The role of microRNAs in the pathogenesis, diagnosis and treatment of prostate cancer

Prostate cancer is one of the major health problems and the second cause of cancer mortality in men over 40 years age in developed countries. Due to the incomplete screening methods for sensivity and spesificity detection prostate cancer, alternative methods with more specificity than are desired. With recent advances in molecular technology, numerous biomarkers have been suggested for the screening of prostate cancer with greater accuracy. MicroRNAs are oligonucleotides with 18-24 length that have key roles in post-transcriptional regulation of gene expression as well as other cellular process (apoptosis, cell proliferation, differentiation and angiogenesis). Many studies have demonstrated changing of the expression levels of microRNAs in prostate cancer patients. Therefore, they can be implemented for the development of prognostic or diagnostic biomarkers. Owing to microRNAs can target molecular signaling pathways and genes involved in prostate cancer, they may also be applicable for therapeutic purposes. In this review article, we explain the roles of microRNAs in different cancer pathways and specifically the pathogenesis, diagnosis and treatment of prostate cancer. Keywords: Prostate Cancer, MicroRNAs, Biomarker

The current applications of cell-free fetal DNA in prenatal diagnosis of single-gene diseases: A review

Prenatal diagnosis of hereditary diseases has substantially altered the way medical geneticists are helping families affected by genetic disorders. However, the risk of miscarriage and fear of invasive diagnostic procedures may discourage many couples from seeking prenatal diagnosis. With the discovery of maternal plasma cell-free fetal DNA, prenatal diagnosis has entered a new era of progress. Cell-free DNA is released during normal physiological functions as well as through the cell death programs of apoptosis and necrosis. It can be found in the plasma and other body fluids. Although this method has the advantage of being noninvasive, it is still rather expensive and requires advanced hardware and comprehensive data analysis. Promising implications of noninvasive prenatal diagnosis methods for the diagnosis of common trisomy disorders have paved the way for the development of more complicated assays of single-gene disorders. Relative mutation dosage and relative haplotype dosage are the most widely implemented assays for noninvasive prenatal diagnosis of single-gene disorders. However, each assay has its own advantages and disadvantages. Relative mutation dosage is based on the droplet digital polymerase chain reaction (PCR) technique which includes quantification features of real-time PCR assays. Relative haplotype dosage is based on next-generation sequencing that includes analysis of the maternal and paternal genome followed by sequencing of maternal plasma cell-free DNA. Co-amplification at a lower denaturation temperature PCR is another approach that is based on forming heteroduplexes between alleles to selectively amplify paternal mutations. In this review, we have described the most common noninvasive prenatal diagnosis approaches and compared their applications in genetic disorder diagnosis with different inheritance patterns. Key words: Cell-free nucleic acids, Prenatal diagnosis, Noninvasive prenatal testing, Single-gene diseases, Non-invasive techniques

Distribution of Disease-Causing Mutations through Different Protein Domains in Patients with Severe Combined Immunodeficiency

Background and Aim: Severe combined immunodeficiency (SCID) has been described as the most severe form of primary immunodeficiency disorders (PID). The disease can be caused by mutations in more than 20 different genes with prevalence of 1 in 50000 to 100000 live births. In the present study, we described the protein domain position of variants in 14 main genes in patients with SCID. We also aimed to investigate the correlation between the variant distribution of protein domains and its pathogenicity and clinical outcome of the variant. Materials and Methods: Molecular genetic analysis including Sanger sequencing, targeted gene panel and whole exome sequencing were performed on 50 patients with SCID. Moreover, protein domains characteristics were extracted from different databases such as Uniprot and PDB and the reported mutations were obtained from HGMD and ENSEMBL databases. Results: Our results showed that the mortality rate had a significant correlation with severity of clinical manifestations in the patients (p-value=0.000). There was also a significant relationship between the protein type and mutation severity (p-value=0.001) and severity of clinical manifestations (p-value=0.025). However, there was no significant relationship between the mortality rate and occurrence of mutations in different domains of proteins (p-value=0.304) and the severity of mutations (p-value= 0.586). Conclusion: In severe genetic diseases such as SCID, mutations in related genes have affected the structure of the protein enough to cause severe symptoms. However, there are differences in the pathogenicity of the mutations based on their location on the protein domains. In order to determine these variations and predict the outcome of mutations, it is necessary to use in silico and laboratory methods along with statistical and data mining tools to track these minor differences

