FOXP3 Polymorphism and Susceptibility to Pediatric Acute Lymphocytic Leukemia (ALL): A Preliminary Data

FOXP3 (forkhead box P3) polymorphism is associated with many inflammatory diseases and cancers. Acute lymphoblastic leukemia (ALL) is the most common type of pediatric malignancies.This study was designed to investigate the impact of FOXP3 (-3279C/A and -2383C/T) gene polymorphism on the susceptibility of Egyptian children to ALL. A total of 128 subjects with ALL and 124 healthy controls were enrolled in this study. Genotyping of FOXP3 (-3279C/A and -2383C/T) were performed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). There was a significant increase (P<0.01) in FOXP3 (-3279CC) genotype, while FOXP3 -3279CA genotype was significantly decreased in ALL patients compared to controls. Insignificant change in FOXP3 (-2383C/T) genotypes was demonstrated between both groups. FOXP3 (-2383CC) genotype was significantly decreased (p<0.05) in treatment responders compared to non-responders and a significant increased (p<0.05) in relapsed patients comparing to the non-relapsed group. Taken together, our pilot study pointed to the potential role of FOXP3 (-3279C/A) gene polymorphisms in Egyptian children ALL susceptibility. An additional prospective large scale study should be carried out to support our findings

Clinical significance of anti-cyclic citrullinated peptide antibodies in Egyptian patients with chronic hepatitis C virus genotype IV infection

Background: Symmetric polyarthritis associated with hepatitis C virus (HCV) infection frequently displays a clinical picture like rheumatoid arthritis (RA). Antibodies to cyclic citrullinated peptide (CCP) have high specificity for the diagnosis of RA. This study examined the frequency and clinical significance of anti-CCP antibodies in patients with chronic HCV infection, with and without manifestations of joint involvement, compared to RA patients. Methods: Serum anti-CCP antibodies and rheumatoid factor (RF) were evaluated in 30 patients with RA and 47 patients with chronic HCV infection. Of those with HCV infection, 20 patients had chronic HCV infection associated with articular involvement and 27 patients had chronic HCV infection without any articular involvement. Results: Anti-CCP antibody level was positive in 70% of RA patients, 8.5% of HCV-infected patients, and in 20% of HCV patients with articular manifestations. RF was positive in 76% of RA patients and in 60% of HCV patients with articular involvement. Cryoglobulins were found in 29% of HCV-infected patients and in 16% of RA patients. Cryoglobulins were more frequent among HCV patients with articular affection (35%) compared to HCV patients without articular affection (26%). Conclusions: Although anti-CCP antibodies remain a useful diagnostic tool for RA, their interpretation in HCV-infected patients with arthritis should be applied with caution. The possibility that those patients could be prone to develop RA cannot be ruled out. Those patients need careful clinical and radiological follow-up. Further large-scale studies are warranted. Clin Chem Lab Med 2009;47:842–7.Peer Reviewe

Cytotoxic effect of combining two antisense oligonucleotides against telomerase rna component (hTR and mRNA of centromere protein B (CENP-B) in hepatocellular carcinoma cells

Abstract Telomerase is a ribonucleoprotein enzyme that plays a crucial role in maintaining the malignancy and is responsible for cellular immortality and tumorigenesis. On another hand, Centromere protein B (CENP-B) plays an important role in cell cycle regulation and helping in the high rate proliferation of cancer cells. Our study is designed to evaluate the effect of using combined antisense oligonucleotides (ASOs) targeting (hTR) and mRNA of CENP-B on liver cancer cells. Compared with a single treatment, combination treatment with Locked Nucleic Acid (LNA) ASO (hTR) and (CENP-B) (6.25 nM from each) exhibit the maximum synergistic cytotoxic effect. hTR and CENP-B mRNA was abrogated while hTERT expression was disappeared. Caspase-3, Bax, and Bcl-2 were not detected, indicating caspase-independent cell death. A significant reduction in [Tumor necrosis factor (TNF-α) and Transforming growth factor (TGF-β)] coincides with elevation in Nitric oxide (NO) secretions was observed. Taken together; our data suggest that combination treatment with LNA ASO (hTR) and (CENP-B) could provide a promising strategy for cancer treatment by controlling many pathways concurrently. This might open a new prospective application of antisense in cancer therapy

Interleukin 10 gene promoter polymorphism and risk of diffuse large B cell lymphoma (DLBCL)

