Publications by authors named "Roba M Talaat"

44 Publications

Therapeutic Potential of Targeted-Gold Nano-spheres (AuNSs) on collagen-induced arthritis (CIA) in rats.

Clin Exp Pharmacol Physiol 2021 Jun 1. Epub 2021 Jun 1.

Molecular Biology Department, Genetic Engineering and Biotechnology Research Institute (GEBRI), University of Sadat City (USC), Egypt.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that causes functional disability due to bone destruction and severe joint pain. Current anti-rheumatic treatments develop severe complications and do not provide complete remission. Gold nanoparticles (AuNPs) have garnered attention because of their unique physical and chemical properties. In this study, we have evaluated the therapeutic effects of gold nanospheres (AuNSs) with two different ligands (targeted- nanoparticles) against collagen-induced arthritis (CIA) and compared the outcomes with conventional Methotrexate (MTX) and biological (Infliximab) treatments. Clinical evaluation was performed by radiographic and histological examinations. Besides, the bioaccumulation of AuNSs in vital organs was assessed. The mechanistic studies targeting pro-inflammatory/anti-inflammatory and angiogenic mediators' expressions were performed. Radiographic examination showed that the targeted AuNSs reduced joint space narrowing and bone erosion. Moreover, histopathological examination of rat ankle joints demonstrated that targeted AuNSs reduce bone and cartilage degeneration/inflammation. Gold nanospheres-conjugated with nucleus localized peptide (nuclear membrane-targeted) ([email protected]) has resolved bone destruction and inflammation compared to gold nanospheres-conjugated at polyethylene glycol ([email protected]). Although the AuNSs accumulated in different organs in both cases, they didn't induce any toxicity or tissue damage. The two different targeted AuNSs significantly suppress inflammatory and angiogenic mediators' expression and induced anti-inflammatory cytokine production, but the [email protected] superior therapeutic efficacy. In conclusion, these results suggested that nuclear membrane-targeted AuNSs effectively attenuated arthritis progression without systemic side effects.
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http://dx.doi.org/10.1111/1440-1681.13531DOI Listing
June 2021

The Impact of Interferon-γ (IFN-γ) and IFN-γ-Inducible Protein 10 (IP-10) Genes' Polymorphism on Risk of Hepatitis C Virus-Related Liver Cirrhosis.

Immunol Invest 2021 Jan 14:1-17. Epub 2021 Jan 14.

Molecular Biology Department, Genetic Engineering and Biotechnology Research Institute (GEBRI), University of Sadat City (USC), Sadat City, Egypt.

: Today there is increasing evidence concerning the association between individual genetic polymorphisms within proinflammatory cytokines and chronic hepatitis C (CHC) severity. It has been demonstrated that polymorphisms in some genes may significantly predict HCV infected patients' susceptibility to developing liver cirrhosis or their responsiveness to the treatment.: We investigated the influence of single nucleotide polymorphisms (SNPs) in Interferon (IFN-γ) and Interferon Gamma-Inducible Protein 10 (IP-10) genes on cirrhosis risk in HCV-infected patients and their association with response to various direct-acting antiviral drugs (DAAs).: IFN-γ (+874T/A, +2109A/G) and IP-10 (-135G/A, -1447A/G) genotypes were determined in 175 CHC Egyptian HCV patients (69 liver cirrhotic and 106 non-cirrhotic patients) using either single-stranded polymorphism polymerase chain reaction (SSP-PCR) or Restriction fragment length-PCR (RFLP-PCR) methods.: IFN-γ + 874 TA, IP-10 - 135AA, and IP-10 - 1447AA and IP-10 - 1447GG genotypes are increased in patients developing liver cirrhosis compared to non-cirrhotic ones. Although, no statistical significance in their distribution was demonstrated, indicating the lack of association between these SNPs and liver cirrhosis susceptibility in HCV-infected patients. Haplotypes analysis between different loci on all selected genes showed a significant increase in AGGA and TAGA and a significant decrease in TGGA haplotypes in cirrhotic patients. Genotype frequencies at loci -135 and -1447 of IP-10 appeared to be in complete Linkage disequilibrium (LD) (D' = 0.999, r = 0.689).: Our data support the concept that IFN-γ and IP-10 gene polymorphisms are not predictors of disease progression among Egyptian patients with HCV infection.
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http://dx.doi.org/10.1080/08820139.2020.1869251DOI Listing
January 2021

Regulation of CD4CD25FOXP3 cells in Pediatric Acute Lymphoblastic Leukemia (ALL): Implication of cytokines and miRNAs.

Mol Immunol 2020 08 30;124:1-8. Epub 2020 May 30.

Molecular Biology Department, Genetic Engineering and Biotechnology Research Institute (GEBRI), University of Sadat City, Sadat, Egypt. Electronic address:

Regulatory T cells (Tregs) is one of the immunosuppressive subsets of CD4 T cells characterized by transcription factor forkhead box protein P3 (FOXP3) expression which are involved in tumor development and progression. Identification of the factors that influence Treg cell function is extremely important. Our current study aimed to evaluate the frequency of Treg cells, cytokine secretion and the expression of microRNAs (miRNAs) in pediatric acute lymphoblastic leukemia (ALL) patients. The frequency of CD3, CD4 and CD4CD25FOXP3 Treg was assessed by flow cytometry in 43 ALL patients versus 42 controls. Plasma levels of IL-10, transcription factor β (TGF-β), IL-6, IL-17, IL-23 and tumor necrosis factor (TNF-α) were measured by Enzyme-linked immunosorbent assay (ELISA). miR-21, miR-24, miR-26a, miR133b, miR-148a and miR-155 expression were analyzed using quantitative real-time polymerase chain reaction (qRT-PCR). A slight insignificant increase in Treg cells in ALL patients compared to controls was observed. There was a significant elevation in IL-10 (p < 0.05), IL-6 (p < 0.01), IL-23 (p < 0.05) and TNF-α (p < 0.01) in ALL patients compared with controls. Meanwhile, a significant reduction in TGF-β (p < 0.001) was recorded. A slight insignificant decrease in IL-17 in ALL patients was observed.ALL patients showed a significant increase in miR-21 (p < 0.05), miR-148a (p < 0.01), miR-24 (p < 0.05) and a significant reduction in miR-155 (p < 0.01). In conclusion, the slight change in Treg cells frequency and alteration in related cytokines could possibly involve in the pathogenesis of ALL. Dysregulated miRNAs, as a regulatory mechanism of epigenetics, might contribute to these observed results. Further researches are required to confirm our interesting findings.
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http://dx.doi.org/10.1016/j.molimm.2020.05.002DOI Listing
August 2020

Cytokine and inflammatory mediators are associated with cytotoxic, anti-inflammatory and apoptotic activity of honeybee venom.

J Complement Integr Med 2020 May 26;18(1):75-86. Epub 2020 May 26.

Molecular Biology Department, Genetic Engineering and Biotechnology Research Institute (GEBRI), University of Sadat City (USC), Sadat, Egypt.

Objective: The present study aimed to evaluate cytotoxic, apoptotic, and anti-inflammatory properties of bee venom (BV) as well as changes in cytokine secretion levels and nitric oxide (NO) production using three different cancer cell lines [liver (Hep-G2), breast (MCF-7), and cervical (HPV-18 infected HeLa cells)] and two normal cells (splenocytes and macrophages (MQ).

