Browsing by Author "Tawfick, Mahmoud M"
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Item Antisense Tissue Factor Oligodeoxynucleotides Protected Diethyl Nitrosamine/Carbon Tetrachloride-Induced Liver Fibrosis Through Toll Like Receptor4-Tissue Factor-Protease Activated Receptor1 Pathway(Frontier, 2021-05) Shouman, Maha M; Abdelsalam, Rania M; Tawfick, Mahmoud M; Kenawy, Sanaa A; El-Naa, Mona MTissue factor (TF) is a blood coagulation factor that has several roles in many non-coagulant pathways involved in different pathological conditions such as angiogenesis, inflammation and fibrogenesis. Coagulation and inflammation are crosslinked with liver fibrosis where protease-activated receptor1 (PAR1) and toll-like receptor4 (TLR4) play a key role. Antisense oligodeoxynucleotides are strong modulators of gene expression. In the present study, antisense TF oligodeoxynucleotides (TFAS) was evaluated in treating liver fibrosis via suppression of TF gene expression. Liver fibrosis was induced in rats by a single administration of N-diethyl nitrosamine (DEN, 200 mg/kg; i. p.) followed by carbon tetrachloride (CCl4, 3 ml/kg; s. c.) once weekly for 6 weeks. Following fibrosis induction, liver TF expression was significantly upregulated along with liver enzymes activities and liver histopathological deterioration. Alpha smooth muscle actin (α-SMA) and transforming growth factor-1beta (TGF-1β) expression, tumor necrosis factor-alpha (TNF-α) and hydroxyproline content and collagen deposition were significantly elevated in the liver. Blocking of TF expression by TFAS injection (2.8 mg/kg; s. c.) once weekly for 6 weeks significantly restored liver enzymes activities and improved histopathological features along with decreasing the elevated α-SMA, TGF-1β, TNF-α, hydroxyproline and collagen. Moreover, TFAS decreased the expression of both PAR1 and TLR4 that were induced by liver fibrosis. In conclusion, we reported that blockage of TF expression by TFAS improved inflammatory and fibrotic changes associated with CCl4+DEN intoxication. In addition, we explored the potential crosslink between the TF, PAR1 and TLR4 in liver fibrogenesis. These findings offer a platform on which recovery from liver fibrosis could be mediated through targeting TF expression.Item Antisense Tissue Factor Oligodeoxynucleotides Protected Diethyl Nitrosamine/Carbon Tetrachloride-Induced Liver Fibrosis Through Toll Like Receptor4-Tissue Factor-Protease Activated Receptor1 Pathway(frontiersin, 05/11/2021) Shouman, Maha M; Abdelsalam, Rania M; Tawfick, Mahmoud M; Kenawy, Sanaa A; El-Naa, Mona MTissue factor (TF) is a blood coagulation factor that has several roles in many non-coagulant pathways involved in different pathological conditions such as angiogenesis, inflammation and fibrogenesis. Coagulation and inflammation are crosslinked with liver fibrosis where protease- activated receptor1 (PAR1) and toll-like receptor4 (TLR4) play a key role. Antisense oligodeoxynucleotides are strong modulators of gene expression. In the present study, antisense TF oligodeoxynucleotides (TFAS) was evaluated in treating liver fibrosis via suppression of TF gene expression. Liver fibrosis was induced in rats by a single administration of N-diethyl nitrosamine (DEN, 200 mg/kg; i. p.) followed by carbon tetrachloride (CCl4, 3 ml/kg; s. c.) once weekly for 6 weeks. Following fibrosis induction, liver TF expression was significantly upregulated along with liver enzymes activities and liver histopathological deterioration. Alpha smooth muscle actin (α-SMA) and transforming growth factor-1beta (TGF-1β) expression, tumor necrosis factor-alpha (TNF-α) and hydroxyproline content and collagen deposition were significantly elevated in the liver. Blocking of TF expression by TFAS injection (2.8 mg/kg; s. c.) once weekly for 6 weeks significantly restored liver enzymes activities and improved histopathological features along with decreasing the elevated α-SMA, TGF-1β, TNF-α, hydroxyproline and collagen. Moreover, TFAS decreased the expression of both PAR1 and TLR4 that were induced by liver fibrosis. In conclusion, we reported that blockage of TF expression by TFAS improved inflammatory and fibrotic changes associated with CCl4+DEN intoxication. In addition, we explored the potential crosslink between the TF, PAR1 and TLR4 in liver fibrogenesis. These findings offer a platform on which recovery from liver fibrosis could be mediated through targeting TF expression.Item High risk of potential diarrheagenic Bacillus cereus in diverse food products in Egypt(Allen press, 1/19/2020) Amin, Heba M; Tawfick, Mahmoud MBacillus cereus is one of the important foodborne pathogens that can be found in various foodstuffs; causing diarrheal and/or emetic syndromes. This study aimed to evaluate the prevalence, antimicrobial susceptibility profile, pathogenic potential, and genotypic diversity of B. cereus isolated from diverse food products from markets in Cairo, Egypt. A total of 39 out of 165 food samples were positive for B. cereus (detection rate of 24%) with a contamination level ranged from 2 to 6 log CFU/g and a higher incidence of > 3 log bacterial count. Antimicrobial susceptibility testing showed that B. cereus isolates were fully sensitive to all tested antimicrobial agents except β-lactams. The pathogenic potential of the 39 B. cereus isolates was assessed by detecting and profiling the