Publications by authors named "Douaa Sayed"

52 Publications

Altered Regulatory B Cell Subsets in Children with Type 1 Diabetes Mellitus.

J Immunol Res 2020 21;2020:8935694. Epub 2020 Jul 21.

Department of Pediatrics, Faculty of Medicine, Assiut University, Egypt.

B regulatory cells (Breg) refer to characteristic subsets of B cells that generally exert anti-inflammatory functions and maintain peripheral tolerance mainly through their ability to secrete interleukin-10 (IL10). Dysregulation in the function of Breg cells was reported in several autoimmune diseases. However, the relation between Breg and children with type 1 diabetes (T1D) is poorly understood. Thus, this study is aimed at determining whether Breg cells play a role in T1D in children or not, so we hypothesized that an altered phenotype of B cell subsets is associated with T1D in children. Children with T1D ( = 29) and control children with normal blood glucose levels ( = 14) were recruited. The percentages of different circulating IL10-producing Breg subsets, including B10, immature transitional, and plasmablasts were determined using flow cytometry analysis. Furthermore, the association between different IL10-producing B cells and patient parameters was investigated. The percentage of circulating IL10CD24CD27 (B10) and IL10CD24CD38 (immature transitional) subsets of Breg cells was significantly lower in T1D patients than in healthy controls. Moreover, these cells were also negatively correlated with fasting blood glucose and HbA1c levels. Breg cells did not correlate with autoantibody levels in the serum. These findings suggest that certain Breg subsets are numerically deficient in children with T1D. This alteration in frequency is associated with deficient islet function and glycemia. These findings suggest that Breg cells may be involved in the loss of auto-tolerance and consequent destruction of pancreatic cells and could, therefore, be a potential target for immunotherapy.
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http://dx.doi.org/10.1155/2020/8935694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7391103PMC
July 2020

Revisiting the management of chronic ITP; a randomized controlled clinical trial.

Platelets 2020 Mar 9:1-7. Epub 2020 Mar 9.

Department of Internal Medicine, Clinical Hematology Unit, Faculty of Medicine, Assiut University, Assiut, Egypt.

The balance between therapy effectiveness and economic efficiency in chronic immune thrombocytopenia (ITP) becomes more confusing. This single-center open label randomized controlled trial evaluates the effectiveness and safety of hydroxychloroquine in chronic ITP patients against other affordable second-line treatments. It is registered under number (NCT03229746) at Clinical Trials.gov. 120 patients were recruited and randomly allocated to three arms of hydroxychloroquine, vincristine, and azathioprine equally. Platelet counts of more than 100 × 10/L were interpreted as complete response (CR), while response (R) was determined as platelet counts ranging from 30 × 10/L to less than 100 × 10/L with the doubling of the pretreatment platelet count. Overall response (OR) was defined to include both CR and R. Patients were monitored every 6 weeks for a total of 24 weeks. The population baseline characteristics regarding age, sex, duration of the disease, baseline platelets count, and presence of antinuclear antibodies ANA or antiplatelet antibodies were similar among tested groups. There was a significant difference in the overall response between hydroxychloroquine (80.6%) and azathioprine (55.9%) (-value <0.05). This difference was not significant between hydroxychloroquine and vincristine group (63.2%) (-value = 0.09). This study proves that hydroxychloroquine can contribute to the therapy of chronic ITP especially as an affordable and well-tolerated drug.
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http://dx.doi.org/10.1080/09537104.2020.1738367DOI Listing
March 2020

Synthesis of a novel series of (Z)-3,5-disubstituted thiazolidine-2,4-diones as promising anti-breast cancer agents.

Bioorg Chem 2020 03 15;96:103569. Epub 2020 Jan 15.

Department of Clinical Pathology, South Egypt Cancer Institute, Assiut University, Assiut 71516, Egypt.

A novel series of (Z)-3,5-disubstituted thiazolidine-2,4-diones 4-16 has been designed and synthesized. Preliminary screening of these compounds for their anti-breast cancer activity revealed that compounds 5, 7, and 9 possess the highest anti-cancer activities. The anti-tumor effects of compounds 5, 7, and 9 were evaluated against human breast cancer cell lines (MCF-7 and MDA-MB-231) and human breast cancer cells. They were also evaluated against normal non-cancerous breast cells, isolated from the same patients, to conclude about their use in a potential targeted therapy. Using MTT uptake method, these three compounds 5, 7, and 9 blunt the proliferation of these cancer cells in a dose-dependent manner with an IC of 1.27, 1.50 and 1.31 µM respectively. Interestingly, using flow cytometry analysis these three compounds significantly mediated apoptosis of human breast cancer cells without affecting the survival of normal non-cancerous breast cells that were isolated from the same patients. Mechanistically, these compounds blunt the proliferation of MCF-7 breast cancer cells by robustly decreasing the phosphorylation of AKT, mTOR and the expression of VEGF and HIF-1α. Most importantly, compounds 5, 7, and 9 without affecting the phosphorylation and expression of these crucial cellular factors in normal non-cancerous breast cells that were isolated from the same patients. Additionally, using Western blot analysis the three compounds significantly (P < 0.05) decreased the expression of the anti-apoptotic Bcl-2 members (Bcl-2, Bcl- and Mcl-1) and increased the expression of the pro-apoptotic Bcl-2 members (Bak, Bax and Bim) in MCF-7, MDA-MB-231 and human breast cancer cells making these breast cancer cells susceptible for apoptosis induction. Taken together, these data provide great evidences for the inhibitory activity of these compounds against breast cancer cells without affecting the normal breast cells.
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http://dx.doi.org/10.1016/j.bioorg.2020.103569DOI Listing
March 2020

Hepatitis C Virus Affects Tuberculosis-Specific T Cells in HIV-Negative Patients.

Viruses 2020 01 15;12(1). Epub 2020 Jan 15.

Department of Clinical Pathology, Faculty of Medicine, Sohag University, Sohag 82524, Egypt.