Methods: Cytotoxic activity of BV against tumor cell lines and normal splenocytes/MQ was tested by MTT assay. By ELISA (ELISA); Tumor necrosis factor (TNF-α), Interleukine (IL-10) and interferon (IFN-γ) were measured. Caspase three expressions was evaluated using reverse transcription-polymerase chain reaction (RT-PCR). Nitric oxide (NO) was estimated using a colorimetric assay.

Results: BV has a significant cytotoxic effect on all cell lines in a dose- and time-dependent manner; none of them was toxic for normal cells. Treating Hep-G2 cells with BV showed a reduction in IL-10, elevation in TNF-α with no change in IFN-γ level. MCF-7 cells have low IL-10 and TNF-α and high IFN-γ production level. Elevation of IL-10 and IFN-γ coincides with a reduction in TNF-α level was demonstrated in HeLa cells. The expression of Caspase three was dramatically increased with elevation in BV concentration in all tested cancer cell lines. A gradual decrease in NO production by MQ with increasing BV dose was observed.

Conclusion: Taken together, our results stressed on the importance of BV as a potent anti-tumor agent against various types of cancers (Liver, Breast, and Cervix). Further steps towards the use of BV for pharmacological purposes must be done.
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http://dx.doi.org/10.1515/jcim-2019-0182DOI Listing
May 2020

Crosstalk between miR-215 and epithelial-mesenchymal transition specific markers (E-cadherin and N-cadherin) in different stages of chronic HCV Infection.

J Med Virol 2020 08 30;92(8):1231-1238. Epub 2019 Dec 30.

Department of Molecular Biology, Genetic Engineering and Biotechnology Research Institute, University of Sadat City, Sadat City, Egypt.

The main causes of death among patients with hepatocellular carcinoma (HCC) are a recurrence, metastasis, and deterioration of primary tumors by the epithelial-to-mesenchymal transition (EMT) which is controlled by several molecules including E-cadherin and N-cadherin. Microribonucleic acids (miRNAs) have been identified to play a regulatory role in EMT. miR-215 is important in repressing migration/invasion of cancer cells. In this study, we aimed to evaluate the crosstalk between miR-215 and EMT specific markers (E-cadherin and N-cadherin) with a spotlight on its role in the EMT process in hepatitis C virus (HCV)-infected patients. One hundred forty-five patients were studied, 75 had HCV-induced cirrhosis classified into child A, B, and C and 25 had HCC. In parallel, 45 healthy volunteers considered as controls. Serum levels of E- and N-cadherin were measured using enzyme-linked immunosorbent assay and miR-215 expression measured by a quantitative reverse transcription-polymerase chain reaction. Insignificant change in serum levels of E-cadherin and N-cadherin in HCV-infected patients compared with normal controls was observed with a slight increase in E-cadherin and N-cadherin in the child B group. HCC patients had the lowest amount of E-cadherin and N-cadherin compared with cirrhotic and normal subjects. A maximum reduction in miR-215 was observed in HCC patients compared with cirrhotic and control ones. A positive correlation (r = .202; P < .05) was observed between miR-215 and E-cadherin. Our data stressed on the potential role of miR-215 as an important mediator in HCC progression. miRNAs participating in EMT needs further studies to provide insight into the metastasis of HCC.
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http://dx.doi.org/10.1002/jmv.25637DOI Listing
August 2020

Combined Hyperthermia and Radiation Therapy for Treatment of Hepatocellular Carcinoma.

Asian Pac J Cancer Prev 2019 08 1;20(8):2303-2310. Epub 2019 Aug 1.

Egyptian Atomic Energy Authority, Department of Radioisotope, Cairo, Egypt.

Background: There is no doubt that hyperthermia is one of the powerful radiosensitizers. Finding a proper mechanism working in hyperthermia/radiation combination is still pronounced challenge. Objectives: This study is focusing on the anti-cancer activities (anti-proliferative, anti-angiogenic and antiapoptotic) of thermoradiotherapy. Materials and Methods: Liver cancer cell line (HepG2) was treated by 37oC, 40oC and 43oC hyperthermia degrees combined with three radiation doses (2 Gy, 4 Gy and 8 Gy) for 24, 48 and 72 hrs. Cell viability, apoptotic/necrotic cell screening, apoptotic (BAX and FasL) and antiapoptotic (BCL-2 and GRP78) genes, and pro-angiogenic mediators [vascular endothelial- (VEGF) and Platelet derived-growth factors (PDGF) ware investigated. Results: Our data showed that 40oC temperature combined with 4 Gy radiation gives a significant decrease (p<0.05) in cell viability. Maximum cytotoxicity was reported 48 hr post-treatment followed by slight restoration of cell viability after 72 hr. Compared with untreated cells, only 5% of viable cells with a high percentage of apoptotic (31%) and necrotic (63%) cells were demonstrated in 40oC/4 Gy/48 hr group. Expression of pro-apoptotic genes (BAX and FasL) were increased after hyperthermia with apparent elevation in 40oC/4 Gy/48 hr group coincides with moderate expression of antiapoptotic BCL-2 and GRP78 genes. A significant reduction (p<0.001; p<0.05) in VEGF and PDGF levels; respectively was shown at 40oC/4 Gy/48 hr group. Conclusions: This pilot study proposed 40oC mild temperature hyperthermia as a favorable hyperthermal condition with 4 Gy radiotherapy in HCC treatment. A further research has to be performed considering an application of more than one session of radiothermal therapy at 40oC/4 Gy for total abrogation of cancer cells.
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http://dx.doi.org/10.31557/APJCP.2019.20.8.2303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6852830PMC
August 2019

Genetic variation in microRNA-100 (miR-100) rs1834306 T/C associated with Hepatitis B virus (HBV) infection: Correlation with expression level.

Infect Genet Evol 2019 09 6;73:444-449. Epub 2019 Jun 6.

Biochemistry Department, Faculty of Pharmacy, Cairo University, Egypt. Electronic address:

Circulating microRNAs (miRNAs) have a vital role in Hepatitis B virus (HBV) diagnosis and therapeutics. miR-100 was reported to be associated with various aspects of HBV biology. This study focused on a miR-100 Single Nucleotide Polymorphism (SNP) (rs1834306 T/C) and its contribution to an individual's susceptibility and prognosis of HBV infection. The effect of SNP on miR-100 expression will be also evaluated. Two hundred subjects: 100 HBV infected patients and 100 age-and-sex-matched healthy individuals served as a control group. SNP detection was performed using polymerase chain reaction technique with sequence-specific primers (PCR-SSP) method and miR-100 expression through quantitative real-time PCR (qRT-PCR). Our result showed a significant up-regulation of miR-100 expression in HBV patients versus the control group (P < .01). A positive correlation was found between viral load and elevation in miR-100 expression (r = 0.508; P < .01). Concerning miR-100 expression in different genotypes/alleles, TC genotype and T allele in coincides with a significantly elevated expression level of miR-100 (P < .001) in HBV patients than in controls. Best of our knowledge, it is the first observational prospective case-control study concerned with miR-100 (rs1834306 T/C) SNP in the Egyptian population. However, the small size of this preliminary work required more prospective investigations to confirm our data.
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http://dx.doi.org/10.1016/j.meegid.2019.06.009DOI Listing
September 2019

IL-17, IL-10, IL-6, and IFN-γ in Egyptian Behçet's disease: correlation with clinical manifestations.

