Background: We propose a new approach based on genetic distances among viral strains to infer abo... more Background: We propose a new approach based on genetic distances among viral strains to infer about risk exposures and location of transmission at population level. Methods: We re-analysed 133 viral sequences obtained during a cross-sectional survey of 4020 subjects living in a hepatitis C virus (HCV) endemic area in 2002. A permutation test was used to analyze the correlation between matrices of genetic distances in the NS5b region of all pairwise combinations of the 133 viral strains and exposure status (jointly exposed or not) to several potential HCV risk factors. Results: Compared to subjects who did not share the same characteristics or iatrogenic exposures, the median Kimura genetic distances of viral strains were significantly smaller between brothers and sisters (0.031 versus 0.102, P,0.001), mother and child (0.044 versus 0.102, P,0.001), father and child (0.045 versus 0.102, P,0.001), or subjects exposed to periodontal treatment (0.084 versus 0.102, P = 0.02). Conversely, viral strains were more divergent between subjects exposed to blood transfusions (0.216 versus 0.102, P = 0.04) or tooth filling or extraction (0.108, versus 0.097, P = 0.05), suggesting acquisition of the virus outside of the village. Conclusion: This method provided insights on where infection took place (household, village) for several sociodemographic characteristics or iatrogenic procedures, information of great relevance for targeting prevention interventions. This method may have interesting applications for virologists and epidemiologists studying transmission networks in health-care facilities or among intravenous drug users.
Phosphorus Sulfur and Silicon and The Related Elements, Mar 1, 2002
ABSTRACT Some of novel N , N '-bis-(1,2,4-triazin-4-yl)dicarboxylic acid amides ( 2-5 ) a... more ABSTRACT Some of novel N , N '-bis-(1,2,4-triazin-4-yl)dicarboxylic acid amides ( 2-5 ) and thiadiazolo[2,3- b ][1,2,4]triazin-7-yl carboxylic acid derivatives ( 6 , 7 ) were prepared by heating 4-amino-6-methyl-5-oxo-3-thioxo-2,3,4,5-tetrahydro-1,2,4-triazine ( 1 ) with different dicarboxylic acids (oxalic, malonic, fumaric, maleic, succinic, and phthalic acids respectively) in POCl 3 . Refluxing 1 with 1-chloro-2,4-dinitrobenzene in DMF yielded 3-methyl-6-nitro-10 H -benzo[1,2,4]thiadiazino[2,3- c ][1,2,4]triazin-4-one ( 8 ). Condensation of 1 with 2,4-pentandione in refluxing acetic acid furnished 6-methyl-4-(1-methyl-3-oxobut-1-enylamino)-3-thioxo-3,4-dihydro-2 H -[1,2,4]triazin-5-one ( 9 ). 3,8-D imethyl[1,2,4] triazino[3,4- b ][1,3,4]thiadiazine-4,7-dione ( 11 ) was prepared by refluxing 1 with 2-bromopropionyl bromide in anhydrous benzene to afford the corresponding N -acetylated derivative 10 , which was cyclized by using triethylamine. Also, some triazinylquinazolinones 13a , b were obtained by fusion of 1 with 6-bromo(and/or 6,8-dibromo)-2-methyl-3,1-benzoxazin-4 H -ones.
Background and aims: According to the literature, 14-46% of subjects clear hepatitis C virus (HCV... more Background and aims: According to the literature, 14-46% of subjects clear hepatitis C virus (HCV) from blood after infection. Controversy exists about sex differences in HCV clearance rates. Patients and methods: We compared HCV clearance in males and females using data from a large population based study on HCV infection in Egypt. Definitions used in the paper were: cleared HCV infection (positive HCV antibody and negative HCV RNA test results) and chronic HCV infection (positive HCV antibody and positive HCV RNA test results). The study sample included 4720 village residents aged 18-65 years recruited through home based visits (n = 2425) or voluntary screening (n = 2295). Results: Overall, HCV antibody prevalence was 910/4720 (19.3% (95% confidence interval 18.2-20.4)). Of those with HCV antibodies (n = 910), 61.5% had chronic HCV infection. Compared with males, females were more likely to have cleared the virus (44.6% v 33.7%, respectively; p = 0.001). Control for age, schistosomiasis history, iatrogenic exposures, and sexual exposure to HCV did not alter the positive association between female sex and viral clearance. This study provides strong evidence in favour of a higher HCV clearance rate in females compared with males.
HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific re... more HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.
Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Introduction: Oxidative ... more Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Introduction: Oxidative stress plays an important role in hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCC). Glutathione S-transferases (GSTs) prevent oxidative stress associated cellular damage, catalyzing the conjugation of electrophilic compounds with glutathione. Partial or complete deletions of GST theta 1 (GSTT1) and mu 1 (GSTM1) have been associated with chronicity of HCV infection. However, data on the role of these null genotypes in progression to HCC is lacking. We investigated whether GSTT1 and GSTM1 modify the association between HCV and HCC in a case-control study in Egypt. Methods: Participants were recruited at the National Cancer Institute of Cairo University. Cases of HCC were confirmed on pathology, alpha-fetoprotein levels and imaging. Non-cancer controls, representative of the general population with respect to HCV prevalence, were frequency matched to cases on age, sex, and area of residence. HCV antibodies were measured in blood samples by enzyme-linked immunosorbent assay, and HCV RNA was measured by reverse transcription-polymerase chain reaction (RT-PCR). Homozygous deletions in GSTT1 and GSTM1 were determined by separate multiplex PCR methods. For these analyses, participants with active HBV were excluded. Logistic regression was used to analyze the risk of HCC associated with HCV after stratifying by GSTT1 and GSTM1 genotype. Additive interaction of HCV and null GST genotypes in HCC risk were determined by calculating the interaction contrast ratio (ICR). All analyses were adjusted for age, sex, current smoking, alcohol intake, urban/rural status, and pesticide use. Results: Compared to controls, HCC cases were more likely to be older, married, non-smokers, living in rural areas, and exposed to agricultural pesticides. HCV infection was a strong risk factor for HCC in this population [adjusted odds ratio (aOR): 13.6, 95% confidence interval (CI): 9.7-18.9]. GSTT1 and GSTM1 polymorphisms alone were not associated with HCC risk. However, the association of HCV with HCC was markedly stronger in patients with null GSTT1 genotype [aOR (95% CI): 23.9 (12.8-44.9) for null vs. 11.4 (7.6-17.1) for non-null]. The observations were similar for GSTM1 genotype [aOR (95% CI): 17.7 (11.1-28.5) for null vs. 10.0 (6.2-16.1) for non-null]. Additive positive interaction, as determined by an ICR value greater than zero, between HCV and null GSTT1 was significant for HCC risk [ICR (95% CI): 10.9 (2.6-41.9)]. However, the ICR for GSTM1 and HCV interaction was not statistically significant [ICR (95% CI): 2.9 (−1.7-11.1)]. Conclusions: Chronic HCV carriers with null GST genotypes are more likely to have HCC as compared to those with non-null genotypes. Studies are needed to confirm these findings and investigate the exact mechanisms underlying HCC susceptibility associated with the null GST genotypes in chronic HCV patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3752. doi:10.1158/1538-7445.AM2011-3752
Middle East Respiratory Syndrome (MERS) is a viral respiratory disease caused b a special type of... more Middle East Respiratory Syndrome (MERS) is a viral respiratory disease caused b a special type of coronavirus called MERS-CoV. In the search for effective substances against the MERS-CoV main protease, we looked into compounds from brown algae, known for their medicinal benefits. From a set of 1212 such compounds, our computer-based screening highlighted four-CMNPD27819, CMNPD1843, CMNPD4184, and CMNPD3156. These showed good potential in how they might attach to the MERS-CoV protease, comparable to a known inhibitor. We confirmed these results with multiple computer tests. Studies on the dynamics and steadiness of these compounds with the MERS-CoV protease were performed using molecular dynamics (MD) simulations. Metrics like RMSD and RMSF showed their stability. We also studied how these compounds and the protease interact in detail. An analysis technique, PCA, showed changes in atomic positions over time. Overall, our computer studies suggest brown algae compounds could be valuable in fighting MERS. However, experimental validation is needed to prove their real-world effectiveness.
