第4卷，第2期

1178

With rapid advances in understanding molecular pathogenesis of human diseases in the era of genome sciences and systems biology, it is anticipated that increasing numbers of therapeutic genes or targets will become available for targeted therapies. Despite numerous setbacks, efficacious gene and/or cell-based therapies still hold the great promise to revolutionize the clinical management of human diseases. It is wildly recognized that poor gene delivery is the limiting factor for most in vivo gene therapies. There has been a long-lasting interest in using viral vectors, especially adenoviral vectors, to deliver therapeutic genes for the past two decades. Among all currently available viral vectors, adenovirus is the most ef ficient gene delivery system in a broad range of cell and tissue types. The applications of adenoviral vectors in gene delivery have greatly increased in number and efficiency since their initial development. In fact, among over 2000 gene therapy clinical trials approved worldwide since 1989, a significant portion of the trials have utilized adenoviral vectors. This review aims to provide a comprehensive overview on the characteristics of adenoviral vectors, including adenoviral biology, approaches to engineering adenoviral vectors, and their applications in clinical and preclinical studies with an emphasis in the areas of cancer treatment, vaccination and regenerative medicine. Current challenges and future directions regarding the use of adenoviral vectors are also discussed. It is expected that the continued improvements in adenoviral vectors should provide great opportunities for cell and gene therapies to live up to its enormous potential in personalized medicine.

1227

The recent and exciting discovery of germline HOXB13 mutations in familial prostate cancer has brought HOX signaling to the forefront of prostate cancer research. An enhanced understanding of HOX signaling, and the co-factors regulating HOX protein specificity and transcriptional regulation, has the high potential to elucidate novel approaches to prevent, diagnose, stage, and treat prostate cancer. Toward our understanding of HOX biology in prostate development and prostate cancer, basic research in developmental model systems as well as other tumor sites provides a mechanistic framework to inform future studies in prostate biology. Here we describe our current understanding of HOX signaling in genitourinary development and cancer, current clinical data of HOXB13 mutations in multiple cancers including prostate cancer, and the role of HOX protein co-factors in development and cancer. These data highlight numerous gaps in our understanding of HOX function in the prostate, and present numerous potentially impactful mechanistic and clinical opportunities for future investigation.

1200

The recent emerging field of regenerative medicine is to present solutions for chronic diseases which cannot be sufficiently repaired by the body's own mechanisms. Stem cells are undifferentiated biological cells and have the potential to develop into many different cell types in the body during early life and growth. Self renewal and totipotency are the characteristic features of stem cells and it holds a promising result for treating various diseases like diabetic foot ulcer, heart diseases, lung diseases, Autism, Skin diseases, arthritis including eye disease. Failure of complete recovery of eye diseases and complications that follow conventional treatments have shifted search to a new form of regenerative medicine using Stem cells. The ocular progenitor cells are remarkable in stem cell biology and replenishing degenerated cells despite being present in low quantity and quiescence in our body has a high therapeutic value. In this paper we have review the applications on ocular progenitor stem cells in treatment of human eye diseases and address the strategies that have been exploited in an effort to regain visual function in the advance treatment of stem cells without any side effects and also present the significance in advance stem cell research.

1254

The majority of cancer-related deaths are caused by tumor recurrence, metastasis and therapeutic resistance. During the late stages of tumor progression, multiple factors are involved, including the downregulation and/or loss of function of metastasis suppressors. Epithelial protein lost in neoplasm (EPLIN), an actin-binding protein, was initially identified as a putative tumor suppressor that is frequently downregulated in epithelial tumors. Recent evidence indicates that EPLIN may negatively regulate epithelia-to-mesenchymal transition (EMT), a crucial process by which cancer cells acquire invasive capabilities and therapeutic resistance. Importantly, downregulation of EPLIN is associated with clinical metastasis in a variety of solid tumors, suggesting that EPLIN could be a suppressor of metastasis. In this review, I will discuss the regulation and function of EPLIN in human cancer cells and explore the clinical significance of EPLIN in metastatic disease.

1306

Allergic asthma is a diverse chronic respiratory disease characterized by the inflammation of the lower airway disease affecting many people around the world with rising morbidity and mortality. Association between asthma and certain demographic features was studied in relation to genotype from 244 allergic individuals of local population. Skin prick test was used to confirm asthma. Genetic polymorphism in Glutathione-S-transferases (GSTs) was studied using multiplex PCR based method and IgE level by ELISA. Pollen and dust were the major causative aeroallergens (26%), which were associated to higher IgE levels (P < 0.05). Smoking was found to be significantly associated with asthma in only males (P = 0.004). A low prevalence of null genotype of both GSTM1 and GSTT1 genes was observed in the patients (4.34%) compared to control group (14%). No association of combined GSTM1 and GSTT1 null genotype was found with the asthma in local population. GSTM1+ and GSTT- genotype had higher risk (OR = 1.3681, P = 0.001) for development of asthma. There was a significant association of asthma with combined genotype of GSTM1+ and GSTT- when data was analyzed on gender basis in males (P = 0.006) and highly significant in age range of 26-40 years (P = 0.001). Combined GSTM⁺ and GSTT^- genotype was found to be risk factor for asthma in addition to family history in male patients. However a data with large patient size and different ethnic distribution may reveal the exact etiology.