Eur Cytokine Netw 2019 Mar;30(1):15-22

National Research Centre (NRC) , Medical physiology Department, Egypt.

There are a limited number of studies that report the polarization of the immune system toward the production of T helper 1 (Th1), Th2, or Th17-type cytokines in patients with Behçet's disease (BD). Here, we aimed to detect the presence of various cytokines in serum samples of Egyptian BD patients and to determine the correlation between their production levels and clinical manifestations. To that aim, serum levels of IFN-γ, IL-10, IL-6, and IL-17 measured by ELISA were determined in BD patients with active or inactive disease to evaluate their clinical relevance. The results of the present study show significantly elevated levels of IL-17 and IL-6, as well as a reduction in IL-10, and no change in IFN-γ, in sera of BD patients, as compared to the healthy control group. Moreover, IL-6 serum levels were increased in BD patients in active stages of disease and correlated with arthritic manifestations. On the other hand, IL-10 serum levels were significantly decreased in patients with gastrointestinal tract complications. Furthermore, a positive correlation was observed between IL-10 serum levels and ocular manifestations in BD patients, in contrast to those of IL-17, showing no correlation with the different clinical manifestations. Taken together, the magnitude of IL-6 serum levels could be a potential marker for arthritic manifestations and disease activity, whereas those of IFN-γ, IL-10, and IL-17 cannot be considered predictors for different clinical manifestations in patients with BD.
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http://dx.doi.org/10.1684/ecn.2019.0421DOI Listing
March 2019

Clinical Impact of Circulated miR-1291 in Plasma of Patients with Liver Cirrhosis (LC) and Hepatocellular Carcinoma (HCC): Implication on Glypican-3 Expression.

J Gastrointest Cancer 2020 Mar;51(1):234-241

Molecular Biology Department, Genetic Engineering and Biotechnology Research Institute (GEBRI), Sadat City University, Sadat City, Egypt.

Purpose: Liver cirrhosis (LC) is considered to be the end stage of chronic hepatopathies which may lead to hepatocellular carcinoma (HCC). Glypican-3 is one of the most promising serum markers for HCC. Abnormal expression of miRNAs may participate in cancer development and progression. In this study, we aimed to evaluate the relation between the expression of miR-1291 and GPC3 production as a non-invasive tool to differentiate patients with LC and HCC.

Methods: HCV patients (100) were divided into two groups; HCC (I) and LC (II). Fifty hepatitis-free subjects served as the control group (III). Expression of serum GPC3 was performed by enzyme-linked immunosorbent assay, and expression of circulating miR-1291 was performed by quantitative real-time polymerase chain reaction (qRT-PCR).

Results: Serum levels of GPC3 were significantly elevated in patients with HCC compared with the LC group. Both groups have increased GPC3 levels in relation to healthy controls. Serum GPC3 levels with a cutoff value of 619.5 pg/ml had a 50% sensitivity and 89.3% specificity while alpha-fetoprotein (AFP) with a cutoff value of 8.5 ng/ml had a higher sensitivity (87.5%) and specificity (100%) in the detection of HCC. The primary use of both markers improved the specificity to 100%. miR-1291 was significantly upregulated in HCC and LC patients compared with control subjects.

Conclusions: Our findings might indicate that miR-1291 exert oncogenic effects in hepatic carcinogenesis through positive regulation of GPC3 expression. We propose that GPC3 overexpression and its associated oncogenic effects are linked to the upregulation of miR-1291 in HCV patients.
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http://dx.doi.org/10.1007/s12029-019-00234-9DOI Listing
March 2020

Bifidobacterium longum Suppresses Murine Colorectal Cancer through the Modulation of oncomiRs and Tumor Suppressor miRNAs.

Nutr Cancer 2019 12;71(4):688-700. Epub 2019 Mar 12.

h h Botany Department, Faculty of Science , Menofiya University , Egypt.

The modulatory role of the Bifidobacterium longum (BL), isolated from women breast milk, on some oncogenic and tumor suppressor miRNAs as well as IL-1β and IL6 targeted-miRNAs was investigated using murine colorectal cancer (CRC) induced on the top of inflammatory ulcerative colitis model. The investigation of the oncomiRs miR-21a and miR-155, which regulate IL-6 and IL-1β expression, indicated that both was depressed by BL-administration in healthy and in CRC-mice. BL-administration induced the tumor suppressor miRNAs (miR-145 and miR-15a) expression in both of the healthy and in CRC-mice. The miR-146a expression, which regulates both of IL-1β and IL-6 expression, was decreased after the BL-administration in both of the healthy and in CRC-mice. In CRC-mice, NF-Kb concentration was elevated, however this NF-Kb induction was diminished after the treatment with BL. BL highly enhanced the IL-1β and IL-6 mRNA and protein concentrations in healthy mice. The administration of BL to CRC-mice resulted in a dramatic increase in IL-1β mRNA and IL-1β concentration, which in contrast was accompanied with a decrease in the IL-6 mRNA and IL-6 concentration. BL-administration resulted in a drop in the aberrant crypt foci number in CRC-mice and increased necrosis and fibrosis of the colon cells. The modulatory influence of B. longum on microRNAs may provide an important therapeutic impact in CRC through inhibition of the proliferation, invasion, apoptosis, and cell cycle of tumor cells.
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http://dx.doi.org/10.1080/01635581.2019.1577984DOI Listing
May 2020

Interleukin-6 promotor gene polymorphisms and susceptibility to chronic hepatitis B virus in Egyptians.

Hum Immunol 2019 Mar 27;80(3):208-214. Epub 2018 Dec 27.

Biochemistry Department, National Liver Institute (NLI), Menoufiya University, Shebeen El-Kom, Menoufiya, Egypt.

Aim: To investigate the association between IL-6 polymorphisms (-174G/C, -572G/C and -597G/A) and susceptibility to chronic hepatitis B virus (CHB) infection.

Method: Total 108 subjects with CHB infection and 102 healthy controls were enrolled in this study. IL-6 (-174G/C) was genotyped using Mutagenically separated Polymerase Chain Reaction (MS-PCR) while sequence specific primers-PCR (SSP-PCR) was used for studying -572G/C and -597G/A. IL-6 plasma level was measured using Enzyme-linked immunosorbent assay (ELISA).

Results: A significant increase (P < 0.01, P < 0.01, P < 0.001) in -174GG, -572GC and -597GA; respectively in the CHB group compared to control group, while -572GG genotype was significantly decreased (P < 0.01) in CHB patients. A significant increase (p < 0.01, p < 0.01) in -174 G and -597A alleles was observed in the CHB patient group; respectively. GGA haplotype is significantly increased (P < 0.05) while GCA haplotype is significantly decreased (P < 0.001) in the patient group. A moderate linkage disequilibrium (LD) (D' = 0.719, r = 0.474; P < 0.001) between IL-6 (-572G/C and -597G/A) was observed. A significant reduction (P < 0.01) in IL-6 plasma level in CHB patients compared to healthy controls (22.28 ± 1.93 versus 32.08 ± 2.41), which was negatively correlated (r = -0.216; P < 0.01) with HBV infection.