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Background and Aim-Retrospective evaluation of hepatitis C virus (HCV) prevalence in lymphoma tis... more Background and Aim-Retrospective evaluation of hepatitis C virus (HCV) prevalence in lymphoma tissues has important applications in clarifying the contribution of viral factors to the pathogenesis. Trials for detection of HCV at the cellular level in lymphoma tissues are, so far, minimal with unsatisfactory results. We aimed to study the detection and localization of HCV in the tissues of B-cell non-Hodgkin lymphoma (NHL) patients. Design-We performed immunohistochemistry to detect the HCV nonstructural 3 protein in paraffin-embedded tissue specimens of B-cell NHL patients, in 39 serum HCV-RNA positive samples and 35 serum HCV-RNA negative samples as controls. The serum analysis was carried out for HCV antibodies using enzyme-linked immunoassay and for HCV-RNA using reverse transcription-polymerase chain reaction. Reverse transcription-polymerase chain reaction was used to detect the HCV-RNA in tissues in immunohistochemically positive cases. We correlated the results with the clinicopathologic characteristics of the patients. Results-A diffuse cytoplasmic immunohistochemical staining for HCV in the lymphoid cells was detected in 8 of 39 serum positive cases (20.5%), all of which were genotype 4, which is the most prevalent HCV genotype in Egypt. Only 2 out of 35 serum negative control samples showed positive staining and in 1 of them HCV-RNA was detected in tissue. No significant correlation was detected between HCV positive cases and the clinicopathologic features of the patients. Conclusions-Immunohistochemical detection of HCV proteins in lymphoma tissues supports a potential role of viral replication in lymphomagenesis. The low number of cases showing expression of viral proteins may represent a low viral load in lymphoid tissue and/or restriction of HCV protein expression to certain subtypes of B-cell NHL. Immunohistochemistry can be used as
Background and Aims: Neutrophils are the most abundant circulating leukocytes in humans. Recently... more Background and Aims: Neutrophils are the most abundant circulating leukocytes in humans. Recently, dual roles of tumorassociated neutrophils (TANs) within the multiple step paradigm of cancer have been recognized. Although there is the evidence for the existence of N1 (antitumoral) and N2 (protumoral) TANs, similar as M1 and M2 macrophage polarization, it also need to clarify neutrophil effector molecules, such as phenotypic molecular markers, which will contribute to further insights and will be crucial for therapeutical applications in cancer pathologies. Methods: Peripheral blood and intratumor neutrophils from 110 HCC patients assessed by flow cytometry. Immunocytochemistry were used to analyze the distribution and clinical relevance of neutrophils in 192 HCC patients. For functional analysis, human neutrophils are separated from by flow cytometry sorting and then co-cultured with CD4+/CD8+ effector T cells and tumor-specific antigen inducing CTLs for 48 h in vitro. Finally, in vivo analysis, the frequencies and function of neutrophils in peripheral blood. spleen and tumor are evaluated by flow cytometry. Results: We show here that the expression of programmed death ligand 1(PD-L1), which interacts with PD-1, is increased in neutrophils from HCC patients compared with healthy controls and chronic hepatitis B patients. The expression of PD-L1 was significantly up-regulated on neutrophils after exposure to tumor supernatant from hepatoma cells, and IL-1, IL-6, TNF-aand TGF-bis largely responsible for this up-regulation of PD-L1. Tumor environmental factors induce early transient expression of PD-L1 on neutrophils in tumor bearing mice. The PD-L1+ neutrophils effectively suppressed the proliferation of CD4+/CD8+ effector T cells and tumor-specific T cell immunity, the effect could be reversed by blocking PD-L1 on those neutrophils in vitro. Tumorbearing increased the frequencies of neutrophils in peripheral blood (mainly G2 population), bone marrow (mainly G3 population), and spleen (mainly G1 population). The infiltrating neutrophils in tumor showed high expression of PD-L1 and infiltrating CD3+ T cells showed high expression of PD-1, compared with peripheral blood and spleen in tumor-bearing mice. Conclusions: These data suggest that polarized neutrophils in peripheral blood and intratumor of hepatocellular carcinoma with the high expression of PD-L1 may contribute to maintenance of immunosuppression and foster immune privilege.
