Evaluation of altered expression of miR-9 and miR-106a as an early diagnostic approach in gastric cancer.

BACKGROUND: The role of microRNAs (miRNAs) in cellular processes such as growth, apoptosis, differentiation and proliferation verifies the importance of miRNAs in carcinogenesis. Moreover, levels of miRNAs are dysregulated in cancer cells, so they could be used as novel classes of biomarkers for diagnosing cancer. The oncogenic role of miR-106a and its increased expression have been demonstrated in some cancers. In contrast, there is no consensus for miR-9 expression rate in different cancers. Therefore, this study was done to investigate the role of miR-106a and miR-9 in gastric cancer (GC). METHODS: The current study was performed on 31 GC tissues as case, and 31 healthy adjacent tissues as a control group. Quantitative reverse transcriptase (q-RT) PCR was used for studying the expression rate of both miR-106a and miR-9. RESULTS: The expression rate of both miRNAs in cancerous tissues was significantly higher than healthy adjacent tissues (≈10 folds) (P<0.05). CONCLUSIONS: The results showed that the expression rate of both markers was significantly increased in cancerous tissues. Therefore, they can be suggested as potential biomarkers for cancer diagnosis and prognosis as well as targets for therapy.

Efflux proteins at the blood-brain barrier: review and bioinformatics analysis.

1. Efflux proteins at the blood-brain barrier provide a mechanism for export of waste products of normal metabolism from the brain and help to maintain brain homeostasis. They also prevent entry into the brain of a wide range of potentially harmful compounds such as drugs and xenobiotics. 2. Conversely, efflux proteins also hinder delivery of therapeutic drugs to the brain and central nervous system used to treat brain tumours and neurological disorders. For bypassing efflux proteins, a comprehensive understanding of their structures, functions and molecular mechanisms is necessary, along with new strategies and technologies for delivery of drugs across the blood-brain barrier. 3. We review efflux proteins at the blood-brain barrier, classified as either ATP-binding cassette (ABC) transporters (P-gp, BCRP, MRPs) or solute carrier (SLC) transporters (OATP1A2, OATP1A4, OATP1C1, OATP2B1, OAT3, EAATs, PMAT/hENT4 and MATE1). 4. This includes information about substrate and inhibitor specificity, structural organisation and mechanism, membrane localisation, regulation of expression and activity, effects of diseases and conditions and the principal technique used for in vivo analysis of efflux protein activity: positron emission tomography (PET). 5. We also performed analyses of evolutionary relationships, membrane topologies and amino acid compositions of the proteins, and linked these to structure and function.

Evaluation of miR-22 and miR-20a as diagnostic biomarkers for gastric cancer.

BACKGROUND: Gastric cancer (GC) is the fourth most common cancers and the second reason for cancer-related death around the world, particularly in East Asian countries. Diagnosing GC in its early stages is followed by more successful treatment. Unfortunately, there is no accurate method for GC diagnosis in its early stages. Recently, miRNAs have been investigated in the most cancer researches which have demonstrated that they have been dysregulated in many cancers. METHODS: This case-control study aims to investigate the expression rate of miR-22 and miR-20a in 32 cancerous tissues as well as 32 healthy adjacent tissues. Quantitative reverse transcriptase PCR (q-RT PCR) was used for investigating the expression rate of these miRNAs. RESULTS: The expression rate of miR-20a in cancerous tissues was significantly increased (8.9 times) in comparison with their healthy tissues (P<0.001), while the expression rate of miR-22 in cancerous tissues was significantly decreased (1.9 times) (P<0.05). CONCLUSIONS: The obtained results suggest miR-22 and miR-20a as good diagnostic biomarkers for early detection of GC. However more research is needed to investigate their efficacy.

Prolyl hydroxylase inhibitors act as agents to enhance the efficiency of cell therapy.

INTRODUCTION: In stem cell-based therapy as a subtype of regenerative medicine, stem cells can be used to replace or repair injured tissue and cells in order to treat disease. Stem cells have the ability to integrate into injured areas and produce new cells via processes of proliferation and differentiation. Several studies have demonstrated that hypoxia increases self-renewal, proliferation and post-homing differentiation of stem cells through the regulation of hypoxia-inducible factor-1 (HIF-1)-mediated gene expression. Thus, pharmacological interventions including prolyl hydroxylase (PHD) inhibitors are considered as promising solutions for stem cell-based therapy. PHD inhibitors stabilize the HIF-1 and activate its pathway through preventing proteasomal degradation of HIF-1. AREAS COVERED: This review focuses on the role of hypoxia, HIF-1 and especially PHD inhibitors on cell therapy. PHD structure and function are discussed as well as their inhibitors. In addition, we have investigated several preclinical studies in which PHD inhibitors improved the efficiency of cell-based therapies. EXPERT OPINION: The data reviewed here suggest that PHD inhibitors are effective operators in improving stem cell therapy. However, because of some limitations, these compounds should be properly examined before clinical application.