Charcot–Marie–Tooth disease: Genetics, epidemiology and complications

Background and aims: Charcot Marie Tooth disease (CMT) is the most prevalent hereditary neuropathy and its frequency is 1 in 2500. CMT is a heterogeneous disease and has different clinical symptoms. The prevalence of CMT and involved genes differ in different countries. CMT patients experience considerable sleep problems and a higher risk of decreased quality of life. In this work it was aimed to provide a review on the genetic and epidemiologic aspects of this disease. Methods: In the current review article, we performed a literature search on the epidemiology of Charcot–Marie–Tooth disease” and provided a brief review on epidemiology, genetic, and complications of CMT. Databases Web of Science and PubMed were searched using the Endnote software for the publications on CMT during 2000 to 2016. Results: Charcot Marie Tooth disease has different prevalence around the world and is the most common neuropathy. Epidemiological studies have estimated the prevalence of CMT in Japan 1/9200, in Iceland 1/8300, in Spain 1/3500 and in Italy 1/5700.The patients have different phenotype and the age of onset. There is a variety of inherited patterns of disease and many genes have been identified responsible whose mutations are main cause of the disease. Conclusion: Due to the impact of this kind of disabilities on the national health, further studies seem to be necessary to gain better knowledge of the disease particularly in the regions with higher prevalence. Moreover molecular biology services offered by genetic laboratories can reduce the incidence of disorder

Genetics and epidemiology of Middle East Respiratory Syndrome-Coronavirus (MERS-CoV)

Background: Middle East respiratory syndrome (MERS) is a viral respiratory illness caused by a coronavirus. After the primary onset of MERS in Saudi Arabia, in September 2015 cases began to increase. The number of laboratory-affirmed cases by MERS-CoV in the Middle East has been being increased recently. Method: In this current review article, by using the terms “MERS” and “coronavirus” we first searched for English language articles in the PubMed database, published in last five years. Then by a detailed review of related articles, we provided a comprehensive information about epidemiology, genetic, host and coronavirus treatment. Result: More importantly, evidences of human-to-human transmission in Europe and America indicate that the viral adaptations in humans may precede a large-scale epidemic. The genome of Coronaviruses is a linear positive-sense single stranded large RNA and they are enveloped viruses that have a helical symmetric nucleocapsid. Some new insights have been provided in previous few months in to the animal Coronavirus hosts, transmissibility, contagion of MERS Co-V and ideal laboratory diagnostic methods. Conclusion: It seems crucial to control this new human infection “MERS-CoV” by collaborating global and local health authorities and their continual support for further research on it

Integrative computational mRNA-miRNA interaction analyses of the autoimmune-deregulated miRNAs and well-known Th17 differentiation regulators: An attempt to discover new potential miRNAs involved in Th17 differentiation

Th17 cells are a lineage of CD4(+) T helper cells in immune system which differentiate from naive CD4(+) T cells and have demonstrated to play a critical role in the pathogenesis of different autoimmune disorders. miRNAs are a novel group of non-coding RNAs which participate in post-transcriptional regulation of gene expression mostly by pairing with 3'UTR of their mRNA targets and inhibition of its translation. It has been demonstrated that miRNAs function in various cellular processes such as differentiation, proliferation, and apoptosis. By now, several signaling pathways and their downstream positive and negative regulators involve in Th17 differentiation have been discovered. Several studies have reported the aberrant miRNA expression profile in patients with autoimmune disease called autoimmune-deregulated miRNAs. Here, using integrative miRwalk database which assembles the data gathered from ten different bioinformatics databases designed to predict miRNA-target interaction, we analyzed possible targeting effect of ``autoimmune-deregulated miRNAs'' on prominent positive and negative regulators of Th17 differentiation. Our resulting mRNA-miRNA network simply nominated several miRNAs with strong possibility which probably may have inducing (miR-27b, miR-27a, miR-30c, miR-1, and miR-141) or inhibitory (miR-20b, miR-93, miR-20a, miR-152, miR-21, and miR-106a) role in Th17 differentiation by targeting negative or positive regulators of Th17 differentiation, respectively. (C) 2015 Elsevier B.V. All rights reserved

MiR-218 as a multifunctional regulator of oncogenic processes in different solid tumors

MicroRNAs are highly conserved small non-coding regulatory RNAs that involve in post transcriptional regulating of gene expression during different cellular mechanisms. Aberration of miR-218 expression during tumorigenesis of different solid tumors has been reported by numerous studies. In current systematic review article, by using the terms “miR-218” and “cancer” we first searched for English language articles in the PubMed database, published from 1993 to April 2014. Then by a comprehensive review of related articles, we provided some new insights that highlight novel features and functions of miR-218 in initiation and progression of solid tumors. The majority of these studies propose a tumor suppressing role for miR-218 considering the fact that it is significantly down-regulated in tumor tissues compared with normal specimens. Despite accumulating body of evidence regarding tumor suppressor functions of miR-218 in solid tumors; more intensive reviewing about available miR-218 recent original studies and interpretation of existing data, revealed the multifunctional role of miR-218 in these kinds of malignancies by targeting different corresponding target genes. Take all together, MiR-218 targets different cellular processes in cancer cells and its expression pattern is in an important association with various states and features of tumors. It seems that miR-218 can increase the speed of cell cycle and cell division in lower sample grades and along with progression of cancer cells it's function changes to stabilization the cancer cells and not allowing them to invade. thats why it often shows up-regulation in lower grades and down-regulation in metastatic phase. Therefore, it seems of great importance to check samples stage, grade, lymph node metastasis status and other tumor features before evaluation of miR-218 as a prognostic or diagnostic biomarker. © 2016, Iranian Neurogenetics Society. All rights reserved