Monkeypox viral infection is an emerging threat and a major concern for the human population. The... more Monkeypox viral infection is an emerging threat and a major concern for the human population. The lack of drug molecules to treat this disease may worsen the problem. Identifying potential drug targets can significantly improve the process of developing potent drug molecules for treating monkeypox. The proteins responsible for viral replication are attractive drug targets. Identifying potential inhibitors from known drug molecules that target these proteins can be key to finding a cure for monkeypox. In this work, two viral proteins, DNA-dependent RNA polymerase (DdRp) and viral core cysteine proteinase, were considered as potential drug targets. Sixteen antibiotic drugs from the tetracycline class were screened against both viral proteins through high-throughput virtual screening. These tetracycline class of antibiotic drugs have the ability to inhibit bacterial protein synthesis, which makes these antibiotics drugs a prominent candidate for drug repurposing. Based on the screening...
The Ebola virus and its close relative, the Marburg virus, both belong to the family Filoviridae ... more The Ebola virus and its close relative, the Marburg virus, both belong to the family Filoviridae and are highly hazardous and contagious viruses. With a mortality rate ranging from 23% to 90%, depending on the specific outbreak, the development of effective antiviral interventions is crucial for reducing fatalities and mitigating the impact of Marburg virus outbreaks. In this investigation, a virtual screening approach was employed to evaluate 2042 natural compounds for their potential interactions with the VP35 protein of the Marburg virus. Average and worst binding energies were calculated for all 20 poses, and compounds that exhibited binding energies <−6 kcal/mol in both criteria were selected for further analysis. Based on binding energies, only six compounds (Estradiol benzoate, INVEGA (paliperidone), Isosilybin, Protopanaxadiol, Permethrin, and Bufalin) were selected for subsequent investigations, focusing on interaction analysis. Among these selected compounds, Estradiol ...
The World Health Organization (WHO) has designated the Zika virus (ZIKV) as a significant risk to... more The World Health Organization (WHO) has designated the Zika virus (ZIKV) as a significant risk to the general public’s health. Currently, there are no vaccinations or medications available to treat or prevent infection with the Zika virus. Thus, it is urgently required to develop a highly efficient therapeutic molecule. In the presented study, a computationally intensive search was carried out to identify potent compounds that have the potential to bind and block the activity of ZIKV NS5 RNA-dependent RNA polymerase (RdRp). The anti-dengue chemical library was subjected to high-throughput virtual screening and MM/GBSA analysis in order to rate the potential candidates. The top three compounds were then chosen. According to the MM/GBSA analysis, compound 127042987 from the database had the highest binding affinity to the protein with a minimum binding free energy of −77.16 kcal/mole. Compound 127042987 had the most stable RMSD trend and the greatest number of hydrogen bond interactio...
The body’s normal immune response against any invading pathogen that causes infection in the body... more The body’s normal immune response against any invading pathogen that causes infection in the body results in inflammation. The sudden transformation in inflammation leads to the rise of inflammatory diseases such as chronic inflammatory bowel disease, autoimmune disorders, and colorectal cancer (different types of cancer develop at the site of chronic infection and inflammation). Inflammation results in two ways: short-term inflammation i.e., non-specific, involves the action of various immune cells; the other results in long-term reactions lasting for months or years. It is specific and causes angiogenesis, fibrosis, tissue destruction, and cancer progression at the site of inflammation. Cancer progression relies on the interaction between the host microenvironment and tumor cells along with the inflammatory responses, fibroblast, and vascular cells. The two pathways that have been identified connecting inflammation and cancer are the extrinsic and intrinsic pathways. Both have the...