Evaluation of the changes in the expression levels of miR-141 and SHP gene in prostate cancer specimens

Introduction: Primary screening tests currently used for prostate cancer (PCa), don’t have sufficient sensitivity and specificity. Therefore, early diagnosis and management of treatment is one of the challenges faced by physicians. Today, more familiar with the signaling pathways involved in the pathogenesis of cancers, several molecules have been introduced as diagnostic biomarker or drug design. The androgen receptor is one of the most important pathways involved in the pathogenesis of PCa. The miR-141, as a member of the miR-200 family has a regulatory role by targeting the Small heterodimer partner (SHP , NR0B2) at the downstream of this molecular pathway. Objective: The aim of this study was to investigate changes in the expression of miR-141 and SHP in tissue samples of PCa patients compared to benign prosttic hyperplasia (BPH) tissues. Method: In this study, changes in expression of miR-141 and SHP at the RNA level were performed using qRT-PCR technique on 68 prostate tissues containing, 26 localized PCa, 4 metastatic PCa, 30 BPH and 8 tumor-adjacent normal tissues. Also, the analysis of the results was investigated using REST software. Changes in SHP expression at protein level were investigated in 20 Paraffin-embedded tissue blocks containing 10 PCa and 10 BPH using immunohistochemistry (IHC). Results: The findings of this study showed that miR-141 increased in metastatic samples compared with localized samples (P <0.001, 31.17-fold change). Tumor samples showed a lower expression level of SHP compared with BPH tissues at mRNA and protein level (p = 0.014, 4.7 fold change) and (p = 0.02, 1.8 fold change), respectively. Conclusion: According to our results, it can be concluded that miR-141 plays a role in the pathogenesis of PCa through the androgen receptor signaling pathway and the SHP regulation. Also, miR-141 has a high potential for diagnosis of PCa as a prognostic biomarker. Keywords: Prostate cancer, SHP gene, miR-141, Biomarke

Effects of Endurance and Resistance Training on Calcitonin Gene-Related Peptide and Acetylcholine Receptor at Slow and Fast Twitch Skeletal Muscles and Sciatic Nerve in Male Wistar Rats

The aim of this study was to investigate effects of endurance and resistance training (ET and RT) on CGRP and AChRs at slow and fast twitch muscles and sciatic nerve in rats. Twenty-five male rats were randomly assigned into three groups including sedentary (SED), endurance training (ET), and resistance training (RT). Animals of ET exercised for 12 weeks, five times/week, and 60 min/day at 30 m/min. Animals of RT were housed in metal cage with 2 m high wire-mesh tower, with water bottles set at the top. 48 h after the last session of training protocol, animals were anaesthetized. The right sciatic nerves were removed; then, Soleus (SOL) and Tibialis anterior (TA) muscles were excised and immediately snap frozen in liquid nitrogen. All frozen tissues were stored at −80°C. Results showed that, after both ET and RT, CGRP content as well as AChR content of SOL and TA muscles significantly increased. But there was no significant difference among groups at sciatic nerve' CGRP content. In conclusion, data demonstrate that ET and RT lead to changes of CGRP and AChR content of ST and FT muscles. The changes indicate to the importance of neuromuscular activity

Essential Thrombocytosis Following Multiple Psychic Traumas

The associations between exposure to traumatic events and psychiatric disorders such as posttraumatic stress disorder (PTSD), depression, and anxiety have been established. It is important that clinicians notice to this phenomenon and avoid from inappropriate interpretations and additional laboratory tests. Here, a case of 45-year-old man with Essential thrombocytosis developed after multiple psychic traumas was introduced

Life expectancy at birth in Aran-Bidgol region, Iran, 2012: A study based on corrected Health Houses data

Background and aims: Life expectancy is one of the most important indicators of health and well-being of a society. Since it is claimed that in Aran-Bidgol region, center of Iran, life expectancy is higher than the average of the country, this study was designed. Methods: During a cross-sectional study, population and mortality data of Kashan University of Medical Sciences (KAUMS) in 2011 were used for calculating life expectancy. Brass Growth-Balance method was used to adjustmortality data with over 5 years old and to correct under reporting of deaths. Completeness and coverage of death registration data and the correction factor were calculated. Finally, anadjustedlife table for males and females was calculated separately. Microsoft Excel 2007 was used for calculations. Results: Population of Aran-Bidgol was 93571 in 2012 based on KAUMS data. Among the total population, 47331 (50.6) were males. Number of registered deaths was 479 280 male (58.4%). Completeness of the death registration data was found to be %74.9 for males and %70.1 for females. Correction factor (K) for adjustment of reported death was calculated to be 1.33 and 1.42 for males and females respectively. Adjusted life expectancy at birth for males and females was 71.3 and 76.5 years respectively. Conclusion:Although adjusted life expectancy for females in our study was to some extent more than the average life expectancy of Iranian women, but this indicator was slightly lower in men. Generally, it seems that there is no considerable difference between life expectancy of Aran-Bidgol population and national average life expectancy

