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

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.

Impacts of circulating cytokine levels and gene polymorphism predisposition on type 1 diabetes mellitus.

PURPOSE: A wide range of cytokines has been demonstrated to be involved in the etiology of type 1 diabetes mellitus (T1DM). Gene polymorphisms may potentially contribute to a hereditary predisposition toward circulating cytokine levels as (high, intermediate, or low) since they can affect cytokine production or function. The aim of this study was to investigate the roles of cytokine levels and the association of single-nucleotide polymorphisms (SNPs) within cytokine genes with T1DM in Saudi children. METHODS: Totals of 91 well-characterized T1DM patients and 91 T1DM-free control subjects were enrolled in this study. RESULTS: The levels of 3 circulating cytokines (transforming growth factor [TGF]-ß1, interleukin [IL]-10, and IL-6) and 6 SNPs in 3 cytokine genes (TGF-ß1 [rs1800470 and rs1800471], IL-10 [rs1800896, rs1800871, and rs1800872], and IL-6 [rs1800795]) that contribute to genetic susceptibility were measured by enzyme-linked immunosorbent assay and polymerase chain reaction with sequence-specific primers. Our fn dings show that TGF-ß1 serum levels were signifcantly lower in the children with T1DM than in the control participants. The TGF-ß1 genotypes with a high-production phenotype were signifcantly less frequent and those with a lowproduction phenotype were signifcantly more frequent in the children with T1DM compared to the control participants. respectively. Furthermore, the IL-6 genotype frequency with low level of IL-6 production were signifcantly increased in the T1DM group compared to the control group. Moreover, our data demonstrated no appreciable diferences in circulating serum level or genotype and phenotype of IL- 10 between the patients and controls. CONCLUSION: This kind of measurement, which considers the prediction of T1DM, may be useful in assessing the severity of T1DM and susceptibility to T1DM among Saudi children.

Gene polymorphism of transforming growth factor-ß1 in Egyptian patients with type 2 diabetes and diabetic nephropathy.

Role of the transforming growth factor-ß1 (TGF-ß1) 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-ß1 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-ß1 (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-ß1 TC genotype was associated with DN (Pc < 0.05). Non-significant differences were detected between T2D patients and controls in the frequencies of TGF-ß1 (G915C) alleles and genotypes. In conclusion, these preliminary data showed that the TGF-ß1 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.

Single nucleotide polymorphisms of interleukins associated with hepatitis C virus infection in Egypt.

INTRODUCTION: Hepatitis C is a liver disease caused by the hepatitis C virus (HCV). It can cause both acute and chronic hepatitis infection. Based on secretion of required cytokines upon infection, HCV can improve its own RNA and successfully complete the replication cycle. Importantly, single nucleotide polymorphisms (SNPs) are the most common type of genetic variation and have been found to play a critical role in modulation of cellular cytokine production and interaction. METHODOLOGY: A total of 100 blood samples were obtained from HCV patients, and 120 samples were obtained from healthy individuals who served as controls. SNPs of interleukin-10/592 (IL-10/592) and IL-4/589 were investigated for possible connection with HCV infection. Relative expression of IL-4, IL-6, and IL-10 were detected using real-time polymerase chain reaction and enzyme-linked immunosorbent assay. RESULTS: The polymorphisms of IL-10 revealed a high rate of mutant genotype CC within the location IL-10/592 in HCV patients and controls, which resulted in low secretion of IL-10. Interestingly, the findings here demonstrate a positive association between HCV load of viremia and the mutant genotype IL-4-589/TT accompanied with low expression IL-4 in comparison with IL-6 expression. CONCLUSIONS: These data suggest that the expression of IL-4 is inversely proportional to HCV load of viremia, and this connection is due to the high level of mutant genotype IL-4-589/TT in infected patients located in gene promoter and inhibits gene expression.

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

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-ß), 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.

Association of HLA-E polymorphism with severe bacterial infection and early transplant-related mortality in matched unrelated bone marrow transplantation.

Despite prophylactic measures, susceptibility to severe infections in patients who had undergone bone marrow transplantation (BMT) is quite variable. To evaluate the potential role of human leukocyte antigen (HLA)-E polymorphism on the incidence of early infections, we analyzed 77 unrelated-donor (UD) BMT pairs identically matched for classical HLA class I and class II alleles. Multivariate analysis taking into account the patient-, donor- and transplant-related factors showed that bacterial infections and transplant-related mortality (TRM) at day 180 were high when the donor genotype was HLA-E*0101/E*0101 (hazard ratio [HR]=2.20; P=0.03 and HR=2.12, P=0.048, respectively), suggesting that homozygous state for HLA-E*0101 allele is a risk factor for early severe bacterial infections and TRM in UD-BMT.

Impact of CD31 mismatches on the outcome of hematopoeitic stem cell transplant of HLA-identical sibling.

Graft-versus host disease (GVHD) complicating allogeneic hematopoeitic stem cell transplantation (HSCT) is often attributed to mismatching of minor histocompatibility antigens (mHags), which are poorly defined in humans. CD31 is a candidate human mHag relevant to acute GVHD (aGVHD), but reports disagree about its level of significance. Therefore, we examined the impact of CD31-matching on the outcome of HSCT in different hematological and immunological diseases. About 60 patients receiving HSC from their respective HLA-ABCDR and DQ-identical sibling were studied. DNA was used to study the CD31 allele polymorphism at the codon 125 (LL, LV or VV) in the patient-donor pairs using the principle of allele-specific PCR amplification. Four primer were used; two primers (forward and reverse) for the L allele and another two for the V allele. The CD31 identity was tested for correlation with HSCT outcome measures of aGVHD, chronic GVHD, and relapse. The gene frequency of CD31 alleles (LL, VV and LV) was 28.3, 20 and 51.7%, respectively. CD31 identity was found in 31 pairs (51.7%) versus 29 pairs (48.3%) for nonidentity. The CD31 noncompatibility showed statistical non-significant relation with aGVHD (G 0-I, and G II-IV) and chronic GVHD (De-novo and chronic on acute) (p = 0.59, p = 0.62, p = 036 and p = 0.83, respectively). The CD31 nonidentity had statistical significant relation with aGVHD versus no aGVHD (p = 0.008 and OR = 4.46). The CD31 nonidentity showed statistical significant relation with aGVHD (II-IV) versus no aGVHD (p = 0.012 and OR = 7.14) and also, aGVHD (0-I) versus the no aGVHD (p = 0.03, OR = 3.13, respectively). A statistical significant relation was found between CD31 nonidentity in patient-donor pairs and relapse (p = 0.014 and OR = 4.21). In conclusion, the donor-recipient CD31 nonidentity is a significant risk factor for aGVHD and relapse in HLA-identical sibling.