The occurrence of tuberculosis (TB) and hepatitis C virus (HCV) infections in the same patient presents a unique clinical challenge. The impact of HCV infection on the immune response to TB remains poorly investigated in TB/HCV patients. This study was conducted to evaluate the impact of HCV on the T-cell-mediated immune response to TB in coinfected patients. Sixty-four patients with active TB infections were screened for coinfection with HCV. The expression of immune activation markers IFN-γ, CD38, and HLA-DR on TB-specific CD4 T cells was evaluated by flow cytometry in TB-monoinfected patients, TB/HCV-coinfected patients, and healthy controls. IL-2, IL-4, IFN-γ, TNF-α, and IL-10 levels were measured using ELISA. The end-of-treatment response to anti-TB therapy was recorded for both patient groups. Significantly lower levels of CD4IFN-γCD38 and CD4IFN-γHLA-DR T cells were detected in TB/HCV-coinfected patients compared to TB monoinfected patients and controls. TB/HCV-coinfected patients showed higher serum levels of IL-10. The baseline frequencies of TB-specific activated T-cell subsets did not predict the response to antituberculous therapy in TB/HCV patients. We concluded that different subsets of TB-specific CD4 T cells in TB/HCV-infected individuals are partially impaired in early-stage HCV infection. This was combined with increased serum IL-10 level. Such immune modulations may represent a powerful risk factor for disease progression in patients with HCV/TB coinfection.
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http://dx.doi.org/10.3390/v12010101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019953PMC
January 2020

Periostin expression and characters of human adipose tissue-derived mesenchymal stromal cells were aberrantly affected by cultivation.

Stem Cell Investig 2019 23;6:33. Epub 2019 Sep 23.

Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.

Background: Human adipose tissue-derived mesenchymal stromal cells (AD-MSCs) have been under focus in regenerative medicine since their discovery as a suitable source of MSCs. AD-MSCs are heterogeneous cells and exhibit variations in population doubling time, morphology and proliferative capacity. This study investigated if human AD-MSCs are developing, during long-term cultivation, in an unwanted or aberrant way.

Methods: This study monitored AD-MSCs during their culture till the tenth passage investigating proliferation kinetics, DNA index and surface markers expression. Also, periostin gene expression was examined.

Results: The proliferation capacity and colony forming unit were decreased after passage 6 and the population doubling time was increased. Flow cytometric analysis revealed that newly cultivated population strongly expressed MSCs markers, furthermore, reduction of CD105 expression appeared in passage 5 onwards, the later was associated with significant increase in expression of CD34 (a hematopoietic cell marker). Also, reduction of CD73 and CD90 expression was observed from passage 8. Furthermore, during the first six passages, periostin expression was significantly unchanged, with significant upregulation in late passages.

Conclusions: Long-term cultivation of human AD-MSCs changed their characters in an aberrant way and the first four passages might be the most appropriate passages for therapy. More investigation and understanding of these variations are needed to help in standardizing the expansion of MSCs-based therapies.
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http://dx.doi.org/10.21037/sci.2019.08.09DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6789196PMC
September 2019

What Egyptians think. Knowledge, attitude, and opinions of Egyptian patients towards biobanking issues.

BMC Med Ethics 2019 08 9;20(1):57. Epub 2019 Aug 9.

Research Department, Children's Cancer Hospital Egypt, 57357, Cairo, Egypt.

Background: Biobanking is a relatively new concept in Egypt. Building a good relationship with different stakeholders is essential for the social sustainability of biobanks. To establish this relationship, it is necessary to assess the attitude of different groups towards this concept. The objective of this work is to assess the knowledge, attitude, and opinions of Egyptian patients towards biobanking issues.

Methods: We designed a structured survey to be administered to patients coming to the outpatient clinics in 3 university hospitals in Egypt. The survey included questions estimating the level of knowledge about the term "Biobank", together with questions about the attitudes and opinions about related issues.

Results: Two hundred and fifty-nine patients participated in the survey. Eighty-one percent of participants reported that they never heard about the term before. About 85% expressed that they would be willing to donate their samples for research and about 87% thought that sample donation did not contradict their religious beliefs. Fifty eight percent were willing to participate in a genetic research project, 27.8% supported sharing their sample with pharmaceutical companies, and 32.4% agreed to share their samples with institutions abroad.

Conclusion: Although there is limited knowledge about biobanking among Egyptian patients, many had a positive attitude towards sample donation and didn't show religious concerns against it. However, they showed concerns regarding participation in genetic research and with sharing their samples across borders or with pharmaceutical companies. Public education about biobanking is possible, taking into consideration the specific cultural and legal framework in Egypt.
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http://dx.doi.org/10.1186/s12910-019-0394-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6689171PMC
August 2019

Enhanced susceptibility to apoptosis and growth arrest of human breast carcinoma cells treated with silica nanoparticles loaded with monohydroxy flavone compounds.

Biochem Cell Biol 2019 10 14;97(5):513-525. Epub 2019 Jan 14.

Department of Chemistry, Faculty of Science, Assiut University, Assiut 71516, Egypt.

The treatment of drug-resistant cancer is a clinical challenge, hence screening for novel anticancer drugs is critically important. In this study, we investigated the anti-tumor potential of three plant-derived flavone compounds: 3-hydroxy flavone (3-HF), 6-hydroxy flavone (6-HF), and 7-hydroxy flavone (7-HF), either alone or combined with silica nanoparticles (3-HF + NP, 6-HF + NP, and 7-HF + NP), on the human breast carcinoma cell lines MDA-MB-231 and MCF-7, as well as on non-tumorigenic normal breast epithelial cells (MCF-10). The IC values of these flavone compounds loaded with NP (flavones + NP) in these cell lines were determined to be 1.5 μg/mL without affecting the viability of normal MCF-10 cells. Additionally, using annexin V - propidium iodide double-staining followed by flow cytometry analysis, we found that the combination of flavones with NP significantly induced apoptosis in MCF-7 and MDA-MB-231 cancer cells. Furthermore, flavones + NP increased the expression of cytochrome and caspase-9, mediating the growth arrest of these cancer cells. Most importantly, the combination of flavones with NP significantly abolished the expression of ATF-3, which is responsible for the proliferation and invasion of bone-metastatic breast cancer cells. Our data revealed the potential therapeutic effects of these flavones in fighting breast cancer cells, and provide the first insights concerning the underlying molecular mechanisms.
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http://dx.doi.org/10.1139/bcb-2018-0133DOI Listing
October 2019

Relation of Regulatory Foxp3+ T Cells with Helicobacter pylori and Its Virulence Genes.

Egypt J Immunol 2018 Jan;25(1):9-17

Department of Medical Microbiology & Immunology, Faculty of Medicine, Assiut University, Assiut, Egypt.