Conclusions: This study pointed to the potential role of IL-6 (-174G/C, -572 G/C and -597G/A) gene polymorphisms in the susceptibility to HBV infection. Our results allow for only preliminary conclusions due to relatively small sample size. There is a need for further larger scale studies to fully examine the possible relationship between these cytokine gene polymorphisms and the development of CHB.
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http://dx.doi.org/10.1016/j.humimm.2018.12.009DOI Listing
March 2019

Association of C3435T, C1236T and C4125A Polymorphisms of the MDR-1 Gene in Egyptian Children with Acute Lymphoblastic Leukaemia

Asian Pac J Cancer Prev 2018 Sep 26;19(9):2535-2543. Epub 2018 Sep 26.

Molecular Biology Department, Genetic Engineering and Biotechnology Research Institute (GEBRI), University of Sadat City, Egypt. Email:

Background: P-glycoprotein (P-gp), a membrane transporter encoded by the multidrug resistance-1 (MDR1) gene, influences pharmacokinetics and metabolism of anticancer drugs and contributes to multidrug resistance phenotype in acute lymphoblastic leukemia (ALL). Genetic variation ofMDR1 in ALL patients is increasingly recognized as a factor influencing response to treatment. Aim: To investigate the possible role of MDR-1 gene polymorphisms (C3435T, C1236T and C4125A) as risk factors for the development and clinical outcome of ALL in Egyptian children. Materials and Methods: Genotyping of MDR-1 C3435T, C1236T and C4125A single nucleotide polymorphisms (SNPs) was accomplished using a polymerase chain reaction–restriction fragment length polymorphism (RFLP-PCR) assay with 120 childhood ALL patients and 100 healthy controls. Results: Homozygous T with the C3435T SNP showed a protective effect as compared to homozygous C (OR=0.748) while heterozygous CT correlated with a poor outcome (high risk, drug unresponsiveness, relapse and high percentage of death). Additionally, the T allele of the C1236T SNP showed a significant relation with ALL risk (OR=1.6). However, there were no significant differences in the genotype and allele frequencies of MDR-1 SNPs between patients and controls. Only one genotype (CC) and one allele of MDR-1 (C4125A) were seen. Neither CA/AA genotypes nor A alleles were present in ALL patients and normal controls. TC was the predominant haplotype in both groups, while CT proved to be minor. The cumulative incidence of relapse was higher with the CC genotype of C1236T as compared with TT. Conclusion: From our preliminary data, the CT genotype of C3435T is associated with a poor ALL outcome while the CC genotype of C1236T is related with an increased incidence of relapse. Although our results provide assistance for oncologist choice of individual therapeutic strategy taking the patient genetic repertoire into consideration, further investigations with larger sample size should be conducted to validate our results.
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http://dx.doi.org/10.22034/APJCP.2018.19.9.2535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6249480PMC
September 2018

Upregulation of miR-221/222 expression in rheumatoid arthritis (RA) patients: correlation with disease activity.

Clin Exp Med 2019 Feb 21;19(1):47-53. Epub 2018 Aug 21.

Sadat City University, Sadat City, Menufyia Governerate, Egypt.

miRNAs are noncoding RNA that play a critical role as fine regulators of gene expression at the posttranscriptional level within cells in numerous autoimmune diseases. miR-221/222 play a role in cancer by regulating cell proliferation, invasion and apoptosis. However, there have been insufficient studies on their role in rheumatoid arthritis (RA). This work is designed to analyze the miR-221/222 expression patterns in peripheral blood mononuclear cells (PBMCs) of patients with RA in comparison with healthy controls using quantitative RT-PCR, in a group of 30 RA patients and 20 healthy controls. The fold change of miR-221/222 expression in PBMCs was significantly elevated (p < 0.01) in RA patients compared with healthy controls. A positive correlation between expression levels of miR-221 and miR-222 was recorded (r = 0.303; p < 0.05). High miR-221/222 expression levels appeared to be elevated with high activity. miR-222 expression in high activity group of RA patients was significantly increased in relation to moderate (p < 0.01) and low (p < 0.001) activity ones with positive correlation (r = 0.363; p < 0.05) between the progress of disease activity and change in miR-222 expression level. ROC analysis showed a sensitivity of 70% and specificity of 75% for miR-221. In miR-222, the sensitivity of 80% and specificity of 70% were recorded. Our data shed some light on the role of miR-221/222 expression in RA patients, and their great potential value as new novel noninvasive biomarkers for disease detection. Therefore; further investigations are warranted to fully elucidate their role in rheumatoid.
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http://dx.doi.org/10.1007/s10238-018-0524-3DOI Listing
February 2019

Association of TNF-Alpha gene polymorphisms and susceptibility to hepatitis B virus infection in Egyptians.

Hum Immunol 2017 Nov 18;78(11-12):739-746. Epub 2017 Oct 18.

Bioinformatics Department, Genetic Engineering and Biotechnology Research Institute (GEBRI), University of Sadat City, Egypt.

Tumor necrosis factor alpha (TNF-α) is one of the important cytokine in generating an immune response against hepatitis B virus (HBV). Genetic polymorphisms might influence gene transcription, leading to disturbance in cytokine production. We hypothesized that single nucleotide polymorphism (SNPs) in TNF-α gene could affect the pathogenesis of HBV. To test this hypothesis, we investigated the role of TNF-α polymorphism [-863C/A (rs1800630), -308G/A (rs1800629), -376G/A (rs1800750), -857C/T (rs1799724) and +489G/A (rs1800610)] in the susceptibility to chronic hepatitis B (CHB) infection. Polymorphisms of the TNF-α (-863C/A (rs1800630), -308G/A) were analyzed by Polymerase chain reaction sequence specific primer (PCR-SSP) while TNF-α (-376G/A, -857C/T and +489G/A) by PCR-restriction fragment length polymorphism (PCR-RFLP) in 104 patients with CHB and 104 healthy controls. The plasma level of TNF-α was measured using Enzyme-linked immunosorbent assay (ELISA). The study showed a significant increase in the frequency of -863CC, -376GA, -857CC, -857TT and +489GA genotypes and -863C, -376A, -857C, and +489A alleles in CHB patients compared to controls. In addition, CAGCG haplotype had a highest frequency in CHB patients. A strong Linkage Disequilibrium (LD) between TNF-α -863C/A (rs1800630) and -376G/A (D' = 0.7888, r = 0.0200); -308G/A and -857C/T (D' = 0.9213, r = 0.1770); -308G/A and +489G/A (D' = 0.9088, r = 0.1576) was demonstrated. CHB patients had significantly lower levels of TNF-α compared to controls. In conclusion, our preliminary results suggest that -863C/A (rs1800630), -308G/A, -376G/A, and +489G/A of the TNF-α gene may play a role in HBV susceptibility in Egyptians. The significant reduction in TNF-α in CHB patient was independent of any particular genotype/haplotype in TNF-α.
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http://dx.doi.org/10.1016/j.humimm.2017.10.006DOI Listing
November 2017

Hepatitis C Virus Associations with Non Hodgkin's Lymphoma: Insights on Inflammation/Angiogenesis and CD Markers.

