019. 2019_shamma_etal_dapsone.pdf
Gohar, A., N. F. Abdeltawab, N. Shehata, and M. A. Amin, "Preclinical study of safety and immunogenicity of combined rubella and human papillomavirus vaccines: Towards enhancing vaccination uptake rates in developing countries.", Papillomavirus research (Amsterdam, Netherlands), vol. 8, pp. 100172, 2019. Abstract

Rubella vaccine was not part of national immunization programs (NIP) in several countries in the Middle East and North Africa (MENA), South-East Asia (SEA), and South Africa regions until the year 2000. Therefore, immunization coverage of females older than 20 years old in these countries has been the focus of national campaigns for rubella elimination in developing countries. Vaccines against human papillomavirus (HPV) are not part of NIPs in developing countries. To enhance the advantages of rubella-directed immunization campaigns and to increase HPV vaccine uptake in developing countries, this study aimed to test the stability, potency, efficacy and safety of a combined rubella and HPV vaccine. Female BALB/c mice were immunized subcutaneously with proposed combined HPV16/HPV18 VLP and rubella vaccine at weeks (W) 0, 3 then with HPV vaccine at W 7. Immunized mice developed antigen-specific antibodies against rubella and HPV significantly higher than mice immunized with rubella or HPV vaccine alone. The combined vaccine induced significantly higher splenocyte proliferation than control groups. In addition, pro-inflammatory cytokines IL-4, IL-6, IL-2, and IFNγ levels were significantly higher in mice immunized with the combined vaccine than control groups. Overall, the combined vaccine was safe and immunogenic offering antibody protection as well as eliciting a cellular immune response against rubella and HPV viruses in a single vaccine. This combined vaccine can be of great value to females above 20 years old in the SEA, MENA and South Africa regions offering coverage to rubella vaccine and a potential increase in HPV vaccine uptake rates after appropriate clinical testing.

Taleb, M. H., N. F. Abdeltawab, R. N. Shamma, S. S. Abdelgayed, S. S. Mohamed, M. A. Farag, and M. A. Ramadan, "Origanum vulgare L. Essential Oil as a Potential Anti-Acne Topical Nanoemulsion-In Vitro and In Vivo Study.", Molecules, vol. 23, issue 9, pp. 2164–2179, 2018. researcharticle.pdf
El-Boghdady, N. A., N. F. Abdeltawab, and M. M. Nooh, "Resveratrol and Montelukast Alleviate Paraquat-Induced Hepatic Injury in Mice: Modulation of Oxidative Stress, Inflammation, and Apoptosis.", Oxidative medicine and cellular longevity, vol. 2017, pp. 9396425, 2017. Abstract

Paraquat (PQ) is one of the most used herbicide worldwide. Its cytotoxicity is attributed to reactive radical generation. Resveratrol (Res) and montelukast (MK) have anti-inflammatory and antioxidant properties. The protective effects of Res, MK, or their combination against PQ-induced acute liver injury have not been investigated before. Therefore, we explored the protective potential of Res and/or MK against PQ hepatic toxicity in a mouse model. Mice were randomly assigned to five groups: group I served as the normal control and group II received a single dose of PQ (50 mg/kg, i.p.). Groups III, IV, and V received PQ plus oral Res (5 mg/kg/day), MK (10 mg/kg/day), and Res/MK combination, respectively. Res and/or MK reduced PQ-induced liver injury, evidenced by normalization of serum total protein, ALT, and AST. Res and/or MK significantly reversed PQ-induced oxidative stress markers glutathione and malondialdehyde. Res and/or MK significantly reduced PQ-induced inflammation reflected in TNF-levels. Furthermore, Res and/or MK reversed PQ-induced apoptosis assessed by differential expression of,, and. Histopathologic examination supported the biochemical findings. Although Res and MK displayed antioxidative, anti-inflammatory, and antiapoptotic activities, their combination was not always synergistic.

Eid, S. Z., N. F. Abdeltawab, S. T. Melek, and M. A. Amin, "Schistosoma mansoni co-infection with hepatitis C virus is associated with increased interleukin-28B plasma levels in Egyptian population", Journal of the Egyptian Society of Parasitology, vol. 47, issue 2, pp. 363–374, 2017.
AbdelAllah, N. H., N. F. Abdeltawab, A. A. Boseila, and M. A. Amin, "Chitosan and Sodium Alginate Combinations Are Alternative, Efficient, and Safe Natural Adjuvant Systems for Hepatitis B Vaccine in Mouse Model.", Evidence-based complementary and alternative medicine : eCAM, vol. 2016, pp. 7659684, 2016. Abstract

Hepatitis B viral (HBV) infections represent major public health problem and are an occupational hazard for healthcare workers. Current alum-adjuvanted HBV vaccine is the most effective measure to prevent HBV infection. However, the vaccine has some limitations including poor response in some vaccinee and being a frost-sensitive suspension. The goal of our study was to use an alternative natural adjuvant system strongly immunogenic allowing for a reduction in dose and cost. We tested HBV surface antigen (HBsAg) adjuvanted with chitosan (Ch) and sodium alginate (S), both natural adjuvants, either alone or combined with alum in mouse model. Mice groups were immunized subcutaneously with HBsAg adjuvanted with Ch or S, or triple adjuvant formula with alum (Al), Ch, and S, or double formulations with AlCh or AlS. These were compared to control groups immunized with current vaccine formula or unadjuvanted HBsAg. We evaluated the rate of seroconversion, serum HBsAg antibody, IL-4, and IFN-γ levels. The results showed that the solution formula with Ch or S exhibited comparable immunogenic responses to Al-adjuvanted suspension. The AlChS gave significantly higher immunogenic response compared to controls. Collectively, our results indicated that Ch and S are effective HBV adjuvants offering natural alternatives, potentially reducing dose.