Background: We propose a new approach based on genetic distances among viral strains to infer abo... more Background: We propose a new approach based on genetic distances among viral strains to infer about risk exposures and location of transmission at population level. Methods: We re-analysed 133 viral sequences obtained during a cross-sectional survey of 4020 subjects living in a hepatitis C virus (HCV) endemic area in 2002. A permutation test was used to analyze the correlation between matrices of genetic distances in the NS5b region of all pairwise combinations of the 133 viral strains and exposure status (jointly exposed or not) to several potential HCV risk factors. Results: Compared to subjects who did not share the same characteristics or iatrogenic exposures, the median Kimura genetic distances of viral strains were significantly smaller between brothers and sisters (0.031 versus 0.102, P,0.001), mother and child (0.044 versus 0.102, P,0.001), father and child (0.045 versus 0.102, P,0.001), or subjects exposed to periodontal treatment (0.084 versus 0.102, P = 0.02). Conversely, viral strains were more divergent between subjects exposed to blood transfusions (0.216 versus 0.102, P = 0.04) or tooth filling or extraction (0.108, versus 0.097, P = 0.05), suggesting acquisition of the virus outside of the village. Conclusion: This method provided insights on where infection took place (household, village) for several sociodemographic characteristics or iatrogenic procedures, information of great relevance for targeting prevention interventions. This method may have interesting applications for virologists and epidemiologists studying transmission networks in health-care facilities or among intravenous drug users.
Phosphorus Sulfur and Silicon and The Related Elements, Mar 1, 2002
ABSTRACT Some of novel N , N &#39;-bis-(1,2,4-triazin-4-yl)dicarboxylic acid amides ( 2-5 ) a... more ABSTRACT Some of novel N , N &#39;-bis-(1,2,4-triazin-4-yl)dicarboxylic acid amides ( 2-5 ) and thiadiazolo[2,3- b ][1,2,4]triazin-7-yl carboxylic acid derivatives ( 6 , 7 ) were prepared by heating 4-amino-6-methyl-5-oxo-3-thioxo-2,3,4,5-tetrahydro-1,2,4-triazine ( 1 ) with different dicarboxylic acids (oxalic, malonic, fumaric, maleic, succinic, and phthalic acids respectively) in POCl 3 . Refluxing 1 with 1-chloro-2,4-dinitrobenzene in DMF yielded 3-methyl-6-nitro-10 H -benzo[1,2,4]thiadiazino[2,3- c ][1,2,4]triazin-4-one ( 8 ). Condensation of 1 with 2,4-pentandione in refluxing acetic acid furnished 6-methyl-4-(1-methyl-3-oxobut-1-enylamino)-3-thioxo-3,4-dihydro-2 H -[1,2,4]triazin-5-one ( 9 ). 3,8-D imethyl[1,2,4] triazino[3,4- b ][1,3,4]thiadiazine-4,7-dione ( 11 ) was prepared by refluxing 1 with 2-bromopropionyl bromide in anhydrous benzene to afford the corresponding N -acetylated derivative 10 , which was cyclized by using triethylamine. Also, some triazinylquinazolinones 13a , b were obtained by fusion of 1 with 6-bromo(and/or 6,8-dibromo)-2-methyl-3,1-benzoxazin-4 H -ones.
Background and aims: According to the literature, 14-46% of subjects clear hepatitis C virus (HCV... more Background and aims: According to the literature, 14-46% of subjects clear hepatitis C virus (HCV) from blood after infection. Controversy exists about sex differences in HCV clearance rates. Patients and methods: We compared HCV clearance in males and females using data from a large population based study on HCV infection in Egypt. Definitions used in the paper were: cleared HCV infection (positive HCV antibody and negative HCV RNA test results) and chronic HCV infection (positive HCV antibody and positive HCV RNA test results). The study sample included 4720 village residents aged 18-65 years recruited through home based visits (n = 2425) or voluntary screening (n = 2295). Results: Overall, HCV antibody prevalence was 910/4720 (19.3% (95% confidence interval 18.2-20.4)). Of those with HCV antibodies (n = 910), 61.5% had chronic HCV infection. Compared with males, females were more likely to have cleared the virus (44.6% v 33.7%, respectively; p = 0.001). Control for age, schistosomiasis history, iatrogenic exposures, and sexual exposure to HCV did not alter the positive association between female sex and viral clearance. This study provides strong evidence in favour of a higher HCV clearance rate in females compared with males.
HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific re... more HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.
Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Introduction: Oxidative ... more Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Introduction: Oxidative stress plays an important role in hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCC). Glutathione S-transferases (GSTs) prevent oxidative stress associated cellular damage, catalyzing the conjugation of electrophilic compounds with glutathione. Partial or complete deletions of GST theta 1 (GSTT1) and mu 1 (GSTM1) have been associated with chronicity of HCV infection. However, data on the role of these null genotypes in progression to HCC is lacking. We investigated whether GSTT1 and GSTM1 modify the association between HCV and HCC in a case-control study in Egypt. Methods: Participants were recruited at the National Cancer Institute of Cairo University. Cases of HCC were confirmed on pathology, alpha-fetoprotein levels and imaging. Non-cancer controls, representative of the general population with respect to HCV prevalence, were frequency matched to cases on age, sex, and area of residence. HCV antibodies were measured in blood samples by enzyme-linked immunosorbent assay, and HCV RNA was measured by reverse transcription-polymerase chain reaction (RT-PCR). Homozygous deletions in GSTT1 and GSTM1 were determined by separate multiplex PCR methods. For these analyses, participants with active HBV were excluded. Logistic regression was used to analyze the risk of HCC associated with HCV after stratifying by GSTT1 and GSTM1 genotype. Additive interaction of HCV and null GST genotypes in HCC risk were determined by calculating the interaction contrast ratio (ICR). All analyses were adjusted for age, sex, current smoking, alcohol intake, urban/rural status, and pesticide use. Results: Compared to controls, HCC cases were more likely to be older, married, non-smokers, living in rural areas, and exposed to agricultural pesticides. HCV infection was a strong risk factor for HCC in this population [adjusted odds ratio (aOR): 13.6, 95% confidence interval (CI): 9.7-18.9]. GSTT1 and GSTM1 polymorphisms alone were not associated with HCC risk. However, the association of HCV with HCC was markedly stronger in patients with null GSTT1 genotype [aOR (95% CI): 23.9 (12.8-44.9) for null vs. 11.4 (7.6-17.1) for non-null]. The observations were similar for GSTM1 genotype [aOR (95% CI): 17.7 (11.1-28.5) for null vs. 10.0 (6.2-16.1) for non-null]. Additive positive interaction, as determined by an ICR value greater than zero, between HCV and null GSTT1 was significant for HCC risk [ICR (95% CI): 10.9 (2.6-41.9)]. However, the ICR for GSTM1 and HCV interaction was not statistically significant [ICR (95% CI): 2.9 (−1.7-11.1)]. Conclusions: Chronic HCV carriers with null GST genotypes are more likely to have HCC as compared to those with non-null genotypes. Studies are needed to confirm these findings and investigate the exact mechanisms underlying HCC susceptibility associated with the null GST genotypes in chronic HCV patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3752. doi:10.1158/1538-7445.AM2011-3752
Middle East Respiratory Syndrome (MERS) is a viral respiratory disease caused b a special type of... more Middle East Respiratory Syndrome (MERS) is a viral respiratory disease caused b a special type of coronavirus called MERS-CoV. In the search for effective substances against the MERS-CoV main protease, we looked into compounds from brown algae, known for their medicinal benefits. From a set of 1212 such compounds, our computer-based screening highlighted four-CMNPD27819, CMNPD1843, CMNPD4184, and CMNPD3156. These showed good potential in how they might attach to the MERS-CoV protease, comparable to a known inhibitor. We confirmed these results with multiple computer tests. Studies on the dynamics and steadiness of these compounds with the MERS-CoV protease were performed using molecular dynamics (MD) simulations. Metrics like RMSD and RMSF showed their stability. We also studied how these compounds and the protease interact in detail. An analysis technique, PCA, showed changes in atomic positions over time. Overall, our computer studies suggest brown algae compounds could be valuable in fighting MERS. However, experimental validation is needed to prove their real-world effectiveness.