Asian Pac J Cancer Prev 2016 ;17(9):4415-4420

Molecular Biology Department, Genetic Engineering and Biotechnology Research Institute (GEBRI), University of Sadat City, Egypt E-mail :

We aimed to investigate any association between hepatitis C virus (HCV) infection and non-Hodgkin’s lymphoma (NHL) in the view of cytokines that control inflammation/angiogenesis and their correlation with certain CD markers. NHL patients with or without HCV infection were studied. CD5, CD30, CD3, CD20 and CD45 were immunohistochemically evaluated. Plasma levels of vascular endothelial and platelet derived growth factors (VEGF, and PDGF), tumor necrosis factor (TNF-α), transforming growth factor (TGF-β), interleukin-6 (IL-6), IL-8, IL-4, IL-12 and interferon gamma (IFN-γ) were detected by enzyme-linked immunosorbent assay (ELISA). HCV+ve NHL patients showed a significant reduction in VEGF, PDGF, IFN-γ, CD5 and CD45 and a significant increase in IL-12 and IL-8. In conclusion, there was a significant change in cytokine secretion and expression of CD markers in HCV+ve NHL patients. Based on our results, HCV infection in NHL patients requires more in-depth investigations to explore any role in lymphoma progression.
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February 2017

Interleukin 10 (- 1082 G/A) and (- 819 C/T) gene polymorphisms in Egyptian women with polycystic ovary syndrome (PCOS).

Meta Gene 2016 Sep 3;9:254-8. Epub 2016 Aug 3.

Molecular Biology Department, Genetic Engineering and Biotechnology Research Institute (GEBRI), University of Sadat City, Egypt.

Cytokines play critical roles in the pathogenesis of Polycystic Ovarian Syndrome (PCOS). This work was designed to study the implication of IL10 gene polymorphisms (- 1082 G/A and - 819 C/T) on the susceptibility of Egyptian women to have PCOS. Rotterdam consensus criteria were used to diagnose PCOS patients. Genotyping was performed by single-stranded polymorphism-polymerase chain reaction (SSP-PCR) in 61 PCOS patients and 80 healthy controls, and IL-10 serum levels were measured using Enzyme linked immunosorbent assay (ELISA). The frequency of IL10 - 1082 G/G (46%) genotype was significantly increased (p < 0.001) while the frequency of - 1082 A/A (16%) genotype was significantly decreased (p < 0.05) in PCOS patients compared to controls (14% and 35% for G/G and A/A genotypes; respectively). G allele (65%) is significantly increased (p < 0.01( in PCOS patients while A allele (61%) is significantly increased (p < 0.001( in control subjects. The distribution of IL10 -819 T/T genotype was significantly increased (p < 0.05) in PCOS group. G/G genotype (odd ratio (OR = 5.322) with confidence interval (CI = 2.364-11.982) and the G allele (OR = 2.828 with CI = 1.73-4.61) of - 1082 G/A and T/T genotype of - 819 C/T (OR = 4.18 with CI = 1.26-13.86) could be considered as risk factors for PCOS. IL-10 levels were significantly lower among PCOS patients (313.42 ± 30.10) compared to normal controls (4914.36 ± 303.72). Depending on our preliminary work, IL10 - 1082 G/G might be considered as a host genetic factor for PCOS susceptibility in Egyptian women. Studies concerning other cytokine gene polymorphisms are required to get a better understanding of the pathogenesis of PCOS disease.
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http://dx.doi.org/10.1016/j.mgene.2016.08.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5006121PMC
September 2016

Correlation between angiogenic/inflammatory mediators in Wister rat model of liver dysplasia.

J Immunoassay Immunochem 2016 ;37(5):472-84

a Molecular Biology Department , Genetic Engineering and Biotechnology Research Institute (GEBRI), University of Sadat City , El Sadat , Egypt.

Angiogenesis plays a critical role in tumor development and progression. It is regulated through the elaboration of many inflammatory/angiogenic mediators. In this study, we followed angiogenesis in hepatocarcinogenesis process from cancer initiation to sever dysplasia by measuring several inflammatory/angiogenic mediators. Wister rat model of liver cancer was set up using diethylnitrosamine (DEN). One hundred twenty rats were divided into 7 groups: normal untreated and 1- to 6-month DEN-treated animals. Every month, group of DEN-treated animals were sacrificed. Histopathological examination of livers was done. Plasma levels of vascular endothelial and platelet derived growth factors (VEGF and PDGF), interleukin-8 (IL-8), IL-4, tumor necrosis factor (TNF-α), and cyclooxygenase-2 (COX-2) were quantified by enzyme-linked immunosorbent assay (ELISA). Histopathological findings were confirmatory to the gradual formation of liver cancer with time (from mild to moderate to irreversible severe dysplasia). Increase in angiogenic (VEGF and IL-8) (P < 0.001) and inflammatory (IL-4 and COX-2) (P < 0.001) mediators were observed. Elevation in TNF-α and PDGF secretion levels was recorded after 3 months of DEN injection (P < 0.001). Our data stressed on the importance of inflammation/angiogenesis processes in dysplasia. The exact regulatory mechanisms of liver cancer remain to be clarified.
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http://dx.doi.org/10.1080/15321819.2016.1157490DOI Listing
May 2017

Anti-inflammatory activity of green versus black tea aqueous extract in a rat model of human rheumatoid arthritis.

Int J Rheum Dis 2017 Feb 12;20(2):203-213. Epub 2015 May 12.

Zoology Department, Faculty of Science, Ain Shams University, Cairo, Egypt.

Aim: Recently, there has been an increasing interest in tea (Camellia sinensis) as a protective agent against inflammatory diseases. Here, we evaluated/compared the anti-inflammatory activity of two different doses (0.5 and 1.0 g/kg body weight) of green tea aqueous extract (GTE, rich in catechins) and black tea aqueous extract (BTE, rich in theaflavins and thearubigins) in rat adjuvant-induced arthritis (AIA).

Methods: Adjuvant-induced arthritis rat model received orally/daily distilled water as vehicle, indomethacin (1.0 mg/kg body weight; a non-steroidal/anti-inflammatory drug), or tea aqueous extracts (for 28 or 14 consecutive days starting from day 0 or 14 of arthritis induction, respectively).

Results: The present study showed that only the high dose of GTE (from day 0) significantly alleviated (P < 0.05-0.001) all complications shown in arthritic rats, including synovial joint inflammation, elevation in erythrocyte sedimentation rate, blood leukocytosis (due to lymphocytosis and neutrocytosis), and changes in weight/cellularity of lymphoid organs. The anti-arthritic activity of the high dose of GTE (from day 0) was comparable (P > 0.05) with that of indomethacin (12.9-53.8 vs. 9.5-48.4%, respectively) and mediated by significantly decreasing and down-regulating (P < 0.001) the systemic production of pro-inflammatory cytokines and the expression of chemokine receptor-5 in synovial tissues, respectively. Moreover, the anti-arthritic activity of tea aqueous extracts was in the following order: high dose of GTE > low dose of GTE ≥ high dose of BTE > low dose of BTE.

Conclusion: The present study proved the anti-inflammatory activity of GTE over BTE and equal to that of indomethacin in AIA rat model.
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http://dx.doi.org/10.1111/1756-185X.12666DOI Listing
February 2017

Effect of bisphosphonates treatment on cytokine imbalance between TH17 and Treg in osteoporosis.

