Early diagnostic evaluation of miR-122 and miR-224 as biomarkers for hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is one of the common lethal types of tumor all over the world.The lethality of HCC accounts for many reasons.One of them,the lack of reliable diagnostic markers at the early stage,in this context,serum miRNAs became promising diagnostic biomarkers.Herein,we aimed to identify the predictive value of two miRNAs(miR-122 and miR-224)in plasma of patients with HCC preceded by chronic HCV infection.Taqman miRNA assays specific for hsa-miR-122 and hsa-miR-224 were used to assess the expression levels of the chosen miRNAs in plasma samples collected from three groups;40 patients with HCC related to HCV,40 with CHC patients and 20 healthy volunteers.This study revealed that the mean plasma values of miRNA-122 were significantly lower among HCC group when compared to CHC and control groups(P<0.001).Whereas,miR-224 mean plasma values were significantly higher among HCC group when compared to both CHC group and control group.Moreover,it was found that miR-122 can predict development of HCC at cut-off value<0.67(RQ)and(AUC Z 0.98,P<0.001).As regards miR-224,it can predict development of HCC at cut-off value>1.2(RQ)and(AUC Z 0.93,P<0.001),while the accuracy of AFP to diagnose HCC was(AUC:0.619;P Z 0.06).In conclusion,the expression plasma of miR-122 and miR-224 could be used as noninvasive biomarkers for the early prediction of developing HCC at the early stage.

An Integrative Meta-analysis of MicroRNAs in Hepatocellular Carcinoma

We aimed to shed new light on the roles of microRNAs （miRNAs） in liver cancer using an integrative in silico bioinformatics analysis. A new protocol for target prediction and functional analysis is presented and applied to the 26 highly differentially deregulated miRNAs in hepatocellular carcinoma. This framework comprises： （1） the overlap of prediction results by four out of five target prediction tools, including TargetScan, PicTar, miRanda, DIANA-microT and miRDB （combining machine-learning, alignment, interaction energy and statistical tests in order to minimize false positives）, （2） evidence from previous microarray analysis on the expression of these targets, （3） gene ontology （GO） and pathway enrichment analysis of the miRNA targets and their pathways and （4） linking these results to oncogenesis and cancer hallmarks. This yielded new insights into the roles of miRNAs in cancer hallmarks. Here we presented several key targets and hundreds of new targets that are significantly enriched in many new cancer-related hallmarks. In addition, we also revealed some known and new oncogenic pathways for liver cancer. These included the famous MAPK, TGFβ and cell cycle pathways. New insights were also provided into Wnt signaling, prostate cancer, axon guidance and oocyte meiosis pathways. These signaling and developmental pathways crosstalk to regulate stem cell transformation and implicate a role of miRNAs in hepatic stem cell deregulation and cancer development. By analyzing their complete interactome, we proposed new categorization for some of these miRNAs as either tumor-suppressors or oncomiRs with dual roles. Therefore some of these miRNAs may be addressed as therapeutic targets or used as therapeutic agents. Such dual roles thus expand the view of miRNAs as active maintainers of cellular homeostasis.

Association of vitamin D receptor gene polymorphism(VDR)with vitamin D deficiency,metabolic and inflammatory markers in Egyptian obese women