1258

The purpose of this study is to measure the expression of microRNA-4463 and microRNA-6087 between normal persons and patients with hepatocellular carcinoma (HCC), and to clarify the meaning of them in the prognosis evaluation in HCC. Forty-five samples from healthy people and patients, who had been diagnosed with hepatocellular carcinoma before any treatment, were collected to study respectively. Real-time PCR was used to detect the expression of miRNA-4463 and miRNA-6087 in the serum of control group and hepatocellular carcinoma patients. The expression of miR-4463 in the serum of HCC patients was significantly higher than that in control group (P < 0.05), and the expression level was independent of gender, tumor size, cell types, stages, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL) and HBsAg status (P > 0.05). But there was a significant difference of different level of AFP in HCC (P < 0.05), and the difference between the group of AFP lower than 400 ug/l and the control group is statistically significant (P < 0.05). Besides, the survival time had showed a significant difference at the high and low expression levels (P < 0.05). But the expression level of miRNA-6087 was no difference in HCC and control group. The disorder of miRNA-4463 occurred in HCC, even the AFP level doesn't rises. What's more, patients who get the high level of miRNA-4463 seem to have a shorter survival time. And it contributes great to the prognostic evaluation. This is the first study to illustrate the potential significance of miRNA-4463 in the prognosis in HCC.

1285

In the present study we attempted a parent-child trio, whole exome sequencing (WES) approach to study Apert's syndrome. Clinical characteristics of the child were noted down and WES was carried out using Ion Torrent System that revealed the presence of previously reported P253R mutation in FGFR2 gene. Presence of two SNPs rs1047057 and rs554851880 in FGFR2 gene with an allelic frequency of 0.5113 and 0.001176 respectively and 161 complete damaging mutations were found. This study is the first reported case of exome sequencing approach on an Apert's syndrome patient aimed at providing better genetic counselling in a non-consanguineous relationship.

1227

Insulin signal is one of the vital signaling cascade required for Schwann cells to myelinate the axons of peripheral nervous system (PNS). Myelin formation of peripheral nerve is a complex molecular event controlled by different neurotrophic and transcription factors. The altered or failure in this signaling progression is one of the reasons behind the demyelination of peripheral neurons in diabetic peripheral neuropathy (DPN). The Schwann cell in PNS includes POU domain transcription factor OCT-6 expression. This factor is considered as crucial for the initiation and enhancement of myelination during nerve regeneration. To know the importance of OCT-6 gene, here we studied the long term expression of OCT-6 nuclear protein in sciatic nerve of normal and diabetic neuropathic rats. Also for the first time we elucidated the role of insulin in controlling the expression of OCT-6 in hyperglycemic Schwann cells and sciatic nerve of diabetic neuropathic rats. The results shows that, there will be long term OCT-6 expression in sciatic nerve of adult rats and also their significant decrease is observed in the diabetic condition. But, addition of Insulin for primary Schwann cells and diabetic rats shows the increased OCT-6 expression in both in vivo and in vitro. Together these results indicate the failure of OCT-6 support in neuropathy and also the importance of insulin signaling cascade in the expression of OCT-6 transcription factor.

1243

Obesity is complex heterogeneous disease controlled by genes, environmental factors, and their interaction. Genetic factors account for 40—90% of the body mass index variations. Body mass index (BMI) of children correlates more closely with maternal than paternal BMI. So, this studu was aimed to investigate the role of leptin receptor LEPR Gln223Arg, the uncoupling protein 2 (UCP2 G 866 A) and insulin receptor gene (INSR exon 17) polymorphisms in the pathogenesis of obesity. A cross-sectional study executed on 130 children and their obese mothers; classified into 2 groups according to their BMI. The 2 groups were evaluated regarding the anthropometry. Restriction fragment length analysis for LEPR Gln223Arg, UCP2-866 G/A and INSR exon 17 polymorphisms were applied. It was reported that increased risk of obesity was found in LEPR AG + AA genotype and the A allele. Significant statistical difference was detected only in female children. Concerning UCP2, the AG followed by the GG genotype was the most frequent in all groups and the G allele was the mostly present in obese mothers and obese male children but with no statistical significance. There was difference in the INSR genotype and alleles between groups, but this difference was not statistically significant. This study concluded that the LEPR Gln223Arg, UCP2 G 866 A and INSR exon 17 polymorphisms are related to obesity in Egyptian population. Further researches on larger population are recommended to ascertain the implications of LEPR, UCP2 and INSR polymorphisms in obesity.

1218

Our previous studies have demonstrated that proline-rich protein 11 (PRR11) is a novel tumor-related gene and implicates in regulating the proliferation in lung cancer. However, its precise role in cell cycle progression remains unclear. Our recent evidences show that PRR11 silencing has an effect on autophagy in non-small-cell lung cancer (NSCLC) cells. Two human NSCLC cell lines, H1299 and A549 were transiently transfected with against PRR11 siRNA. The Cell Counting Kit-8 and plate clone formation assay showed that downregulation of PRR11 inhibited the cell proliferation associated with cell cycle related genes reduced. And our data suggested that PRR11 depletion expression enhanced the autophagosomes formation, followed with downregulation of P62 and upregulation of LC3-II protein. Furthermore, the immunoblotting results indicated that silencing of PRR11 inactivated the Akt/mTOR signaling pathway. Collectively, these results demonstrated PRR11 had an effective role in autophagy in NSCLC cells through Akt/mTOR autophagy signaling pathways. Therefore, it is helpful to clarify the function of PRR11 in tumorigenesis of NSCLC.

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