Inflammopharmacology 2015 Jun 25;23(2-3):119-25. Epub 2015 Apr 25.

Molecular Biology Department, Genetic Engineering and Biotechnology Research Institute (GEBRI), Sadat City University, Sadat City, Egypt,

Imbalance of T-helper-cell (TH) subsets (TH1/TH2/TH17) and regulatory T cells (Tregs) is suggested to contribute to the pathogenesis of osteoporosis. Broken TH17/Treg balance has been reported contributing to several inflammatory diseases. Although bisphosphonates are well-recognized inhibitors of osteoclastic activity, there is no serious examination of their effect on T cell subset (TH1/TH2/TH17/Treg) balances. Patients were categorized into 20 osteopenic and 20 osteoporotic patients treated with bisphosphonates for 1 year. We studied plasma levels of interleukins 4 (IL-4), IL-6, IL-10, IL-12, IL-17, IL-23, and interferon-gamma (IFN-γ), and transforming growth factor-beta (TGF-β) and their interrelations and correlation with osteoporosis treatment were evaluated. Treated osteoporotic patients have a significant reduction of plasma IL-6 (p < 0.05), IL-17 (p < 0.05), IL-23 (p < 0.05), and IFN-γ (p < 0.05), a significant increase in IL-4 (p < 0.05), IL-10 (p < 0.05), and TGF-β (p < 0.001), and comparable IL-12 levels as compared to controls. In conclusion, the significant reduction of Th17 cell cytokine cascade (IL-6, IL-17, and IL-23) and elevation of Treg cytokine cascade (IL-10 and TGF-β) might be considered as a very important observation about the effect of bisphosphonates on TH17/Treg imbalance in osteoporosis.
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http://dx.doi.org/10.1007/s10787-015-0233-4DOI Listing
June 2015

Th1/Th2/Th17/Treg cytokine imbalance in systemic lupus erythematosus (SLE) patients: Correlation with disease activity.

Cytokine 2015 Apr 31;72(2):146-53. Epub 2015 Jan 31.

Biochemistry Department, National Liver Institute (NLI), Menofia University, Egypt.

Aim: Imbalance of T-helper-cell (TH) subsets (TH1/TH2/TH17) and regulatory T-cells (Tregs) is suggested to contribute to the pathogenesis of Systemic lupus erythematosus (SLE). Therefore, we evaluated their cytokine secretion profile in SLE patients and their possible association with disease activity.

Methods: Sixty SLE patients, 24 rheumatoid arthritis (RA) patients and 24 healthy volunteers were included in this study. Demographic, clinical, disease activity and serological data were prospectively assessed. Plasma cytokines levels of TH1 (IL-12, IFN-γ), TH2 (IL-4, IL-6, IL-10), TH17 (IL-17, IL-23) and Treg (IL-10 and TGF-β) were measured by enzyme linked immunosorbent assays (ELISA).

Results: SLE patients were found to have significantly higher levels of IL-17 (p<0.001), IL-6 (p<0.01), IL-12 (p<0.001) and IL-10 (p<0.05) but comparable levels of IL-23 and IL-4 and slight reduction (but statistically insignificant) of TGF-β levels compared to controls. IL-6, IL-10 and IL-17 were significantly increased (p<0.05) with disease activity. The RA group exhibited significantly higher levels of plasma IL-4 (p<0.01), IL-6 (p<0.05), IL-17 (p<0.001), IL-23 (p<0.01) and TGF-β (p<0.5) and lower IFN-γ (p<0.001) and IL-10 (p<0.01) than those of healthy subjects.

Conclusion: Our study showed a distinct profile of cytokine imbalance in SLE patients. Reduction in IFN-γ (TH1) and TGF-β1 (Treg) with the elevation in IL-6 and IL-17 (TH17) could imply skewing of T-cells toward TH17 cells. Breaking TH17/Treg balance in peripheral blood may play an important role in the development of SLE and could be responsible for an increased pro-inflammatory response especially in the active form of the disease.
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http://dx.doi.org/10.1016/j.cyto.2014.12.027DOI Listing
April 2015

CD38 and interleukin 6 gene polymorphism in egyptians with diffuse large B-cell lymphoma (DLBCL).

Immunol Invest 2015 7;44(3):265-78. Epub 2015 Jan 7.

Molecular Biology Department, Genetic Engineering and Biotechnology Research Institute (GEBRI), Sadat City University , Egypt and.

Given the importance of understanding the genetic variations involved in the pathogenesis of non-Hodgkin's lymphoma (NHL), this pilot study was designed to investigate the impact of CD38 (184C/G; rs6449182) and IL-6 (-174 G/C; rs1800795) gene polymorphism on susceptibility of Egyptians to diffuse large B cell lymphoma (DLBCL); major types of NHL. To the best of our knowledge, this study is the first one that examines CD38 polymorphism in the NHL. Genotyping polymorphism is performed using restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) for CD38 and Mutagenically separated PCR (MS-PCR) for IL-6 in 100 Egyptian NHL patients with DLBCL subtype and 119 normal controls. The serum level of IL-6 was measured using Enzyme-linked immunosorbent assay (ELISA). CD38 (184C/G) genotype is significantly increased in NHL patients (p < 0.01), while the GG genotype is significantly increased in controls (p < 0.05). Only two genotypes were found (GG and GC) in IL-6 (-174), no CC in our NHL patients and only one case in the controls. Insignificant change in IL-6 (-174 G/C) genotypes was recorded. Significantly increased serum IL-6 (p < 0.05) was positively correlated (r = 0.17; p < 0.05) with the disease. Taken together, our data stressed the importance of CD38 gene polymorphism in developing DLBCL. Our pilot study indicates that CD38 (184) CG genotype might play a role in DLBCL susceptibility in Egyptians. Additional prospective studies on larger population are needed to confirm our findings.
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http://dx.doi.org/10.3109/08820139.2014.989328DOI Listing
January 2016

Synthesis and evaluation of thalidomide and phthalimide esters as antitumor agents.

Arch Pharm (Weinheim) 2014 Sep 18;347(9):642-9. Epub 2014 Jun 18.

Faculty of Science, Department of Chemistry, Menoufia University, Shebin El-Koam, Egypt.

A series of thalidomide and phthalimide ester analogs were efficiently synthesized from N-chloromethylthalidomide, N-chloromethylphthalimide, and N-(2-bromoethyl)phthalimide derivatives with various biologically important carboxylic acids. The synthesized compounds were purified and characterized by various chromatographic and spectroscopic techniques. The antitumor activity of all the synthesized compounds was screened against human liver and breast cancer cells, which showed that phthalimide ester 6a was the best cytotoxic compound against MCF7 cells, while all of the tested compounds showed a non-cytotoxic effect against HepG2 cells. Compounds 5a, 6a, and 7a possess immunosuppressant effect, while compounds 5c, 5d, 6c, 6d, 7c, and 7d showed an immunostimmulatory effect. Meanwhile, estimation of the binding affinity for all the synthesized compounds toward the vascular endothelial growth factor receptor (VEGFR) showed that compounds 5a, 5b, and 7d were the most potent inhibitors.
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http://dx.doi.org/10.1002/ardp.201400073DOI Listing
September 2014

Association between IL-10 gene promoter polymorphism and hepatitis B viral infection in an Egyptian population.