Russo, L. M., N. F. Abdeltawab, A. D. O'Brien, M. Kotb, and A. R. Melton-Celsa, "Mapping of genetic loci that modulate differential colonization by Escherichia coli O157:H7 TUV86-2 in advanced recombinant inbred BXD mice.", BMC genomics, vol. 16, pp. 947, 2015. Abstract

BACKGROUND: Shiga toxin (Stx)-producing E. coli (STEC) are responsible for foodborne outbreaks that can result in severe human disease. During an outbreak, differential disease outcomes are observed after infection with the same STEC strain. One question of particular interest is why some infected people resolve infection after hemorrhagic colitis whereas others progress to the hemolytic uremic syndrome (HUS). Host age and infection dose have been implicated; however, these parameters do not appear to fully account for all of the observed variation in disease severity. Therefore, we hypothesized that additional host genetic factors may play a role in progression to HUS.

METHODS AND RESULTS: To mimic the genetic diversity in the human response to infection by STEC, we measured the capacity of an O157:H7 outbreak isolate to colonize mouse strains from the advanced recombinant inbred (ARI) BXD panel. We first infected the BXD parental strains C57BL/6 J (B6) and DBA/2 J (D2) with either 86-24 (Stx2a+) or TUV86-2, an Stx2a-negative isogenic mutant. Colonization levels were determined in an intact commensal flora (ICF) infection model. We found a significant difference in colonization levels between the parental B6 and D2 strains after infection with TUV86-2 but not with 86-24. This observation suggested that a host factor that may be masked by Stx2a affects O157:H7 colonization in some genetic backgrounds. We then determined the TUV86-2 colonization levels of 24 BXD strains in the ICF model. We identified several quantitative trait loci (QTL) associated with variation in colonization by correlation analyses. We found a highly significant QTL on proximal chromosome 9 (12.5-26.7 Mb) that strongly predicts variation in colonization levels and accounts for 15-20 % of variance. Linkage, polymorphism and co-citation analyses of the mapped region revealed 36 candidate genes within the QTL, and we identified five genes that are most likely responsible for the differential colonization.

CONCLUSIONS: The identification of the QTL on chromosome 9 supports our hypothesis that individual genetic makeup affects the level of colonization after infection with STEC O157:H7.

Zumbrun, E. E., N. F. Abdeltawab, H. A. Bloomfield, T. B. Chance, D. K. Nichols, P. E. Harrison, M. Kotb, and A. Nalca, "Development of a murine model for aerosolized ebolavirus infection using a panel of recombinant inbred mice", Viruses, vol. 4, no. 12: Multidisciplinary Digital Publishing Institute, pp. 3468–3493, 2012. Abstract
Abdeltawab, N., L. Lu, R. Williams, and M. Kotb, "Meta-analysis of genes within QTLs of group A streptococcal sepsis and their expression QTLs reveal pathways modulating host differential response to streptococcal sepsis", BMC Bioinformatics, vol. 13, no. Suppl 12: BioMed Central Ltd, pp. A6, 2012. Abstract
Kansal, R. G., V. Datta, R. K. Aziz, N. F. Abdeltawab, S. Rowe, and M. Kotb, "Dissection of the Molecular Basis for Hypervirulence of an In Vivo—Selected Phenotype of the Widely Disseminated M1T1 Strain of Group A Streptococcus Bacteria", Journal of Infectious Diseases, vol. 201, no. 6: Oxford University Press, pp. 855–865, 2010. Abstract
Abdeltawab, N., R. Kansal, S. Rowe, L. Gardner, C. Brannen, M. Nooh, S. Mukundan, H. Abdelsamed, R. Attia, W. Taylor, et al., "Bioinformatics analysis of immune response to group A streptococcal sepsis integrating quantitative trait loci mapping with genome-wide expression studies", BMC Bioinformatics, vol. 9, no. Suppl 7: BioMed Central Ltd, pp. P6, 2008. Abstract
Kotb, M., R. W. Williams, N. Fathey, M. Nooh, S. Rowe, R. Kansal, and R. Aziz, "Biotools for Determining the Genetics of Susceptibility to Infectious Diseases and Expediting Research Translation Into Effective Countermeasures", National Institute of Allergy and Infectious Diseases, NIH: Springer, pp. 13–17, 2008. Abstract
Rutter, S. M., Genetic effects on environmental vulnerability to disease, , vol. 805: Wiley, 2008. Abstract
Kotb, M., N. Fathey, R. Aziz, S. Rowe, R. W. Williams, and L. Lu, "Unbiased forward genetics and systems biology approaches to understanding how gene–environment interactions work to predict susceptibility and outcomes of infections", Genetic Effects on Environmental Vulnerability to Disease: Wiley Online Library, pp. 156–167, 2008. Abstract