shirin shahbazi

K-Ras mutations rarely occur in breast cancer. However, studies have supported that K-Ras upregulation is involved in breast cancer pathogenesis. Two main K-Ras transcript variants, K-Ras4A and K-Ras4B, arise originate from the alternative splicing of exon 4. In this study, we aimed to evaluate variations in the expression of K-Ras4A and K-Ras4B and their role in breast ductal carcinoma.

Total RNA was extracted from breast tumors, and the NATs were obtained via mastectomy. Patients were selected from new cases of breast cancer with no prior history of chemotherapy. Relative mRNA expression was calculated based on a pairwise comparison between the tumors and the NATs following normalization to the internal control gene. Predictive values of the transcript variants were examined by ROC curve analysis.

A statistically significant increase was found in K-Ras4A and K-Ras4B expression with the mean fold changes of 7.58 (p = 0.01) and 2.47 (p = 0.001), respectively. The K-Ras4A/K-Ras4B ratio was lower in the tumors than that of the normal tissues. ROC curve analysis revealed the potential of K-Ras4A (AUC: 0.769) and K-Ras4B (AUC: 0.688) in breast cancer prediction. There was also a significant association between K-Ras4B expression and HER2 statues (p = 0.04). Furthermore, a significant link was detected between K-Ras4A expression and pathological prognostic stages (p = 0.04).

Our findings reveal that the expression levels of K-Ras4A and
K-Ras4B is higher in the tumor compared to the normal breast tissues. Increase in K-Ras4A expression was more significant than that of K-Ras4B.

Gastric cancer is the fifth most common cancer and the fourth leading cause of cancer death in the world. This genetically heterogeneous condition can be sporadic or inherited as an autosomal trait. One of the most important causes of sporadic gastric cancer is environmental factors such as Helicobacter pylori infection. In recent decades, proton-pump inhibitors (PPIs) have been widely used to treat gastrointestinal problems. New researches raise concerns about the link between PPIs and gastric cancer. The CpG island methylator phenotype (CIMP) seen in various malignancies is a set of epigenetic changes associated with promoter methylation and down regulation of the tumor suppressor genes. The present study investigated the methylation profile of MINT2, MINT1, MINT25 and MINT31 promoter regions in patients with gastric cancer. The MINT1 gene, also known as Amyloid-beta A4 precursor protein-binding family A member 1 (APBA1), is located on 9q and encodes a protein which is involved in signal transduction processes. Studies have shown a significant increase in MINT1 hypermethylation in gastric cancer tissues significantly associated with Helicobacter pylori infection. The MINT2 gene, or Amyloid-beta A4 precursor protein-binding, family A, member 2 (APBA2), has been mapped to the 15q region. Abnormal methylation of MINT2 has been identified in the blood and peritoneal fluid of patients with gastric cancer suggesting that it can be used as a predictor of peritoneal micrometastasis. The next two gene regions, MINT25 and MINT31, are functionally different. In fact, MINT25 is the Matrix metalloproteinase 24 (MMP24) gene, located at 20q. Studies have shown that MINT25 hypermethylation is a specific molecular marker for gastric cancer screening. The MINT31 marker is located at 17q in the non-coding region upstream of the CACNA1G gene, which is a T-Type Calcium Channel. MINT31 plays an important role in regulating CACNA1G expression. Studies have shown that hypermethylation of the MINT31 region can be used as a predictor of gastric cancer progression. Based on these findings, the present study investigates the methylation profile of MINT2, MINT1, MINT25 and MINT31 promoter regions in patients with gastric cancer. Another goal of this project was to investigate the correlation between this methylation profile and patients' clinical characteristics.

In this descriptive-analytical study, patients with adenocarcinoma gastric cancer between the ages of 50 and 85 years old were studied. The age matched control group included non-cancerous gastrointestinal patients who referred for endoscopy. Tumor and control tissue samples were collected by endoscopy. Collected tissue samples were extracted using the GENTBIO kit and DNA samples were kept at -20. Methylation-specific PCR (MSP) was used to determine the methylation pattern of selected gene regions. Bisulfite treatment was performed by Bisulfite Conversion Kit (ZYMO RESEARCH). Briefly, bisulfite solutions were prepared according to the kit instructions and were added to the samples. The mixtures were incubated for 5 hours then centrifugation was performed. In the next step a combination of BL buffer and carrier RNA were added to the products. The samples were then thoroughly mixed with ethanol and transferred to Epitect columns. BW wash buffer and BD desulfurizing buffer were used in later stages to improve DNA quality. For each reaction of PCR we used 2X PCR-master mix, 0.5µl of each forward and reverse primers with a concentration of 10μM and 50ng DNA. The following temperature program was applied: 15 minutes at 95°C, 35 cycles including 20 seconds at 95 °C, 30 seconds annealing with variable and specific temperature for each pair of primers, extension for 25 seconds at 72°C and final extension for 5 minutes at 72°C. The annealing temperature of the primer pairs was standardized between 51-60°C. PCR products were evaluated by 8% polyacrylamide gel stained with silver nitrate. After collecting and extracting the results, the data were analyzed using SPSS software version 19. P value less than 0.05 was considered significant.