The study aimed to assess the tangled relation between various CD25 subsets (positive, negative and high) of CD4+ FoxP3+ T cells and H. pylori including its virulence genes (CagA and VacA). Diagnosis of H. pylori and its virulence genes was based on a positive culture, histopathology and/or CLO-test and PCR. Flow cytometry was used toquantifyTregs.CD4+CD25high Foxp3+ T cells were higher in patients than controls and somewhat more in H. pylori positive than negative patients. CD4+CD25high Foxp3+ T cells secreting IL10 were lower in H. pylori positive patients.CD4+CD25-Fox3+T cells were also higher in patients than controls and more in those negative for H. pylori. Moderate negative correlation was found between the presence of CagA or VacA sm genotypes and Tregs secreting IL10. CD4+CD25- Foxp3+ T cells, especially those secreting IL10, tend to be higher in patients carrying VacA m1 allele than m2 allele. In conclusion, H. pylori stimulate a regulatory T cell response, probably contributing to gastric diseases. CD25 negative subset of Fox3+CD4+T cells needs further studying to declare its potential role in immunopathogenesis of gastric diseases. Tregs are positively associated with vacA alleles.
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January 2018

Author Correction: Strong associations between chromosomal aberrations in blood lymphocytes and the risk of urothelial and squamous cell carcinoma of the bladder.

Sci Rep 2018 May 22;8(1):8183. Epub 2018 May 22.

Department of Biostatistics, Bioinformatics, and Biomathematics, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington DC, USA.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
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http://dx.doi.org/10.1038/s41598-018-26488-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5962601PMC
May 2018

Fluorouracil-Loaded Gold Nanoparticles for the Treatment of Skin Cancer: Development, in Vitro Characterization, and in Vivo Evaluation in a Mouse Skin Cancer Xenograft Model.

Mol Pharm 2018 06 7;15(6):2194-2205. Epub 2018 May 7.

Department of Pharmaceutics, Faculty of Pharmacy , Assiut University , Assiut 71526 , Egypt.

Fluorouracil (5-FU) is an antimetabolite drug used in the treatment of various malignancies, such as colon and skin cancers. However, its systemic administration results in severe side effects. Topical 5-FU delivery for the treatment of skin cancer could circumvent these shortcomings, but it is limited by the drug poor permeability through the skin. To enhance 5-FU efficacy against skin cancer and reduce its systemic side effects, it was loaded into a gold nanoparticle (GNP)-based topical delivery system. 5-FU was loaded onto GNPs capped with CTAB through ionic interactions between 5-FU and CTAB. GNPs were prepared at different 5-FU/CTAB molar ratios and evaluated using different techniques. GNP stability and drug release were studied as a function of salt concentration and solution pH. Optimum 5-FU/CTAB-GNPs were incorporated into gel and cream bases, and their ex vivo permeability was evaluated in mice dorsal skin. The in vivo anticancer efficacy of the same preparations was evaluated in A431 tumor-bearing mice. The GNPs had spherical shape and a size of ∼16-150 nm. Maximum 5-FU entrapment was achieved at 5-FU/CTAB molar ratio of 1:1 and pH 11.5. Drug release from GNPs was sustained and pH-dependent. 5-FU GNP gel and cream had around 2-fold higher permeability through mice skin compared with free 5-FU gel and cream formulations. Further, in vivo studies in a mouse model having A431 skin cancer cells implanted in the subcutaneous space showed that the GNP gel and cream achieved 6.8- and 18.4-fold lower tumor volume compared with the untreated control, respectively. These results confirm the potential of topical 5-FU/CTAB-GNPs to enhance drug efficacy against skin cancer.
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http://dx.doi.org/10.1021/acs.molpharmaceut.8b00047DOI Listing
June 2018

Strong associations between chromosomal aberrations in blood lymphocytes and the risk of urothelial and squamous cell carcinoma of the bladder.

Sci Rep 2017 10 18;7(1):13493. Epub 2017 Oct 18.

Department of Biostatistics, Bioinformatics, and Biomathematics, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington DC, USA.

Chromosomal aberrations (CAs) in blood lymphocytes have been shown to be associated with overall cancer risk and aging. However, their relationship to bladder cancer risk remains to be elucidated. In a case-control study of bladder cancer in Egypt, we examined the relationship between the increased frequency of CAs in blood lymphocytes and bladder cancer risk. High frequency of CAs was significantly associated with an increased risk of bladder cancer [adjusted odds ratios (OR) = 3.90, 95% confidence interval (CI) = 2.65-5.73]. The associations were somewhat stronger in squamous cell carcinomas (SCC, OR = 4.90) than in urothelial carcinomas (UC, OR = 3.62). We also identified chromosome specific CAs for chromosomes 3, 4, 5, 8, 9, 10, 11, 12, 17, 19 that were significantly associated with an increased risk of bladder cancer. We observed particularly strong associations between aberrations of chromosomes 12, 13, 17 and risk of SCC (OR = 7.06, 6.91 and 6.23, respectively).

Conclusion: increased frequency of chromosomal aberrations in blood lymphocytes was significantly associated with bladder cancer risk. Overall and chromosome specific aberrations in blood lymphocytes may be a unique set of biomarkers for risk assessments of SCC and UC.
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http://dx.doi.org/10.1038/s41598-017-13976-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5647374PMC
October 2017

Outcome and Clinical Significance of Immunophenotypic Markers Expressed in Different Treatment Protocols of Pediatric Patients With T-ALL in Developing Countries.

Clin Lymphoma Myeloma Leuk 2017 07 10;17(7):443-449. Epub 2017 May 10.

Laboratory Department, King Fahad Specialist Hospital, Dammam, Kingdom of Saudi Arabia.

Background: T-cell acute lymphoblastic leukemia (T-ALL) accounts for about 15% of pediatric ALL. With wider use of intensive chemotherapy, the prognosis for childhood T-ALL has improved. Further gains in treatment outcome will likely require methods to identify patients who continue to fail on contemporary protocols. This study aimed to evaluate pediatric patients with T-ALL at 2 different Arabic cancer centers regarding their clinicopathologic, immunophenotypic, and cytogenetic features and outcome.

Patients And Methods: This retrospective study included all children with T-ALL treated between 2003 and 2013 at 2 oncology centers in the Middle East. Patients were divided into (group I) treated with Berlin-Frankfurt-Münster (BFM)-90 treatment protocol between February 2003 and June 2007 and (group II) includes all patients treated thereafter by the Total Therapy Study XIII protocol for high-risk ALL.