Molecular Mechanisms behind Free Radical Scavengers Function against Oxidative Stress

Accumulating evidence shows that oxidative stress is involved in a wide variety of human diseases: rheumatoid arthritis, Alzheimer’s disease, Parkinson’s disease, cancers, etc. Here, we discuss the significance of oxidative conditions in different disease, with the focus on neurodegenerative disease including Parkinson’s disease, which is mainly caused by oxidative stress. Reactive oxygen and nitrogen species (ROS and RNS, respectively), collectively known as RONS, are produced by cellular enzymes such as myeloperoxidase, NADPH-oxidase (nicotinamide adenine dinucleotide phosphate-oxidase) and nitric oxide synthase (NOS). Natural antioxidant systems are categorized into enzymatic and non-enzymatic antioxidant groups. The former includes a number of enzymes such as catalase and glutathione peroxidase, while the latter contains a number of antioxidants acquired from dietary sources including vitamin C, carotenoids, flavonoids and polyphenols. There are also scavengers used for therapeutic purposes, such as 3,4-dihydroxyphenylalanine (L-DOPA) used routinely in the treatment of Parkinson’s disease (not as a free radical scavenger), and 3-methyl-1-phenyl-2-pyrazolin-5-one (Edaravone) that acts as a free radical detoxifier frequently used in acute ischemic stroke. The cell surviving properties of L-DOPA and Edaravone against oxidative stress conditions rely on the alteration of a number of stress proteins such as Annexin A1, Peroxiredoxin-6 and PARK7/DJ-1 (Parkinson disease protein 7, also known as Protein deglycase DJ-1). Although they share the targets in reversing the cytotoxic effects of H2O2, they seem to have distinct mechanism of function. Exposure to L-DOPA may result in hypoxia condition and further induction of ORP150 (150-kDa oxygen-regulated protein) with its concomitant cytoprotective effects but Edaravone seems to protect cells via direct induction of Peroxiredoxin-2 and inhibition of apoptosis

Hearing loss: A review on molecular genetics and epidemiologic aspects

Background and aims: Hearing loss (HL) happens due to the genetic or environmental causes or both. Risk factors include congenital infections and congenital deformities of auricle and ear duct. The present study was performed to briefly explain the genetics, molecular biology and epidemiology of HL in Middle East especially in Iran. Methods: An intense an comprehensive literature search was prformed through heading journals in the field. All data was organized using Mendeley software and incorporated to the text as required. Results: While the etiology of 25 of HL cases remains indistinct, it is estimated that at least 50 of pre lingual HL cases have a genetic cause. About 70 of genetic HL cases are non Syndromic (NSHL) without anomaly, whereas the remaining 30 are Syndromic. Autosomal recessive non-syndromic hearing loss forms (ARNSHL) are the severest forms of congenital HL with defect in cochlea. In addition to X-linked (DFNX), autosomal dominant (DFNA), autosomal recessive (DFNB) and Y-linked (DFNY) inheritance patterns, HL can be inherited through mitochondrial genes including MT-RNR1 and MT-TS. At least 120 genes have been reported to be associated with HL. Among them, mutations in connexin 26 (GJB2) have been shown to play a very important role in developing ARSNSHL in many populations depending on geographical location and ethnicity. In Caucasians and Spainish/Italian populations, 50 and 79 of HL cases have respectively been reported to be occurred due to mutations in GJB2 gene. Conclusion: In the Middle East, the prevalence seems different as an average of 14-20 of the HL in several region of Iran is due to mutation in GJB2 gene. Alternatively similar studies showed the prevalence of GJB2 mutations around 25 and 6.1 in Turkey and Pakistani populations respectively

MicroRNAs: effective elements in ear-related diseases and hearing loss

miRNAs are important factors for post-transcriptional process that controls gene expression at mRNA level. Various biological processes, including growth and differentiation, are regulated by miRNAs. miRNAs have been demonstrated to play an essential role in development and progression of hearing loss. Nowadays, miRNAs are known as critical factors involved in different physiological, biological, and pathological processes, such as gene expression, progressive sensorineural hearing loss, age-related hearing loss, noise-induced hearing loss, cholesteatoma, schwannomas, and inner ear inflammation. The miR-183 family (miR-183, miR-96 and miR-182) is expressed abundantly in some types of sensory cells in inner ear specially mechanosensory hair cells that exhibit a great expression level of this family. The plasma levels of miR-24-3p, miR-16-5p, miR-185-5p, and miR-451a were upregulated during noise exposures, and increased levels of miR-21 have been found in vestibular schwannomas and human cholesteatoma. In addition, upregulation of pro-apoptotic miRNAs and downregulation of miRNAs which promote differentiation and proliferation in age-related degeneration of the organ of Corti may potentially serve as a helpful biomarker for the early detection of age-related hearing loss. This knowledge represents miRNAs as promising diagnostic and therapeutic tools in the near futur

Lower expression of miR-218 in human breast cancer is associated with lymph node metastases, higher grades, and poorer prognosis.