Methylation profile of MINT2, MINT1, MINT25 and MINT31 promoter regions was assessed on polyacrylamide gel after treatment with bisulfite and MS-PCR. Each gene was amplified by a pair of primers for methylated (M) and a pair of primers for non-methylated (U) regions. In case of positive methylation of one or two genes, the situation was considered CIMP-Low phenotype and in case of positive methylation of 3 or 4 genes, phenotype was recorded as a CIMP-High. If the methylation of all four genes was negative, the CIMP-Negative phenotype was recorded. The results showed that CIMP was positive in 52.9% of gastric adenocarcinoma tissues, which included 41.2% CIMP-Low and 11.7% CIMP-High. MINT25 with 76% positive had the highest methylation rate. Interestingly, no positive cases of MINT25 were observed in the control group which could confirm the specificity of this marker. MINT31 was next with 53% positive cases. In control samples for three promoter regions, methylation results were negative and only two positive cases were observed regarding MINT31. MINT1 and MINT2 genes were evaluated positive in 17.7% and 11.8% of cases, respectively. According to these results, there was a statistically significant correlation between PPIs and methylation of MINT25 and MINT31 promoter regions. Considering all 4 gene regions as CIMP phenotype, the significance of the results was reduced, which could be due to the low sample size of positive cases in MINT1 and MINT2. Contrary to expectations, no significant link was observed between the Helicobacter pylori infection and methylation of each gene alone. However, the CIMP-Positive phenotype showed a stronger association with Helicobacter pylori infection than individual genes, although this association was not reached the significant level.

Gastric cancer is a multifactorial disease that despite the discovery of several predisposing genes, scientific evidence still indicates the important role of environmental factors in its development. Studies have shown the effective role of epigenetic changes in gastric carcinogenesis. Methylation of many genes has been studied in gastrointestinal cancers, including gastric cancer. Epigenetic instability, characterized by hypermethylation of multiple CpG islands, is known as the CIMP phenotype. CIMP-positive tumors indicate that hypermethylation has occurred simultaneously in the promoter regions of several tumor suppressor genes. This leads to inactivation of gene transcription and consequent loss of their function. So far, different gene sets have been selected to study CIMP in a variety of cancers, due to the heterogeneity of histological features in tumors and patient populations. In the present study, the promoter regions of MINT1, MINT2, MINT25 and MINT31 in patients with gastric cancer were examined and the results confirmed the presence of CIMP-Low and CIMP-High phenotypes in these samples. In our study, the correlation between methylation pattern and clinical characteristics of patients was also investigated. Statistical analyzes showed a significant link between methylation of MINT25 and MINT31 promoter regions with the PPIs. Evidence from several studies suggests that long-term use of PPIs is associated with a higher risk of gastric cancer. However, some studies have suggested that this risk may be limited to people with a history of Helicobacter pylori infection or precancerous lesions of the stomach. Because PPIs induce hypergastrinemia and cellular hyperplasia, they could increase the risk of gastric cancer. Overall, the results of our study show that the CIMP phenotype can be introduced as a biomarker in the diagnosis of gastric cancer, although the methylation profile selection should be standardized based on the characteristics of each population. The results of our study showed that among the 4 proposed gene regions, MINT25 has a statistically significant correlation with gastric cancer and also with a history of PPIs, which indicates the importance of studying this marker in Iranian patients with gastric cancer.

  Fragile X-associated premature ovarian insufficiency is clinically defined as a type of early ovarian failure with irregular menstrual cycles, increased follicle-stimulating hormone, premature menopause, and infertility. Genetically, the CGG trinucleotide repeat expansion in the 5'-untranslated region of the FMR1 gene is recognized as a causative factor. The aim of this study was to standardize molecular detection methods and estimate the number of repeats among patients with premature ovarian insufficiency.