Results: This study included 103 patients with a median age of 8.9 years. The male to female ratio was 2.6:1. The median initial white blood cell count was 123 × 10/L. Central nervous system leukemia was detected in 15%. The early T-cell precursor (ETP)-ALL phenotype was found in 16.5%. The 5-year overall survival was 20.7% ± 67.5% and 72.9% ± 5.7% (P < .01); the 5-year disease-free survival was 47.1% ± 13.8% and 77.3% ± 6.0% (P = .023); and the 5-year event-free survival was 28.6% ± 12.1% and 71.1% ± 6.2% (P = .003) for group I and II, respectively.

Conclusion: The outcome of patients with T-ALL significantly improved in patients who received the treatment protocol of ALL with high-risk criteria. This protocol eliminates the bad outcomes effect of several clinical and immunophenotypic markers. Patient with the ETP-ALL phenotype had a nonsignificant inferior outcome compared with the non-ETP-ALL group.
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http://dx.doi.org/10.1016/j.clml.2017.05.012DOI Listing
July 2017

Non-neoplastic Portal Vein Thrombosis in HCV Cirrhosis Patients: Is it an Immuno-Inflammatory Disorder?

Ann Hepatol 2017 Jul-Aug;16(4):574-583

Department of Internal Medicine, School of Medicine, Minia University, Minia, Egypt.

Background And Aims: Portal vein thrombosis (PVT) is a critical complication in cirrhotic patients. We explored the role of the activated factor VII-antithrombin (FVIIa-AT) complex and enhanced monocytic tissue factor (TF) expression in the development and prediction of non-neoplastic PVT in cirrhotic patients.

Material And Methods: A total of 30 HCV-cirrhosis patients were included in our study. They were compared to 35 cirrhotic patients without PVT, 15 non-cirrhotic patients with PVT, and 15 healthy controls. The plasma level of the FVIIa-AT complexes was analyzed by ELISA. MIF CD142, CD86, and HLA-DR on monocytes (CD14) were determined by flow cytometry.

Results: Compared with cirrhotic patients without PVT, cirrhotic patients with PVT had comparable plasma values of FVIIa, AT, and the FVIIa-AT complex. However, they had significantly lower values compared to non-cirrhotic patients with PVT and healthy controls. Cirrhotic patients with PVT had increased monocytic TF expression (MIF CD142) compared to non-PVT cirrhotic patients and healthy controls [86.5 (93.5) vs. 18 (32.0) and 11.0 (6.0), respectively; p < 0.001 for each]. However, cirrhosis PVT could not be distinguished from non-cirrhosis PVT. The area under the ROC curve of MIF CD142 was 0.759 (0.641- 0.876; p = 0.000) at an optimal cut-off value of 45, which yielded a sensitivity of 60% and a specificity of 77.1%, as well as a PPV and NPV of 69.2% for each.

Conclusion: Enhanced expression of monocytic TF may have a role in the development and prediction of non-neoplastic PVT in HCV-cirrhosis patients. Large multicenter studies are necessary to validate our results.
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http://dx.doi.org/10.5604/01.3001.0010.0296DOI Listing
April 2018

Gold nanoparticles capped with benzalkonium chloride and poly (ethylene imine) for enhanced loading and skin permeability of 5-fluorouracil.

Drug Dev Ind Pharm 2017 Nov 21;43(11):1780-1791. Epub 2017 Jun 21.

a Department of Pharmaceutics, Faculty of Pharmacy , Assiut University , Assiut , Egypt.

Objective: To enhance 5-fluorouracil (5-FU) permeability through the skin by loading onto gold nanoparticles (GNPs) capped with two cationic ligands, benzalkonium chloride (BC) or poly (ethylene imine) (PEI). Whereas 5-FU has excellent efficacy against many cancers, its poor permeability through biological membranes and several adverse effects limit its clinical benefits. BC and PEI were selected to stabilize GNPs and to load 5-FU through ionic interactions.

Methods: 5-FU/BC-GNPs and 5-FU/PEI-GNPs were prepared at different 5-FU/ligand molar ratios and different pH values and were evaluated using different techniques. GNPs stability was tested as a function of salt concentration and storage time. 5-FU release from BC- and PEI-GNPs was evaluated as a function of solution pH. Ex vivo permeability studies of different 5-FU preparations were carried out using mice skin.

Results: 5-FU-loaded GNPs size and surface charge were dependent on the 5-FU/ligand molar ratios. 5-FU entrapment efficiency and loading capacity were dependent on the used ligand, 5-FU/ligand molar ratio and solution pH. Maximum drug entrapment efficiency of 59.0 ± 1.7% and 46.0 ± 1.1% were obtained for 5-FU/BC-GNPs and 5-FU/PEI-GNPs, respectively. 5-FU-loaded GNPs had good stability against salinity and after storage for 4 months at room temperature and at 4 °C. In vitro 5-FU release was pH- and ligand-dependent where slower release was observed at higher pH and for 5-FU/BC-GNPs. 5-FU permeability through mice skin was significantly higher for drug-loaded GNPs compared with drug-ligand complex or drug aqueous solution.

Conclusion: Based on these results, BC- and PEI-GNPs might find applications as effective topical delivery systems of 5-FU.
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http://dx.doi.org/10.1080/03639045.2017.1339082DOI Listing
November 2017

Characteristics of escape mutations from occult hepatitis B virus infected patients with hematological malignancies in South Egypt.

World J Hepatol 2017 Mar;9(9):477-486

Abeer Elkady, Department of Clinical and Chemical Pathology, Medical School of South Valley University, Qena 83523, Egypt.

Aim: To investigate the prevalence and virological characteristics of occult hepatitis B virus (HBV) infections in patients with hematological malignancies in South Egypt.

Methods: Serum samples were collected from 165 patients with hematological malignancies to monitor titers of HBV DNA, hepatitis B surface antigen (HBsAg), and antibodies to HBV core (anti-HBc) and surface antigens. Serum samples negative for HBsAg and positive for anti-HBc were subjected to nucleic acid extraction and HBV DNA detection by real-time polymerase chain reaction. DNA sequences spanning the S region were analyzed in cases with occult HBV infection. comparative study of constructed 1.24-fold wild type and S protein mutant HBV genotype D clones was further performed.

Results: HBV DNA was detected in 23 (42.6%) of 54 patients with hematological malignancies who were HBsAg negative, but anti-HBc positive, suggesting the presence of occult HBV infection. The complete HBV genome was retrieved from 6 occult HBV patients, and P120T and S143L were detected in 3 and 2 cases, respectively. Site directed mutagenesis was done to produce 1.24-fold genotype D clones with amino acid mutations T120 and L143. The analyses revealed that a lower level of extracellular HBsAg was detected by chemiluminescence enzyme immunoassay (CLEIA) with the clone containing T120 mutation, compared with the wild type or the clone with S143L mutation despite the similar levels of extracellular and intracellular HBsAg detected by Western blot. Southern blot experiments showed that the levels of intracellular HBV DNA were not different between these clones.