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Background and Aim-Retrospective evaluation of hepatitis C virus (HCV) prevalence in lymphoma tis... more Background and Aim-Retrospective evaluation of hepatitis C virus (HCV) prevalence in lymphoma tissues has important applications in clarifying the contribution of viral factors to the pathogenesis. Trials for detection of HCV at the cellular level in lymphoma tissues are, so far, minimal with unsatisfactory results. We aimed to study the detection and localization of HCV in the tissues of B-cell non-Hodgkin lymphoma (NHL) patients. Design-We performed immunohistochemistry to detect the HCV nonstructural 3 protein in paraffin-embedded tissue specimens of B-cell NHL patients, in 39 serum HCV-RNA positive samples and 35 serum HCV-RNA negative samples as controls. The serum analysis was carried out for HCV antibodies using enzyme-linked immunoassay and for HCV-RNA using reverse transcription-polymerase chain reaction. Reverse transcription-polymerase chain reaction was used to detect the HCV-RNA in tissues in immunohistochemically positive cases. We correlated the results with the clinicopathologic characteristics of the patients. Results-A diffuse cytoplasmic immunohistochemical staining for HCV in the lymphoid cells was detected in 8 of 39 serum positive cases (20.5%), all of which were genotype 4, which is the most prevalent HCV genotype in Egypt. Only 2 out of 35 serum negative control samples showed positive staining and in 1 of them HCV-RNA was detected in tissue. No significant correlation was detected between HCV positive cases and the clinicopathologic features of the patients. Conclusions-Immunohistochemical detection of HCV proteins in lymphoma tissues supports a potential role of viral replication in lymphomagenesis. The low number of cases showing expression of viral proteins may represent a low viral load in lymphoid tissue and/or restriction of HCV protein expression to certain subtypes of B-cell NHL. Immunohistochemistry can be used as
Background and Aims: Neutrophils are the most abundant circulating leukocytes in humans. Recently... more Background and Aims: Neutrophils are the most abundant circulating leukocytes in humans. Recently, dual roles of tumorassociated neutrophils (TANs) within the multiple step paradigm of cancer have been recognized. Although there is the evidence for the existence of N1 (antitumoral) and N2 (protumoral) TANs, similar as M1 and M2 macrophage polarization, it also need to clarify neutrophil effector molecules, such as phenotypic molecular markers, which will contribute to further insights and will be crucial for therapeutical applications in cancer pathologies. Methods: Peripheral blood and intratumor neutrophils from 110 HCC patients assessed by flow cytometry. Immunocytochemistry were used to analyze the distribution and clinical relevance of neutrophils in 192 HCC patients. For functional analysis, human neutrophils are separated from by flow cytometry sorting and then co-cultured with CD4+/CD8+ effector T cells and tumor-specific antigen inducing CTLs for 48 h in vitro. Finally, in vivo analysis, the frequencies and function of neutrophils in peripheral blood. spleen and tumor are evaluated by flow cytometry. Results: We show here that the expression of programmed death ligand 1(PD-L1), which interacts with PD-1, is increased in neutrophils from HCC patients compared with healthy controls and chronic hepatitis B patients. The expression of PD-L1 was significantly up-regulated on neutrophils after exposure to tumor supernatant from hepatoma cells, and IL-1, IL-6, TNF-aand TGF-bis largely responsible for this up-regulation of PD-L1. Tumor environmental factors induce early transient expression of PD-L1 on neutrophils in tumor bearing mice. The PD-L1+ neutrophils effectively suppressed the proliferation of CD4+/CD8+ effector T cells and tumor-specific T cell immunity, the effect could be reversed by blocking PD-L1 on those neutrophils in vitro. Tumorbearing increased the frequencies of neutrophils in peripheral blood (mainly G2 population), bone marrow (mainly G3 population), and spleen (mainly G1 population). The infiltrating neutrophils in tumor showed high expression of PD-L1 and infiltrating CD3+ T cells showed high expression of PD-1, compared with peripheral blood and spleen in tumor-bearing mice. Conclusions: These data suggest that polarized neutrophils in peripheral blood and intratumor of hepatocellular carcinoma with the high expression of PD-L1 may contribute to maintenance of immunosuppression and foster immune privilege.