Purpose: Given the importance of understanding the genetic variations involved in the pathogenesis of non-Hodgkin’s lymphoma (NHL), this work was designed to study the impact of IL-10 (−1082 G/A; rs1800896 and −819 C/T; rs1800871) gene promoter polymorphism on susceptibility of Egyptians to diffuse large B cell lymphoma (DLBCL); the major type of NHL. To the best of our knowledge, this study is the first one that examines IL-10 promoter polymorphism in DLBCL in Egyptians. Methods: Genotyping polymorphism is performed using sequence-specific primers polymerase chain reaction (SSP-PCR) in 100 Egyptian DLBCL patients and 119 normal controls. Circulating plasma levels of IL-10 were measured using Enzyme-linked immunosorbent assay (ELISA). Results: Insignificant change in IL-10 (−1082 and −819) genotypes was recorded. Although A allele is slightly decreased in DLBCL patients, it did not reach statistical significance. GT haplotype was significantly elevated (P < 0.05) in NHL patients. A significant linkage disequilibrium between the −1082 and −819 SNPs with D′ = 0.596 and r2 = 0.1032 (P < 0.001) was demonstrated. Significantly increased plasma IL-10 (P < 0.01) was found which is positively correlated (r = 0.307; P < 0.01) with the disease. Conclusions: Taken together, our findings demonstrated that IL-10 promoter gene polymorphism (−1082 and −819) may not have an influence on the clinical outcome of DLBCL, especially in terms of overall secretion level. Further investigations of other cytokine gene polymorphisms will lead to a better understanding of the disease’s biological background

Alleviative effects of green and black tea aqueous extracts on cellular oxidative stress and anemia in rat adjuvant-induced arthritis

335-343The aim of this study was to evaluate and compare the alleviative effects of two doses (0.5 and 1.0 gm/kg body weight) of green and black tea aqueous extracts (GTE and BTE, <span style="font-size: 9.0pt;mso-fareast-font-family:Calibri" lang="EN-US">respectively) on articular/extra-articular complications in rat adjuvant-induced arthritis (AIA). Arthritic rats received distilled water as vehicle, indomethacin (1.0 mg/kg body weight; a non-steroidal/anti-inflammatory drug), or tea aqueous extracts orally/daily for 28 days started from the day <span style="font-size:9.0pt; mso-fareast-font-family:Calibri" lang="EN-US">of arthritis induction (day 0). Other arthritic rats received tea aqueous extracts <span style="font-size:9.0pt;mso-fareast-font-family: Calibri" lang="EN-US">orally/daily for 14 days started from the day of arthritis onset (day 15). Both tea aqueous extracts significantly suppressed (but with different degrees) the arthritis severity/complications in AIA rat model especially at the high dose and when the treatment started from day 0. Only the high dose of GTE (from day 0) <span style="font-size:9.0pt;mso-fareast-font-family: Calibri" lang="EN-US">significantly alleviated, as indomethacin (53.32 <span style="font-size:9.0pt; font-family:Symbol;mso-ascii-font-family:" times="" new="" roman";mso-hansi-font-family:="" "times="" roman";mso-char-type:symbol;mso-symbol-font-family:symbol"="" lang="EN-US">± 15.41 and 48.35 ± 17.09, respectively), all complications shown in arthritic rats including body weight loss, anemia, arthritic score, and synovial/hepatic tissues lipid peroxidation (P<0.05-0.001) through significantly increasing food intake (P<0.001) and cellular antioxidants (P<0.05-0.001): reduced glutathione level and catalase, glutathione peroxidase and superoxide dismutase activities. Therefore, tea (especially green tea) may be useful in the management of rheumatoid arthritis complications. </span

Therapeutic outcomes and biodistribution of gold nanoparticles in collagen-induced arthritis animal model

The role of gold nanoparticles (AuNPs) in the treatment of autoimmune diseases remains mysterious. Therefore, we investigated the effect of AuNPs on collagen-induced arthritis (CIA) and the impact of particle size on the tissue distribution of AuNPs. CIA model was set up in Wistar rats using bovine collagen type ІІ. CIA rats were then divided into five groups: CIA model (positive control), AuNPs treated- (sphere shape with size: 5, 25, and 75 nm), and methotrexate (MTX)-treated-rats. Untreated rats were run in parallel as normal control. At the end of the experiment, the radiographic assessment was done. Histopathological changes in the joints and vital organs were investigated. Liver- [aspartate transaminase (AST) and alanine transaminase (ALT)] and kidney- (creatinine) functions were measured. The gold bio-accumulation was measured quantitatively with inductively coupled plasma mass spectrometry (ICP-MS). Histopathological results revealed that AuNPs reduced the severity of arthritic symptoms in CIA rats. No histological changes were detected in vital organs. Importantly, AuNPs were deposited in all the examined organs, and the accumulation was size-dependent, with 75 nm demonstrated the least distributed one. Our results revealed that AuNPs decreased both liver and kidney functions as compared to normal controls. In conclusion, our data shed light on the therapeutic efficacy of AuNPs in experimental rheumatoid arthritis compared with a choice size (25 nm). Further investigations to investigate the immunological changes associated with AuNPs are in process.This work was funded by the Science and Technology Development Fund (STDF), Egyptian Academy of Scientific Research and Technology (ASRT), Egypt (Grant No. 22996), and the Jordan Scientific Research Support Fund (SRSF), Jordan (Grant no. Egy-Jor/March 1, 2015)