Conclusion: Occult HBV infection is common in patients with hematological malignancies and associated with P120T and S143L mutations. 120T mutation impairs the detection of HBsAg by CLEIA.
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http://dx.doi.org/10.4254/wjh.v9.i9.477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5368625PMC
March 2017

Virulence of geographically different Cryptosporidium parvum isolates in experimental animal model

Ann Parasitol 2016 10 1;62(3):221-32. Epub 2016 Oct 1.

Department of Parasitology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt

Cryptosporidium parvum is a coccidian parasite which causes gastrointestinal disease in humans and a variety of other mammalian species. Several studies have reported different degrees of pathogenicity and virulence among Cryptosporidium species and isolates of the same species as well as evidence of variation in host susceptibility to infection. The study aimed to investigate infectivity and virulence of two Cryptosporidium parvum “Iowa isolate” (CpI) and a “local water isolate” (CpW). Thirty-three Swiss albino mice have been divided into three groups: Negative control Group (C), the CpI group infected with “Iowa isolate “and the CpW group infected with C. parvum oocysts isolated from a local water supply. Infectivity and virulence have been measured by evaluating clinical, parasitological and histological aspects of infection. Significant differences were detected regarding oocysts shedding rate, clinical outcomes, and the histopathological picture of the intestine, lung, and brain. It was concluded that the local water isolate is significantly more virulent than the exported one.
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http://dx.doi.org/10.17420/ap6203.56DOI Listing
October 2016

Gold nanoparticles enhance 5-fluorouracil anticancer efficacy against colorectal cancer cells.

Int J Pharm 2016 Nov 29;513(1-2):648-658. Epub 2016 Sep 29.

Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt.

5-Fluorouracil (5-FU), an antimetabolite drug, is extensively used in the treatment solid tumors. However, its severe side effects limit its clinical benefits. To enhance 5-FU anticancer efficacy and reduce its side effects it was loaded onto gold nanoparticles (GNPs) using two thiol containing ligands, thioglycolic acid (TGA) and glutathione (GSH). The GNPs were prepared at different 5-FU/ligand molar ratios and evaluated using different techniques. Anticancer efficacy of 5-FU/GSH-GNPs was studied using flow cytometry in cancerous tissue obtained from patients having colorectal cancer. The GNPs were spherical in shape and had a size of ∼9-17nm. Stability of the GNPs and drug release were studied as a function of salt concentration and solution pH. Maximum 5-FU loading was achieved at 5-FU/ligand molar ratio of 1:1 and 2:1 for TGA-GNPs and GSH-GNPs, respectively. GNPs coating with pluronic F127 improved their stability against salinity. 5-FU release from GNPs was slow and pH-dependent. 5-FU/GSH-GNPs induced apoptosis and stopped the cell cycle progression in colorectal cancer cells. They also had a 2-fold higher anticancer effect compared with free 5-FU. These results confirm the potential of GNPs to enhance 5-FU anticancer efficacy.
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http://dx.doi.org/10.1016/j.ijpharm.2016.09.076DOI Listing
November 2016

Synthesis, Structural Characterization, and Preclinical Efficacy of a Novel Paclitaxel-Loaded Alginate Nanoparticle for Breast Cancer Treatment.

Int J Breast Cancer 2016 30;2016:7549372. Epub 2016 Aug 30.

The Vontz Center for Molecular Studies, University of Cincinnati College of Medicine, Cincinnati, OH, USA; University of Cincinnati Cancer Institute, Cincinnati, OH, USA.

Purpose. The antitumor activity of a novel alginate (ALG) polymer-based particle that contained paclitaxel (PTX) was evaluated using human primary breast cancer cells. Materials and Methods. PTX was combined with ALG in a nanoparticle as a drug delivery system designed to improve breast cancer tumor cell killing. PTX-ALG nanoparticles were first synthesized by nanoemulsification polymer cross-linking methods that improved the aqueous solubility. Structural and biophysical properties of the PTX-ALG nanoparticles were then determined by transmission electron microscopy (TEM) and high performance liquid chromatography (HPLC) fluorescence. The effect on cell cycle progression and apoptosis was determined using flow cytometry. Results. PTX-ALG nanoparticles were prepared and characterized by ultraviolet (UV)/visible (VIS), HPLC fluorescence, and TEM. PTX-ALG nanoparticles demonstrated increased hydrophobicity and solubility over PTX alone. Synthetically engineered PTX-ALG nanoparticles promoted cell-cycle arrest, reduced viability, and induced apoptosis in human primary patient breast cancer cells superior to those of PTX alone. Conclusion. Taken together, our results demonstrate that PTX-ALG nanoparticles represent an innovative, nanoscale delivery system for the administration of anticancer agents that may avoid the adverse toxicities with enhanced antitumor effects to improve the treatment of breast cancer patients.
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http://dx.doi.org/10.1155/2016/7549372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5021896PMC
September 2016

Effect of IL6 and IL23 on double negative T cells and anti ds-DNA in systemic lupus erythematosus patients.

Hum Immunol 2016 Oct 23;77(10):937-943. Epub 2016 Jun 23.

Medical Microbiology & Immunology, Faculty of Medicine Assiut University, Assiut, Egypt.

Several evidences suggest that DN T cells, IL23 and IL6 play a role in the pathogenesis of SLE. This study aimed to evaluate the frequency of DN T cells in SLE patients and the relation to their activity also to assess the possible role of IL6 and IL23 on DN T cells. Thirty patients with SLE and sixteen healthy blood donor females were enrolled. There was a significant increase in DN T cells in patients than controls (P=0.001). These cells had a significant positive correlation with SLEDAI (r=0.486, P=0.006). DN T cells from SLE patient samples were expanded when stimulated in vitro with RhIL6 or RhIL23 in patients than controls. Furthermore, anti ds-DNA level was found to be increased in supernatant of PBMCs when stimulated by these cytokines in different concentrations. Our findings suggest that IL6 and IL23 may play role in SLE pathogenesis through their effect on DN T cells and anti ds-DNA.
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http://dx.doi.org/10.1016/j.humimm.2016.06.007DOI Listing
October 2016

The efficacy of hepatitis B vaccination program in upper Egypt: Flow cytometry and the evaluation of long term immunogenicity.