Vitamin D deficiency might contribute to the pathogenesis of metabolic syndrome and could cause immune disturbance.The aim of this study is to analyze the associations between Vitamin D receptor(VDR)gene polymorphism,serum 25-hydroxy vitamin D,metabolic and inflammatory biomarkers in Egyptian obese women.The study included 201 obese women with vitamin D deficiency and 249 obese matched age healthy controls with sufficient vitamin D levels.Their age ranged between 25 and 35 years.Inflammatory biomarkers(interleukin-6 and C-reactive protein)and serum 25(OH)D were measured by enzyme-linked immunosorbent assay.Insulin resistance(IR)was determined by the homeostasis model assessment of insulin resistance(HOMA-IR).Vitamin D receptor(VDR)gene polymorphisms of FokI,ApaI,and TaqI were studied by PCR using the restriction fragment length polymorphism(RFLP)technique.Obese women with vitamin D deficiency had significant higher values of inflammatory and metabolic parameters compared to controls.Multivariable-logistic regression showed associations between 25(OH)D deficiency and metabolic components when comparing cases with controls.Moreover,cases carrying polymorphic alleles showed significant lower levels of serum 25(OH)D and higher HOMA-IR,blood pressure levels and lipid parameters compared to those with the wild type homozygote in obese cases with vitamin D deficiency.Vitamin D deficiency in Egyptian obese women with vitamin D deficiency is associated with abnormal metabolic components and abnormal inflammatory biomarkers.Moreover,VDR polymorphisms play important role in immune and inflammation status.

Association analysis of FTO gene polymorphisms and obesity risk among Egyptian children and adolescents

Obesity is a common disorder that has a significant impact on human health as it may lead to many serious diseases and sometimes morbidity.Previous genome-wide association studies(GWAS)confirmed that there is a relationship between some variants in the first intron of the fat mass and obesity associated(FTO)gene and obesity in adults and children in different ethnic groups.In our study,the association of the FTO rs9939609 and rs17817449 variants with obesity was investigated in Egyptian children and adolescents.We examined rs9939609 and rs17817449 polymorphisms in 100 control and 100 obese cases,we used the restriction fragment length polymorphism(RFLP)technique to genotype the samples.The current study showed that there were no significant differences(P>0.05)between the cases and controls in both variants of rs17817449 and rs9939609 polymorphisms.However,there were significant correlations between rs17817449 and cholesterol and between rs9939609 and LDL.In Current Study although the two variants(rs9939609 and rs17817449)didn’t show an association with obesity,but there was a correlation between the lipid profile and these two variants.

Immunomodulatory and Antioxidativepotentials of adipose-derived Mesenchymalstem cells isolated from breast versusabdominal tissue: a comparative study

Background: Adipose-derived stem cells (ASCs) are considered ideal candidates for both research and cellular therapydue to ease of access, large yield, feasibility, and efficacy in preclinical and clinical studies. Unlike the subcutaneousabdominal fat depot, breast ASCs features are still not well recognized, limiting their possible therapeutic use. ASCswere found to exert immunomodulatory and antioxidative activities for maintaining homeostasis and functionality ofdiseased/damaged tissues. This study aims to investigate the immunomodulatory and antioxidative potentials of breastversus abdominal isolated ASCs to find out which anatomical site provides ASCs with better immunoregulatory andoxidative stress resistance capabilities.Methods: ASCs were isolated from abdominal and breast tissues. Gene expression analysis was conducted for a panelof immunomodulatory and antioxidative genes, as well as adipokines and proliferation genes. Flow cytometric analysisof a group of immunomodulatory surface proteins was also performed. Finally, the significantly expressed genes haveundergone protein-protein interaction and functional enrichment in silico analyses.Results: Our results revealed similar morphological and phenotypic characteristics for both breast and abdominalASCs. However, a significant elevation in the expression of two potent immunosuppressive genes, IL-10 and IDO aswell as the expression of the multifaceted immunomodulatory adipokine, visfatin, was detected in breast versusabdominal ASCs. Moreover, a significant overexpression of the antioxidative genes, GPX1, SIRT5, and STAT3 and theproliferation marker, Ki67, was also observed in breast ASCs relative to abdominal ones. In silico analysis showed thatboth of the differentially upregulated immunomodulatory and antioxidative mediators integratively involved inmultiple biological processes and pathways indicating their functional association.Conclusion: Breast ASCs possess superior immunomodulatory and antioxidative capabilities over abdominal ASCs. Ourfindings shed light on the possible therapeutic applications of breast ASCs in immune-related and oxidative stressassociateddiseases.