Biochem Genet 2014 Oct 17;52(9-10):387-402. Epub 2014 May 17.

Molecular Biology Department, Genetic Engineering and Biotechnology Research Institute, University of Sadat City, Sadat City, Egypt,

Cytokines play critical roles in the pathogenesis of hepatitis B virus infection (HBV). This work was designed to study the effect of IL-10 gene polymorphisms (-1082G/A and -819C/T) on susceptibility of Egyptians to HBV. Genotyping was performed using single-stranded polymorphism-polymerase chain reaction in 118 Egyptian hepatitis B patients and 119 healthy controls, and IL-10 serum levels were measured using ELISA. The frequency of IL-10 -1082G/G was significantly higher in HBV patients than in healthy controls, and G/A and A/A were not significantly different between groups. The distribution of IL-10 -819 genotypes was not significantly different between the HBV and healthy control groups. Although AT was significantly different between controls and patients, the distribution of the other haplotypes was not. IL-10 levels were significantly lower among hepatitis B patients. Our data stress the importance of IL-10 gene polymorphism in HBV infection. Depending on our preliminary work, IL-10 -1082G/G may act as a host genetic factor in the susceptibility to HBV infection in Egyptians.
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http://dx.doi.org/10.1007/s10528-014-9655-8DOI Listing
October 2014

Polymorphisms of interleukin 6 and interleukin 10 in Egyptian people with Behcet's disease.

Immunobiology 2014 Aug 20;219(8):573-82. Epub 2014 Mar 20.

National Liver Institute (NLI), Menufia University, Egypt.

Cytokines play critical roles in the pathogenesis of Behçet's disease (BD). They mediated many of the effectors and regulatory functions of immune and inflammatory responses. Many studies have linked Interleukin-6 (IL-6) and Interleukin-10 (IL-10) pathologically to BD. Thus, this study aimed to investigate the associations between IL-6 and IL-10 promoter single-nucleotide polymorphisms (SNPs) and the susceptibility to BD and their implication on plasma levels. We genotyped IL-6 -174 G/C (rs1800795) using Mutagenically Separated Polymerase Chain Reaction PCR (MS-PCR) and IL-10 -1082 G/A (rs1800896) and -819 C/T (rs1800871) using Sequence Specific Primer PCR (SSP-PCR) in 87 Egyptian patients and 97 controls. The plasma levels of IL-6 and IL-10 were measured using Enzyme-linked Immunosorbent Assay (ELISA). Significant increase in the frequency of -1082 GG genotype (P<0.05, OR=2.25, 95%CI=1.03-4.91) and significant decrease in the frequency of -1082 GA genotype (P<0.05, OR=0.53, 95%CI=0.29-0.96) was demonstrated in BD patients compare to controls. Patients with genital ulcer had significantly lower frequency of -1082 GG (P<0.05, OR 0.2, 95% CI=0.04-0.99) and G allele (P<0.05, OR=0.28, 95%CI=0.08-0.93), while patients with ocular manifestations had significantly higher frequency of -1082 G allele (P<0.01, OR=2.28, 95%CI=1.19-4.36). BD patients had significantly higher level of IL-6 (P<0.001) and significantly lower level of IL-10 (P<0.001) compared to controls. The changes in the level of cytokines were independent of any genotype of IL-6 or any genotype/haplotype of IL-10. Patients with active disease state had significantly higher level of IL-6 compared to patients in remission (P<0.05). In conclusion, our preliminary study indicates that the polymorphism at IL-10 -1082 G/A may play a role in BD susceptibility. The significant increase in IL-6 level and the significant decrease in IL-10 level in BD patients were independent of any particular genotype in IL-6 or any particular genotype/haplotype in IL-10.
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http://dx.doi.org/10.1016/j.imbio.2014.03.004DOI Listing
August 2014

Circulating pro- and anti-angiogenic mediators in patients infected with hepatitis C at different stages of hepatocellular carcinoma.

J Med Virol 2014 Jul 28;86(7):1120-9. Epub 2014 Mar 28.

Molecular Biology Department, Genetic Engineering and Biotechnology Research Institute (GEBRI), Sadat City University, Sadat City, Egypt.

Hepatocellular carcinoma (HCC) is a hypervascular tumor characterized by neovascularization. The objective of the current study was to determine circulating proangiogenic [vascular endothelial growth factor (VEGF), platelet derived growth factor (PDGF), and tumor necrosis factor (TNF-α)] and antiangiogenic [IL-4, IL-12, interferon gamma-induced protein 10 (IP-10), and angiostatin] factors in Egyptian patients with different stages of HCC. Enzyme-linked immunosorbent assay (ELISA) was used to detect the concentrations of these mediators in plasma of 135 HCC patients (57 Child-Pugh A, 24 Child-Pugh B, and 54 Child-Pugh C stage) and 50 healthy subjects. Results showed a significant increase in plasma levels of VEGF (P < 0.001), PDGF (P < 0.001), TNF-α (P < 0.01), angiostatin (P < 0.01), and IP-10 (P < 0.001) and a significant reduction in IL-12 (P < 0.001) in HCC patients in relation to normal controls. Classifying HCC patients based on their Child-Pugh's score revealed that the maximum production of proangiogenic mediators (VEGF and TNF-α) was present in HCC patients with Child-Pugh C score which coincides with maximum reduction in antiangiogenic mediators (IL-4, IL-12, and angiostatin). Taken together, these results indicated that the determination of these factors in different Child-Pugh's scores of HCC might be an important guide in clinical decision making regarding therapy and outcome.
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http://dx.doi.org/10.1002/jmv.23932DOI Listing
July 2014

Autoantibodies against complement C1q in patients with Behcet's disease: association with vascular involvement.

Mod Rheumatol 2014 Mar;24(2):316-20

Department of Rheumatology and Rehabilitation, Faculty of Medicine, Cairo University, El-Kasr El-Aini Hospital , Cairo , Egypt.

Aim: The aim of our study was to determine the prevalence of anti-C1q antibodies and their possible association with clinical presentation in Behcet's disease (BD) patients with special emphasis for patients with vascular involvement.

Methods: Plasma anti-C1q Abs levels were measured using an enzyme-linked immunosorbent assay in 51 BD patients and 25 age- and gender-matched healthy controls.

Results: We found elevated concentrations of anti-C1q more frequently in patients with BD (18 %) than in healthy controls (8 %). The highest prevalence was found in patients with vascular BD (42 %) which was significantly higher than patients without vascular BD and healthy controls (p = 0.025). Furthermore, patients with vascular BD had the highest mean anti-C1q levels when compared to BD patients without vascular involvement or healthy control subjects (p = 0.015). We did not find significant differences in the prevalence of any other organ involvement between BD patients with elevated vs. normal anti-C1q ab levels. Anti-C1q ab levels positively correlated with ESR (r = 0.383, p = 0.006) and negatively with C4 (r = -0.304, p = 0.030).

Conclusion: In conclusion, we found an increased prevalence of anti-C1q autoantibodies in BD patients with vascular involvement. Further large scale longitudinal studies are required to assess and clarify the significance and the pathogenic role of anti-C1q antibodies in BD and other autoimmune diseases in which vasculitis is a component.
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http://dx.doi.org/10.3109/14397595.2013.854071DOI Listing
March 2014

Therapeutic effect of dimethyl dimethoxy biphenyl dicarboxylate on collagen-induced arthritis in rats.