J Med Virol 2016 09 11;88(9):1567-75. Epub 2016 Mar 11.

Department of Pediatric Nursing, Faculty of Nursing, Sohag University, Egypt.

Anti-HBs levels wanes with time. Many studies discussed the B cell response to HBV vaccine. However, the data about memory T cell response are limited. To evaluate the efficacy of hepatitis B vaccine via evaluating anti-HBs levels and HBsAg specific memory T-lymphocytes through descriptive study. The study was conducted in a tertiary care setting. This study included 440 vaccinated persons during infancy. Group I: 6 to less than 10 years old; Group II: 10 to less than 14 years old; Group III: 14 to less than 17 years old; Group IV: 17 years old. The serum samples were screened for HBV markers. Cytokines secretion by HBsAg-specific memory CD45RO(+) CD4(+) T cells was measured after in vitro culture using flow cytometry. The mean titer of anti-HBs was higher in group I in comparison to others (P-value = 0.000 for each). IFN-γ and IL-4 secreted by memory CD4(+) T cells were positive in all with anti-HBs >100 mIU/ml, while positive in 87% and 75% of participants with anti-HBs <10 mIU/ml and positive in 73% and 32% of participants with absent anti-HBs. The percentage of cells secreting IFN-γ and those secreting IL-4 were higher among participants with serum anti-HBs >100 mIU/ml than those having <10 mIU/ml or absent (P < 0.001 for each). Anti-HBs positivity decreased with time since childhood vaccination. Breakthrough infections are rare in vaccinated persons. Hepatitis-B vaccine is efficient in controlling HBV infection. Flow cytometry is a useful tool to assess the long term persistence of T cell memory after childhood vaccination. J. Med. Virol. 88:1567-1575, 2016. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/jmv.24506DOI Listing
September 2016

Strong association between long and heterogeneous telomere length in blood lymphocytes and bladder cancer risk in Egyptian.

Carcinogenesis 2015 Nov 5;36(11):1284-90. Epub 2015 Sep 5.

Department of Biostatistics, Bioinformatics, and Biomathematics, Cancer Prevention and Control Program,

Although it is widely recognized that telomere dysfunction plays an important role in cancer, the relationship between telomere function and bladder cancer risk is not well defined. In a case-control study of bladder cancer in Egypt, we examined relationships between two telomere features and bladder cancer risk. Telomere fluorescent in situ hybridization was used to measure telomere features using short-term cultured blood lymphocytes. Logistic regression was used to estimate the strength of association between telomere features and the risk of urothelial carcinoma of the bladder. High telomere length variation (TLV) across all chromosomal ends was significantly associated with an increased risk of bladder cancer [adjusted odds ratios (OR) = 2.22, 95% confidence interval (CI) = 1.48-3.35], as was long average telomere length (OR = 3.19, 95% CI = 2.07, 4.91). Further, TLV and average telomere length jointly affected bladder cancer risk: when comparing individuals with long telomere length and high TLV to those with short telomere length and low TLV, the adjusted OR was 14.68 (95% CI: 6.74-31.98). These associations were stronger among individuals who are 60 years of age or younger. In summary, long and heterogeneous telomere length in blood lymphocytes was strongly associated with an increased bladder cancer risk in Egyptian and the association was modulated by age.
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http://dx.doi.org/10.1093/carcin/bgv121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4635668PMC
November 2015

Molecular chaperone GRP78 enhances aggresome delivery to autophagosomes to promote drug resistance in multiple myeloma.

Oncotarget 2015 Feb;6(5):3098-110

The Vontz Center for Molecular Studies, University of Cincinnati College of Medicine, Cincinnati, OH, USA.

Despite the clinical benefit of the proteasome inhibitor bortezomib, multiple myeloma (MM) patients invariably relapse through poorly defined mechanisms. Myeloma cells inevitably develop chemoresistance that leads to disease relapse and patient-related deaths. Studies in tumor cell lines and biopsies obtained from patients refractory to therapy have revealed that myeloma cells adapt to stress by inducing expression of glucose-regulated protein 78 (GRP78), an endoplasmic reticulum (ER) chaperone with anti-apoptotic properties. Treatment of myeloma cells with bortezomib increased GRP78 levels and activated GRP78-dependent autophagy. Expression profiling indicated that GRP78-encoding HSPA5 was significantly upregulated in bortezomib-resistant cells. Co-treatment with the anti-diabetic agent metformin suppressed GRP78 and enhanced the anti-proliferative effect of bortezomib. Bortezomib treatment led to GRP78 co-localization with proteotoxic protein aggregates, known as aggresomes. Pharmacologic suppression, genetic ablation or mutational inactivation of GRP78 followed by bortezomib treatment led to the accumulation of aggresomes but impaired autophagy and enhanced anti-myeloma effect of bortezomib. GRP78 was co-immunoprecipitated with the KDEL receptor, an ER quality control regulator that binds proteins bearing the KDEL motif to mediate their retrieval from the Golgi complex back to the ER. Taken together, we demonstrate that inhibition of GRP78 functional activity disrupts autophagy and enhances the anti-myeloma effect of bortezomib.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4413640PMC
http://dx.doi.org/10.18632/oncotarget.3075DOI Listing
February 2015

Increased susceptibility to apoptosis and growth arrest of human breast cancer cells treated by a snake venom-loaded silica nanoparticles.

Cell Physiol Biochem 2014 3;34(5):1640-51. Epub 2014 Nov 3.

Laboratory of Immunology & Molecular Biology, Zoology Department, Faculty of Science, Assiut University, Assiut, Egypt.

Background: The development of effective treatments against metastatic cancers, including breast cancer, is among the most important challenges in current experimental and clinical cancer research. We recently demonstrated that Walterinnesia aegyptia venom (WEV), either alone or in combination with silica nanoparticles (WEV+NP), resulted in the growth arrest and apoptosis of different cancer cell lines.

Aims: In the present study, we evaluated the impact of WEV alone and WEV+NP on human breast cancer cells isolated from cancer biopsies.

Methods: The potential effects of WEV alone and WEV+NP on the proliferation, induction of apoptosis and generation of free radicals in breast cancer cells isolated from 80 patients clinically diagnosed with breast cancer were evaluated by flow cytometry and ELISA.