Monkeypox viral infection is an emerging threat and a major concern for the human population. The... more Monkeypox viral infection is an emerging threat and a major concern for the human population. The lack of drug molecules to treat this disease may worsen the problem. Identifying potential drug targets can significantly improve the process of developing potent drug molecules for treating monkeypox. The proteins responsible for viral replication are attractive drug targets. Identifying potential inhibitors from known drug molecules that target these proteins can be key to finding a cure for monkeypox. In this work, two viral proteins, DNA-dependent RNA polymerase (DdRp) and viral core cysteine proteinase, were considered as potential drug targets. Sixteen antibiotic drugs from the tetracycline class were screened against both viral proteins through high-throughput virtual screening. These tetracycline class of antibiotic drugs have the ability to inhibit bacterial protein synthesis, which makes these antibiotics drugs a prominent candidate for drug repurposing. Based on the screening...
The Ebola virus and its close relative, the Marburg virus, both belong to the family Filoviridae ... more The Ebola virus and its close relative, the Marburg virus, both belong to the family Filoviridae and are highly hazardous and contagious viruses. With a mortality rate ranging from 23% to 90%, depending on the specific outbreak, the development of effective antiviral interventions is crucial for reducing fatalities and mitigating the impact of Marburg virus outbreaks. In this investigation, a virtual screening approach was employed to evaluate 2042 natural compounds for their potential interactions with the VP35 protein of the Marburg virus. Average and worst binding energies were calculated for all 20 poses, and compounds that exhibited binding energies <−6 kcal/mol in both criteria were selected for further analysis. Based on binding energies, only six compounds (Estradiol benzoate, INVEGA (paliperidone), Isosilybin, Protopanaxadiol, Permethrin, and Bufalin) were selected for subsequent investigations, focusing on interaction analysis. Among these selected compounds, Estradiol ...
The World Health Organization (WHO) has designated the Zika virus (ZIKV) as a significant risk to... more The World Health Organization (WHO) has designated the Zika virus (ZIKV) as a significant risk to the general public’s health. Currently, there are no vaccinations or medications available to treat or prevent infection with the Zika virus. Thus, it is urgently required to develop a highly efficient therapeutic molecule. In the presented study, a computationally intensive search was carried out to identify potent compounds that have the potential to bind and block the activity of ZIKV NS5 RNA-dependent RNA polymerase (RdRp). The anti-dengue chemical library was subjected to high-throughput virtual screening and MM/GBSA analysis in order to rate the potential candidates. The top three compounds were then chosen. According to the MM/GBSA analysis, compound 127042987 from the database had the highest binding affinity to the protein with a minimum binding free energy of −77.16 kcal/mole. Compound 127042987 had the most stable RMSD trend and the greatest number of hydrogen bond interactio...
The body’s normal immune response against any invading pathogen that causes infection in the body... more The body’s normal immune response against any invading pathogen that causes infection in the body results in inflammation. The sudden transformation in inflammation leads to the rise of inflammatory diseases such as chronic inflammatory bowel disease, autoimmune disorders, and colorectal cancer (different types of cancer develop at the site of chronic infection and inflammation). Inflammation results in two ways: short-term inflammation i.e., non-specific, involves the action of various immune cells; the other results in long-term reactions lasting for months or years. It is specific and causes angiogenesis, fibrosis, tissue destruction, and cancer progression at the site of inflammation. Cancer progression relies on the interaction between the host microenvironment and tumor cells along with the inflammatory responses, fibroblast, and vascular cells. The two pathways that have been identified connecting inflammation and cancer are the extrinsic and intrinsic pathways. Both have the...
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Papers by Mai Eldaly