secreted virulence or toxin encoding genes including the chromosomal-carried genes hblA , bceT , plc , sph , nheA , entFM , cytK associated with the diarrheal syndrome and the plasmid-carried ces gene associated with the emetic syndrome. The most frequently detected genes were hblA , nheA and entFM . All isolates harbored more than one of the diarrheal enterotoxins encoding genes with the genetic profile hblA-bceT-nheA-entFM-cytK-plc-sph was the most prevalent (in 20/39 isolates). The emetic toxin ces was not detected at all. ERIC-based analysis of the 20 B. cereus isolates harboring the prevalent genetic profile revelated that they were genetically distinct. In conclusion, the findings of this study provide useful information for public health management and serve as a warning of the potential risk of diarrheagenic B. cereus in diverse food products. Therefore, the consideration to extensively study the epidemiology of this food pathogen in Egypt is warranted. Additionally, strict procedures should be applied to monitor, protect, and safely handle food products, particularly ready to eat foodstuffs that are usually consumed without heat treatment.Item Occurrence and Molecular Study of Hypermucoviscous/Hypervirulence Trait in Gut Commensal K. pneumoniae from Healthy Subjects(MDPI AG, 2023-04) Osama, Dina M; Zaki, Bishoy M; Khalaf, Wafaa S; Mohamed, Marwa Yousry A; Tawfick, Mahmoud M; Amin, Heba MHypervirulent Klebsiella pneumoniae (hvKp) is emerging worldwide. Hypermucoviscousity is the characteristic trait that distinguishes it from classic K. pneumoniae (cKp), which enables Kp to cause severe invasive infections. This research aimed to investigate the hypermucoviscous Kp (hmvKp) phenotype among gut commensal Kp isolated from healthy individuals and attempted to characterize the genes encoding virulence factors that may regulate the hypermucoviscosity trait. Using the string test, 50 identified Kp isolates from healthy individuals’ stool samples were examined for hypermucoviscosity and investigated by transmission electron microscopy (TEM). Antimicrobial susceptibility profiles of Kp isolates were determined using the Kirby Bauer disc method. Kp isolates were tested for genes encoding different virulence factors by PCR. Biofilm formation was assayed by the microtiter plate method. All Kp isolates were multidrug-resistant (MDR). Phenotypically, 42% of isolates were hmvKp. PCR-based genotypic testing revealed the hmvKp isolates belonged to capsular serotype K2. All study Kp isolates harbored more than one virulence gene. The genes magA and rmpA were not detected, while the terW gene was present in all isolates. The siderophores encoding genes entB and irp2 were most prevalent in hmvKp isolates (90.5%) and non-hmvKp (96.6%), respectively. hmvKp isolates harbored the genes wabG and uge with rates of 90.5% and 85.7%, respectively. The outcomes of this research highlight the potential health risk of commensal Kp to cause severe invasive diseases, owing to being hmvKp and MDR, and harboring multiple virulence genes. The absence of essential genes related to hypermucoviscosity such as magA and rmpA in hmvKp phenotypes suggests the multifactorial complexity of the hypermucoviscosity or hypervirulence traits. Thus, further studies are warranted to verify the hypermucoviscosity-related virulence factors among pathogenic and commensal Kp in different colonization niches.Item Virulence traits-based behavior of Streptococcus mutans bacteria from dental plaque and dental caries conditions(جامعة قناة السويس, 04/11/2021) Abo Bakr, Rana A; Tawfick, Mahmoud M; Mostafa, Zeinab A; Abdulall, Abeer KStreptococcus mutans has significant virulence factors associated with the etiology and pathophysiology of dental plaque and caries through adherence to the tooth surface and biofilm formation. These microbes can tolerate and survive the acidic environment. The study aimed to compare the behavior of the S. mutans isolates from dental plaque and caries conditions, in addition to the evaluation of the biofilm formation by S. mutans with oral microbiota (Candida albicans). A total of 106 S. mutans isolates were recovered including 56 isolates from soft caries lesions, 30 isolates from the plaque of caries active and 20 isolates from the plaque of caries- free samples. The isolates' virulence efficacy was assessed phenotypically by acid production, acid tolerance, and biofilm formation assays. PCR detected genes encoding these virulence traits. There was a significant difference (p < 0.05) between the three groups of isolates in biofilm formation, biofilm formation when co-cultivated with C. albicans, pH reduction by acid production, but there was no significant difference in withstanding acidic pH. S. mutans isolates harbored the genes glucosyltransferase B (gtfB), glucan binding protein B (gbpB), F1F0 membrane-bound proton-translocating ATPase C subunit (atpH) and lactate dehydrogenase (ldh) which are responsible for biofilm formation, sucrose- dependent adhesion, acid tolerance and acid production, respectively. In conclusion, S. mutans isolates from caries-free and caries active dental plaque and dental caries conditions showed different virulence efficacy-based behaviour. C. albicans enhances the biofilm formation by S. mutans. Further investigation of factors influencing variable behavior of S. mutans bacteria from different lesions is warranted.