Results: WEV alone and WEV+NP inhibited the proliferation, altered the cell cycle and enhanced the induction of apoptosis of the breast cancer cells by increasing the activities of caspase-3, caspase-8 and caspase-9. In addition, the combination of WEV and NP robustly sensitized the breast cancer cells to growth arrest and apoptosis by increasing the generation of free radicals, including reactive oxygen species (ROS), hydroperoxide and nitric oxide. The combination of WEV with NP significantly enhanced the anti-tumor effect of WEV in breast cancer cells.

Conclusion: Our data indicate the therapeutic potential of the nanoparticle-sustained delivery of snake venom for the treatment of breast cancer.
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http://dx.doi.org/10.1159/000366366DOI Listing
August 2015

Circulating Endothelial Cells and Platelet Microparticles in Mitral Valve Disease With and Without Atrial Fibrillation.

Angiology 2015 Aug 12;66(7):631-7. Epub 2014 Aug 12.

Department of Cardiology, Faculty of Medicine, Assiut University, Assiut, Egypt.

Hypercoagulability in mitral valve disease (MVD), a cause of atrial fibrillation (AF) and stroke, is potentially due to endothelial damage/dysfunction (marked by circulating endothelial cells [CECs]), platelet activation (soluble P-selectin [sPsel], platelet microparticles [PMPs], and soluble CD40 [sCD40]), and oxidized low-density lipoprotein (oxLDL) cholesterol. We measured these variables in 24 patients with MVD as well as in 21 with MVD + AF and compared them with 20 healthy controls (HCs). The CECs and PMPs were measured by flow cytometry; sPsel, oxLDL, and CD40 by enzyme-linked immunosorbent assay. Compared with HCs, sPsel and PMPs were equally higher in MVD and MVD + AF; sCD40 and oxLDL were higher in MVD + AF than in HCs and MVD; and CECs were higher in MVD than in the HCs, with further increases in MVD + AF (all P < .001). We conclude that excess platelet activation is present in MVD regardless of AF, and that increased endothelial damage in MVD is greater when compounded by AF.
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http://dx.doi.org/10.1177/0003319714546183DOI Listing
August 2015

Effect of thoracic epidural analgesia on pro-inflammatory cytokines in patients subjected to protective lung ventilation during Ivor Lewis esophagectomy.

Pain Physician 2014 Jul-Aug;17(4):305-15

South Egypt Cancer Institute, Assuit University, Egypt.

Background: Thoracic epidural analgesia (TEA) has a well-known effect on neurohormonal response. Attenuation of stress response by post-operative epidural analgesia has shown beneficial effects such as lower pain scores and less immunological alterations.

Objectives: Investigation of the combined effects of TEA and protective lung ventilation on pro-inflammatory cytokines and patients' outcome after Ivor Lewis esophagectomy.

Study Design: A randomized controlled study.

Setting: Academic medical center.

Methods: Thirty patients of the American Society of Anesthesiologists (ASA) I and II were randomly allocated into 2 groups: G1 (n = 15) patients received general anesthesia and were mechanically ventilated with 9 mL/kg during 2 lung ventilations, reduced to 5 mL/kg and 5cm H2O positive end expiratory pressure (PEEP) during one lung ventilation (OLV) or GII) (n = 15) patients received TEA and the same general anesthesia and mechanical ventilation used in G1. Assessment parameters included hemodynamics, pain severity, total analgesic consumption, and measurement of interleukins (IL) (IL-6 and IL-8) at baseline time after anesthetic induction (TBaseline,); at the end of the abdominal stage of the operation (TAbdo,); 15 minutes after initiation and at the end of OLV (TOLV 15) and (TOLV End) respectively; one and 20 hours after the end of the surgical procedure (TPostop1 and TPostop20), respectively, and patient's outcome also recorded.

Results: There was a significant reduction in mean arterial blood pressure (MAP) and pulse rate in GII during the intraoperative period, at Tabdo, TOLV15, and TOLV End (P < 0.05). The mean of systolic blood pressure (SBP) values were significantly lower in GII over all 3 post-operative days (P = 0.001), and the mean diastolic blood pressure (DBP) showed a significant reduction in GII for 16 hours post-operatively (P = 0.001). The mean of heart rate values showed a significant reduction in GII over all 3 post-operative days in comparison to GI (P = 0.001). The mean resting and dynamic VAS scores were significantly reduced in GII at all time periods studied in comparison to G1 (P = 0.001). The daily PCA morphine consumption was markedly decreased in GII compared to GI in the first 3 days post-operatively (P = 0.001). There were significant reductions in blood level of IL-6 and IL-8 in GII compared to G1 over the entire study period (P < 0.05). There were no significant differences in post-operative adverse effects between the 2 groups (P > 0.05). The duration of stay in PACU was significantly decreased in GII (10 ± 2 days) compared to GI (15 ± 3 days) (P = 0.001).

Limitations: This study is limited by its sample size.

Conclusion: Our study concluded that TEA reduced the systemic pro-inflammatory response and provided optimal post-operative pain relief. Although there were no significant differences in adverse events, there was a trend towards improved outcome. Further clinical studies with larger numbers of patients are required.
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November 2014

Regulatory T cell subsets in children with systemic lupus erythematosus.

Clin Rheumatol 2014 Aug 27;33(8):1085-91. Epub 2014 May 27.

Department of Pediatric, Faculty of Medicine, Assiut University, Assiut, Egypt,

The aim of this work was to quantify CD4(+)CD25(+)Foxp3(+) T cells (Tregs) in Egyptian children with SLE and to correlate these findings with their disease activity scores and drug therapy. We enrolled 37 Egyptian children with active SLE. Disease activity was assessed by measuring serum levels of anti-dsDNA antibody and by the SLEDAI scores. Twenty healthy children were also enrolled as normal controls. The CD4+CD25+, CD4+CD25(bright), and CD4+CD25(dim) cells in patients were significantly increased in comparison to controls. There was no significant difference in the Foxp3 gated on CD4+CD25(bright) and CD4+CD25(dim), but there was a significant increase when gated on CD4+CD25- and whole CD4+ cells in patients than controls. There was no significant difference among patients with different degrees of activity on different lines of treatments and their outcomes as regards all studied values. There was no significant correlation between SLEDAI score and any of the studied parameters except for a significant negative correlation with gated lymphocytes. There is increased expression of Foxp3 in CD4+ T cells mostly CD25- in Egyptian children with active SLE under corticosteroid treatment regardless of disease activity.
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http://dx.doi.org/10.1007/s10067-014-2636-9DOI Listing
August 2014

Subclinical vascular endothelial dysfunctions and myocardial changes with type 1 diabetes mellitus in children and adolescents.