Breast cancer is considered as the most prevalent malignancy in women worldwide. Despite emergence of several prognosticators for better management of patients, there are still limitations for their clinical application due to the complexity of breast tumors, and therefore, new biomarkers for better prognosis of clinical outcomes would be of the great essence. MicroRNAs are highly conserved small non-coding regulatory RNAs involved in post-transcriptional regulating of gene expression during different cellular mechanisms. Accumulating studies suggest that miR-218 plays a multifunctional role in various cancer types and different stages. Here, to address prognostic significance of miR-218 in breast cancer, we investigate the expression profile of miR-218 and B-cell-specific Moloney murine leukemia virus integration site 1 ( BMI1) gene, as one of the putative targets of miR-218, in 33 paired breast tumors and their adjacent normal tissues with respect to the clinicopathological features of patients using quantitative real-time polymerase chain reaction. The correlation of both miR-218 and BMI1 gene expression with overall survival of breast cancer patients was also examined recruiting OncoLNC data portal. Finally, to better understand biological function of miR-218 in breast cancer, we performed in silico Gene Ontology and signaling pathway enrichment analysis on miR-218 targetome. According to our data, significant elevation of the expression of miR-218 and downregulation of BMI1 were observed in clinical breast cancer specimens compared with normal tissues ( p < 0.0001). The lower expression of miR-218 was associated with lymph node metastases, higher grades, and poorer prognosis (logrank p = 0.00988), whereas no significant difference in overall survival was observed between patients with higher and lower expression of BMI1 (logrank p = 0.254). These findings suggest that miR-218 expression profiling might be clinically applicable as a prognostic biomarker in breast cancer. In addition, our in silico enrichment analyses revealed that the association of miR-218 expression with breast cancer prognosis might be through its involvement in endocytosis and gap junction biological pathways

Comparative evaluation of the effects of three hydraulic calcium silicate cements on odontoblastic differentiation of human dental pulp stem cells: an in vitro study

Objective: The study aimed to compare the response of human dental pulp stem cells (hDPSCs) towards three hydraulic calcium silicate cements (HCSCs) by measuring cytotoxicity and expression of dentinogenic genes. Methodology: Dental pulps of five impacted mandibular third molars were extirpated as a source for hDPSCs. Next to culturing, hDPSCs were subjected to fluorescence-activated cell sorting after the third passage to validate stemness of the cells. Human DPSCs were exposed to diluted supernatants of OrthoMTA (OMTA), Biodentine (BD) and Calcium-Enriched Mixture (CEM) at concentrations 10, 25, 50 and 100% at the first, third and fifth day of culture. Then, cells were exposed to 10% concentrations supernatant of HCSCs to determine DSPP and DMP1 gene expression, using a quantitative polymerase-chain reaction. Data were analyzed using one-way and three-way ANOVA, followed by Tukey post hoc statistical tests. Results: Optimal cell proliferation was observed in all groups, regardless of concentration and time-point. HCSC supernatants were non-cytotoxic to hDPSCs at all three time-points, except for 100% Biodentine on day five. On day seven, OMTA group significantly upregulated the expression of DSPP and DMP1 genes. On day 14, expression of DMP1 and DSPP genes were significantly higher in BD and OMTA groups, respectively. Conclusion: Biodentine significantly upregulated DMP1 gene expression over 14 days, whereas CEM was associated with only minimal expression of DSPP and DMP1 . &nbsp

Edaravone leads to proteome changes indicative of neuronal cell protection in response to oxidative stress

Neuronal cell death, in neurodegenerative disorders, is mediated through a spectrum of biological processes. Excessive amounts of free radicals, such as reactive oxygen species (ROS), has detrimental effects on neurons leading to cell damage via peroxidation of unsaturated fatty acids in the cell membrane. Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) has been used for neurological recovery in several countries, including Japan and China, and it has been suggested that Edaravone may have cytoprotective effects in neurodegeneration. Edaravone protects nerve cells in the brain by reducing ROS and inhibiting apoptosis. To gain further insight into the cytoprotective effects of Edaravone against oxidative stress condition we have performed comparative two-dimensional gel electrophoresis (2DE)-based proteomic analyses on SH-SY5Y neuroblastoma cells exposed to oxidative stress and in combination with Edaravone. We showed that Edaravone can reverse the cytotoxic effects of H2O2 through its specific mechanism. We observed that oxidative stress changes metabolic pathways and cytoslceletal integrity. Edaravone seems to reverse the H2O2-mediated effects at both the cellular and protein level via induction of Peroxiredoxin-2. (C) 2015 Elsevier Ltd. All rights reserved