 After obtaining a consent form and blood sampling, genomic DNA was extracted and treated with sodium bisulfite. The FMR1 gene is located on X chromosome and one allele is methylated by X-inactivation. As a result, the methylation-specific polymerase chain reaction (MS-PCR) was performed using two pairs of specific primers for methylated and non-methylated DNA yelding the products of 108+3n and 168+3n bp, respectively. Following clinical evaluations, 20 sporadic patients and two families with at least two patients were studied.

 The mean level of follicle-stimulating hormone was 85.45±44.73UI/L in sporadic and 75.72±33.61UI/L in familial cases. Ultrasound examinations reported atrophic ovaries in sporadic and familial cases by 80% and 75%, respectively. The evaluation of the trinucleotide repeat expansions on agarose gels showed that two sporadic patients were carriers of FMR1 intermediate alleles (10%). No cases of pre-mutation or full mutation were observed in other sporadic or familial cases and the trinucleotide repeat expansions were estimated between 15 and 35.

 Due to the role of the FMR1 gene trinucleotide repeat expansion in women with premature ovarian insufficiency, a fast and cost-effective molecular detection method is of particular importance. This test will be beneficial not only in ovarian dysfunction, but also to identify pre-mutations that may expand in next generations leading to fragile X syndrome.

Practical Implications:

 In young women, the detection of expanded CGG trinucleotide repeats in the 5'-untranslated region of the FMR1 gene along with genetic counseling will provide them to plan reproductive life.

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.

Patient-centered care (PCC) is a valuable and logical concept in the nursing discipline. The aim of this study was to development and psychometrically evaluate a patient-centered care questionnaire in CICUs (PCC-CICUs).

This methodological study was performed in two phases. The first phase is the qualitative stage by grounded theory study in which, a literature review was carried out for tool development. The second phase includes a psychometric evaluation of the PCC-CICUs. The tool’s content validity was performed by skilled nurses in the field of patient-centered care. The reliability of the tool was assessed by Cronbach's alpha and its stability was measured by internal consistency and reliability. Exploratory factor analysis was used to determine the construct validity.

The PCC-CICUs was evaluated for validity and reliability. Exploratory factor analysis was used to assess the construct validity. The analysis led to the development of a tool with 28 items in four dimensions of patient and family empowerment, understanding the patient, skill and expertise, and respecting the patient and family, which accounted for 35.380% of the variance. Cronbach's alpha of the tool was 0.68. The test-retest method supported the stability of the instrument.

Patient-centered care questionnaire in cardiac intensive care units is a standard and accepted questionnaire to assess the amount of patient-centered care from the patients' point of view. Health care professionals can use the PCC-CICUs to assess their own and peers’ practice to detect potential areas for improvement in nursing care and help nurse managers with planning appropriate quality improvement programs.

Identification of underlying mechanisms of gliomas pathogenesis is of particular importance. The overexpression of PTX3 gene is profoundly implicated in glioma development. The RNA interference (RNAi)-based knockdown of target gene by means of double-stranded RNA molecules including siRNA can be harvested as a therapeutic tool for oncogene silencing. The present study aimed to induce apoptosis in U-87 glioma cell line by knockdown of PTX3 gene.

A variety of in silico methods were applied for siRNA design to silence PTX3 gene. Scoring of candidate siRNAs was performed according to design rules. The best siRNA against the PTX3 gene as well as scrambled siRNA were selected. The efficacy of PTX3 silencing in the U-87 cells was evaluated by Real‐time PCR assay. To assess the effect of PTX3 knock down on cellular apoptosis, the mortality rate of transfected cells was compared with control groups by flow cytometry.

Designed PTX3‐siRNAs (n=53) were assessed and scored from different aspects and the best one was suggested in PTX3 gene expression knockdown assay. The 72-hour treatment of U-87 cells with designed PTX3‐siRNA in 100 nM concentration affected the gene expression by decreasing to 69%. Flowcytometry results indicated the induction of apoptosis in 65% of the cells.

The efficiency of designed siRNA was approved in vitro, with significant effect on the downregulation of PTX3 gene and induction of apoptosis in U-87 glioma cells. Based on our finding, targeting PTX3 via siRNA can be considered as an anti-cancer strategy.

The aim of this study was to evaluate the effect of lysophosphatidic acid (LPA) on the follicular development, incidence of cell death, and expressions of apoptosis related genes and miR-22 in transplanted ovaries.