Pediatr Cardiol 2014 Aug 5;35(6):965-74. Epub 2014 Mar 5.

Pediatric Department, PICU, Children University Hospital, Assiut University, B.O, 71111, Assiut, Egypt,

Vascular endothelial dysfunction, accelerated thickening of arterial intima, and changes in ventricular functions contribute to increased cardiovascular morbidity in type 1 diabetes mellitus (T1DM). This study aimed to investigate the functional-structural changes in the arteries and myocardium together with affection of highly sensitive C-reactive protein (hsCRP), circulating endothelial cells (CECs), and vitamin C levels in children with T1DM. Also, to test the association with early atherosclerotic changes. The study included 30 children with a diagnosis of T1DM and 30 healthy subjects matched by sex, age, and body mass index. Serum lipids, HbA1c, hsCRP, vitamin C, and CECs were detected. Corrected QT interval (QTc), cardiac dimensions, and left ventricular (LV) functions were assessed using conventional echocardiography. Noninvasive ultrasound was used to measure brachial artery flow-mediated dilation (FMD) responses and carotid intima-media thickness (IMT). The QTc interval was significantly higher in the diabetic patients than in the control subjects (P < 0.001). The findings showed LV diastolic dysfunction as reflected by significantly lower early peak flow velocity, decreased E/A ratio, increased early filling deceleration time (DcT), and prolonged isovolumic relaxation time (IVRT) (P < 0.001 for each). The children with diabetes had a significantly lower FMD response, increased IMT, lower vitamin C level, higher hsCRP, and higher CEC compared with the control subjects (P < 0.001 for each). A positive correlation between CEC and HbA1c was found (P = 0.004). An alteration in myocardial function and endothelial dysfunction may begin early with the association of early atherosclerotic changes. These changes are accelerated when glycemic control is poor. The authors recommend early and close observation of children with diabetes for any alterations in cardiac and vascular endothelial function. Vitamin C supplementation may reduce the risk of complications.
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http://dx.doi.org/10.1007/s00246-014-0883-9DOI Listing
August 2014

Diabetes worsening of hepatitis C cirrhosis: are alterations in monocytic tissue factor (CD 142) is the cause?

Ann Hepatol 2013 Jan-2014 Feb;13(1):27-37

Department of Internal Medicine, Minia University, Minia, Egypt.

BACKGROUND & AIM. The mechanisms by which type 2 diabetes mellitus (T2DM) worsen liver function are not yet established. Tissue factor (TF) is a protein that participates in hemostatic, immune and inflammatory processes. To test the hypothesis that T2DM contributes to clinical outcome through changes of TF expression on monocytes and to investigate the association between antidiabetic therapies and monocytic TF expression in HCV-related cirrhotic patients with T2DM. MATERIAL AND METHODS. In HCV-related cirrhotic patients (139 diabetics and 130 non diabetics) compared with 100 matched diabetic patients and 100 Controls; the flowcytometric analysis of CD14, TF (CD142), costimulatory molecules; CD86 and HLA-DR on monocytes were determined. RESULTS. Cirrhotic patients with T2DM have increase in the expression of monocytic TF and CD86 in comparison with cirrhotic non-diabetic, diabetic and healthy control; which increase significantly with increase of the stage of the Child-Pugh score. The expression of HLA-DR is significantly lower in cirrhotic patients than controls. Albeit, there were no significant differences in the HbA1c levels between the three groups, the use of exogenous insulin were associated with significantly higher monocytic TF expression than those in sulphonylurea and insulin sensitizer group (P < 0.03 for both). CONCLUSIONS. The monocytic TF as a significant link connecting inflammatory and immunological phenomena can partially explain a lot of events in HCV- related cirrhotic patients with T2DM. The use of exogenous insulin was associated with significantly higher TF expression than sulphonylurea and insulin sensitizer. Future target therapy against TF may be beneficial for T2DM cirrhotic patients.
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September 2014

p-Stat3 and bcr/abl gene expression in chronic myeloid leukemia and their relation to imatinib therapy.

Leuk Res 2014 Feb 24;38(2):243-50. Epub 2013 Nov 24.

Department of Clinical Pathology, South Egypt Cancer Institute, Assiut University, Egypt.

Flowcytometry analysis was carried out to evaluate the expression of the p-Stat3 in 50 CML patients and 20 age-matched healthy controls. p-Stat3 expression was increased in advanced stages of CML. Imatinib treatment was found to suppress the expression of p-Stat3 in bone marrow cells. The level of p-Stat3 was found to be higher in resistant cases than in responsive cases, which suggest the beneficial use of p-Stat3 as an indicator to follow the clinical course and the treatment response.
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http://dx.doi.org/10.1016/j.leukres.2013.11.012DOI Listing
February 2014

Is Foxp3 a good marker for regulatory T cells?

Egypt J Immunol 2014 ;21(2):1-8

To track the changes in the tested Treg markers especially Foxp3 following activation to determine whether data of human studies using Foxp3 in evaluation of Tregs are reliable or not. Four-colour flow cytometry analysis was carried out to calculate the percentages of Tregs before and after lymphocyte activation. Foxp3 expression by CD4(+)CD25(+)* and CD4(+)CD25(high) T cells increased after T cell activation. A moderate negative correlation was observed between the percentage of each of CD4(+)CD25(+)Foxp3(+)IL10(+) or CD4(+)CD25(high) Foxp3(+)IL10(+) T cells and the percentage of CD4(+)CD25(+) T cells "after activation" and a weak negative correlation was similarly observed between the percentage of CD4(+)CD25(-)Foxp3(+)IL10(+) T cells and the percentage of CD4(+)CD25(+) T cells "after activation". A moderate negative correlation was observed between the percentage of each of CD4(+)CD25(+)Foxp3(+)IL10(+), CD4(+)CD25(high)Foxp3(+)IL10(+) or CD4(+)CD25(-) Foxp3(+)lL10(+) T cells and the percentage of CD4(+)CD25(high) T cells "after activation". CD4(+)CD25(high) T cell subpopulation expressed a significantly higher level of intracellular Foxp3 compared with CD4(+)CD25(low) and CD4(+)CD25(-) T cells subpopulations. In conclusions, Foxp3 is a good marker of Tregs especially if panels of markers were used for their identification. CD4(+)CD25(high) Foxp3(+) T cell subpopulation mostly represents Tregs and thus should be the one targeted in Treg studies.
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April 2015