The effect of MDMA and pentoxifylline drug on bad/bcl-xl gene dosage expression changes on rat liver

        MDMA generally known as ecstasy, have deleterious effects on the serotonergic neurotransmitter system. Recent findings suggest that the liver and brain are major target organs of MDMA-related toxicities. Although most research is being dynamically performed on brain, however, the molecular mechanisms by which MDMA elicits adverse effects in both organs are poorly undrestood.The present study was performed to obtain evidence for molecular mechanism of apoptosis involved in MDMA-induced hepatotoxicity in rat liver after MDMAadministration. Moreover, the antagonistic effect of pentoxifylline was assessed on hepatotoxicity after MDMA administration. In this experimental study, sample size and power in each group were calculated as 10 rats with 95% confidence level and 5% confidence interval. In the study, four experimental groups were selected including Control Normal, MDMA, MDMA+PTX and PTX+MDMA. MDMA was dissolved in PBS and intraperitoneally injected three doses of 7.5mg/kg with two hours gap between doses. Pentoxyfilline also was injected as 100mg/kg, simultaneously with third dose of MDMA. After treatment, total RNA was isolated from liver tissue (5mg). Absorbance at 260nm, 280nm and 230nm were measured and immediately reverse transcription was performed. Included target genes were BAD and BCL-XL as pro-apoptotic and anti-apoptotic gene, respectively. After set up and validation, Real-Time PCR were performed and obtaining data were statistically analyzed to determine significantly differences between groups. Using Real-Time quantitative PCR results, BCL-XL gene expression ratio significantly increased in MDMA+PTX group. Moreover, BAD gene expression ratio increased and up-regulated in PTX+MDMA group (P-value &lt;0.001).Our study focused on molecular mechanism of MDMA in programmed cell death using gene expression quantification of a pro-apoptotic and anti-apoptoic gene in MDMA-induced hepatotoxocity. The results shown MDMA prompted apoptosis in liver and pentoxifylline protects hepatotoxicity after and befor taking MDMA.

Developmental periods of Oenopia conglobata contaminata (Col.: Coccinellidae) reared on eggs of Sitotroga cerealella (Lep.: Gelechiidae) and Ephestia kuehniella (Lep.: Pyralidae) at constant temperatures

The coccinellid Oenopia conglobata contaminata (Menteries) is one of the most important predators of orchard pests in Iran. The effect of eggs of Sitotroga cereallela Olivier (Lep.: Gelechiidae) and Ephestia kuehniella Zeller (Lep.: Pyralidae) on development and survival of this beetle was studied and compared under laboratory conditions (five constant temperatures i.e., 22.5 ± 1, 25 ± 1, 27.5 ± 1, 30 ± 1 and 32.5 ± 1 °C 55 ± 5% relative humidity (R. H.) and a 16:8 h light: dark photoperiod). Total developmental time at the above-mentioned temperatures were 28.83 ± 0.17, 24.52 ± 0.37, 21,39 ± 0.21 17.92 ± 0.16 and 18.22 ± 0.29 days on S. cereallelaand27 ± 0.38, 23.32 ± 0.14, 19.57 ± 0.28, 16.14 ± 0.17 and 16.33 ± 0.05 days on E. kuehniella. The lower developmental thresholds (T0) of egg, larva, pupa and egg to adult on E. kuehniella were estimated15.02, 8.6, 7.48 and 8.55 ºC and the thermal constant for these periods calculated as 38.16, 222.22, 71.9 and 370.37 DD. The lower developmental thresholds on S. cereallela were found to be 13.79, 5.6, 5.82 and 6.54 ºC andthermal constant for the mentioned periods were 41.15, 277.77, 91.7, 454.54 DD, respectively. Although significant differences between developmental times at different temperatures exist, no significant differences was observed between 30 and 32.5 °C for two prey species. The results suggest that E. kuehniella serves as a more effective host than S. cereallela for rearing of coccinellid O. conglobata