Chin J Integr Med 2015 Nov 2;21(11):846-54. Epub 2014 Mar 2.

Pathology Department, Faculty of Medicine, Tanta University, Tanta, 31111, Egypt.

Objective: To study the effect of oral administration of dimethyl dimethoxy biphenyl dicarboxylate (DDB) on adjusting angiogeneic/inflammatory mediators and ameliorating the pathology of bones in rats with collagen-induced arthritis (CIA).

Methods: Wistar rat model of CIA was set up using bovine collagen type II. Fifty rats were divided into five groups randomly: normal, CIA model, DDB treatment, methotrexate (MTX) treatment, and combined DDB+MTX treatment. Ankle joints of rats were imaged with digital X-ray machine to show the destruction of joints. Fore and hind paw and knee joints were removed above the ankle joint then processed for haematoxylin and eosin staining. Plasma levels of vascular endothelial growth factor (VEGF), platelet derived growth factor, interleukin-8 (IL-8), IL-4, tumor necrosis factor α (TNF-α), and cyclooxygenase-2 (COX-2) were quantified by enzyme-linked immunosorbent assay. Nitric oxide levels were detected by Griess reagent.

Results: Compared with the CIA model group, a remarkable reduction in various angiogenic (VEGF and IL-8) and inflammatory mediators (TNF-α, IL-4 and COX-2) after treatment with DDB either alone or combined with MTX P<0.05 or P<0.01). Histopathological and X-ray findings were confirmatory to the observed DDB anti-arthritic effect. The DDB-treated group showed amelioration in signs of arthritis which appeared essentially similar to normal.

Conclusion: Our data shed light on the therapeutic efficacy of DDB in experimental rheumatoid arthritis (RA) compared with a choice drug (MTX) and it may be offered as a second-line drug in the treatment of RA.
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http://dx.doi.org/10.1007/s11655-014-1746-1DOI Listing
November 2015

Transforming Growth Factor- β 1 Gene Polymorphism (T29C) in Egyptian Patients with Hepatitis B Virus Infection: A Preliminary Study.

Hepat Res Treat 2013 18;2013:293274. Epub 2013 Dec 18.

Animal Biotechnology Department, Genetic Engineering and Biotechnology Research Institute (GEBRI), University of Sadat City, Sadat City 22857, Egypt.

The interindividual variations in the capacity of transforming growth factor- β 1 (TGF- β 1) production have been ascribed to genetic polymorphisms in TGF- β 1 gene. As pathogenesis of HBV has a genetic background, this preliminary study was designed to assess the impact of TGF- β 1 (T29C) on the susceptibility of Egyptians to HBV infection. Genotyping was performed using single stranded polymorphism-polymerase chain reaction (SSP-PCR) in 65 Egyptian hepatitis B patients and 50 healthy controls. TGF- β 1 plasma levels were measured using Enzyme-linked immunosorbent assay (ELISA). The frequency of CC genotype was significantly higher (P < 0.05) in HBV patients compared to controls. On the contrary, TC genotype did not show significant difference in both groups. TT genotype was significantly higher (P < 0.01) in controls than HBV patients. Our current preliminary data revealed that the frequency of the genotypes in the controls were within Hardy-Weinberg equilibrium (HWE) while the patients group was out of HWE (P < 0.01). TGF- β 1 was significantly (r = -0.684; P < 0.001) deceased in the sera of patients as compared to normal subjects. Depending on our preliminary work, CC genotype may act as a host genetic factor in the susceptibility to HBV infection in Egyptians. Taken together, the current data pointed to the importance of polymorphism of TGF- β 1 gene (T29C) in HBV infection.
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http://dx.doi.org/10.1155/2013/293274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3878635PMC
January 2014

Autoantibodies against complement C1q in patients with Behcet's disease: association with vascular involvement.

Mod Rheumatol 2013 Apr 7. Epub 2013 Apr 7.

Department of Rheumatology and Rehabilitation, Faculty of Medicine, Cairo University, El-Kasr El-Aini Hospital, Cairo, Egypt,

AIM: The aim of our study was to determine the prevalence of anti-C1q antibodies and their possible association with clinical presentation in Behcet's disease (BD) patients with special emphasis for patients with vascular involvement. METHODS: Plasma anti-C1q Abs levels were measured using an enzyme-linked immunosorbent assay in 51 BD patients and 25 age- and gender-matched healthy controls. RESULTS: We found elevated concentrations of anti-C1q more frequently in patients with BD (18 %) than in healthy controls (8 %). The highest prevalence was found in patients with vascular BD (42 %) which was significantly higher than patients without vascular BD and healthy controls (p = 0.025). Furthermore, patients with vascular BD had the highest mean anti-C1q levels when compared to BD patients without vascular involvement or healthy control subjects (p = 0.015). We did not find significant differences in the prevalence of any other organ involvement between BD patients with elevated vs. normal anti-C1q ab levels. Anti-C1q ab levels positively correlated with ESR (r = 0.383, p = 0.006) and negatively with C4 (r = -0.304, p = 0.030). CONCLUSION: In conclusion, we found an increased prevalence of anti-C1q autoantibodies in BD patients with vascular involvement. Further large scale longitudinal studies are required to assess and clarify the significance and the pathogenic role of anti-C1q antibodies in BD and other autoimmune diseases in which vasculitis is a component.
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http://dx.doi.org/10.1007/s10165-013-0880-5DOI Listing
April 2013

Gene polymorphism of transforming growth factor-β1 in Egyptian patients with type 2 diabetes and diabetic nephropathy.

Acta Biochim Biophys Sin (Shanghai) 2013 Apr 10;45(4):330-8. Epub 2013 Feb 10.

Molecular Immunology, Molecular Biology Department, Genetic Engineering and Biotechnology Research Institute (GEBRI), Menofia University, Menofia 22857, Egypt.

Role of the transforming growth factor-β1 (TGF-β1) gene polymorphisms located at codons 10 and 25 in the genetic predisposition to type 2 diabetes (T2D) and in diabetic nephropathy (DN) in Egyptian patients was investigated. A case control study was done for 99 unrelated Egyptian patients with T2D (50 DN(-) and 49 DN(+)) and 98 age- and sex-matched healthy controls. TGF-β1 T869C (codon 10) and G915C (codon 25) polymorphism detection was done by amplification refractory mutation system method. DN(+) patients were younger, with higher body mass index, serum triglycerides, serum creatinine, and lower serum albumin than those in DN(-) patients. Moderate and bad grades of diabetic control were associated with DN (P < 0.001). The TGF-β1 (T869C) C allele, TC and TC + CC genotypes were significantly higher in patients; the T allele and TT genotype were significantly higher in controls (Pc < 0.001). The TGF-β1 TC genotype was associated with DN (Pc < 0.05). Non-significant differences were detected between T2D patients and controls in the frequencies of TGF-β1 (G915C) alleles and genotypes. In conclusion, these preliminary data showed that the TGF-β1 codon 10 C allele, and C allele-containing genotypes may be susceptible, and T allele/TT genotype may be protective factors for T2D and DN(+) complications.
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http://dx.doi.org/10.1093/abbs/gmt003DOI Listing
April 2013