In this experimental study, three-week-old mice ovaries were cultured for 24 hours in the presence and absence of LPA, and we assessed cell survival and normal follicular rates in some of the cultured ovaries. The remaining cultured ovaries were autotransplanted in the presence and absence of LPA as four experimental groups (LPA-/LPA-, LPA-/LPA+, LPA+/LPA-, LPA+/LPA+). The follicular development, immunohistochemistry for BAX, and expressions of genes related to apoptosis and miR-22 by real time reverse transcription polymerase chain reaction (RTPCR) were studied at the first oestrous cycles in the recovered ovaries. Sera 17-β-oestradiol (E2) and progesterone (P4) levels were also assessed.

Both cell survival and normal follicular rates were significantly higher in cultured ovaries in the presence of LPA after 24 hours (P<0.05). There was an increase in follicular development in comparison with the intact control group in the four transplanted groups (P<0.05). The LPA+/LPA- group had significantly higher follicular development, a decline in BAX positive cells, and a decrease in pro-apoptotic gene expressions in parallel with enhanced expression of anti-apoptotic and miR-22 genes and higher levels of hormones compared with the non-treated and intact control groups (P<0.05).

LPA, as a survival factor, improves follicular development in transplanted ovaries by providing a balance between the anti- and pro-apoptotic genes in association with an increase in miR-22 expression.

Gastric cancer is a major public health issue as the fourth leading cause of cancer-related death in the world. Reactive oxygen species (ROS) induce DNA damage and this process plays an important role in gastric cancer development and progression. OGG1 is an essential component of the base excision repair pathway  that is required for the removal of oxidized guanine nucleotides from DNA exposed to ROS. This study aimed to compare the expression of the OGG1 gene in cancerous and healthy tissues of gastric cancer.

Fifty pairs of tumors and adjacent normal tissues were collected from gastric cancer patients. Total RNA was extracted and complementary DNA (cDNA) was synthesized. The relative gene expression of OGG1 was determined using quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR). A data mining study was also performed to determine the prognostic role of OGG1 expression in the overall survival of gastric cancer patients.

OGG1 gene expression was significantly increased in patients' tumor samples compared to normal adjacent tissue samples. In addition, the expression of OGG1 in patients with early stages of gastric cancer was significantly higher than those with advanced stages. Also, a negative correlation was observed between the high expression of OGG1 and the overall survival rate.

It can be concluded that the expression of OGG1 increases in the early stages of gastric cancer, which could be related to the increase in oxidative damage to DNA.

Mitochondria implement various cellular functions, including energy production through the electron transport chain by oxidative phosphorylation mechanism. These respiratory chains consist of several complexes and protein subunits which are encoded by nucl ear and mitochondrial genes. Due to mutation susceptibility and repair limitation, more aberrations have occurred in mitochondrial DNA in comparison to nuclear DNA. Given the fact that mitochondrial DNA lacks introns, mutations almost occur in the coding s equence, which comprises a direct impact on its functions. Emerging evidence indicates that mutations in the mitochondrial DNA led to the production of reactive oxygen species, disrupted apoptosis, and tumor development. Studies reported various somatic a nd germline variants in mitochondrial DNA related to tumorigenesis. The D - loop region which is the starting point for replication and transcription of mitochondrial DNA is the most prevalent site of somatic mutations in solid tumors. The D - loop mutations a lso cause copy number variations which are gaining interest in studies of solid tumors including breast cancer, colon cancer, hepatocellular carcinomas, and prostate cancer. Most studies have reported a mitochondrial DNA reduction which subsequently preven ts apoptosis and promotes metastasis. The mitochondrial DNA region - specific haplogroups are also involved in the sequence variations due to processes such as genetic drift and adaptive selection. This review article discusses the biology and function of mi tochondria and related genes. By explanation of mitochondrial dysfunction caused by different kinds of alterations, we attempt to elucidate the role of mitochondria in tumorigenesis. Prominently published articles in this field were reviewed and the role o f germline and somatic mutations of mitochondrial DNA have been investigated in common cancers.

The aim of this study was to evaluate the effect of lysophosphatidic acid (LPA) supplementation during in vitro culture and transplantation of mouse ovaries on the follicular development and expression of vascular endothelial growth factor (VEGF) as an angiogenesis factor at the mRNA and protein levels.

Three weeks old mice ovaries were cultured in the presence and absence of LPA for 24 hours, then they were capsulated in sodium alginate in the presence and absence of LPA as four experimental groups. After transplantation the vaginal smears were performed daily to evaluate the initiation of the estrous cycle. The morphology and follicular distribution were analyzed at the first and fourth estrous cycles using hematoxylin and eosin staining. Then in the groups that showed higher and lower follicular development the immunohistochemistry assay was conducted to identify VEGF protein expression, and the real time RT-PCR was done to analyze the expression of Vegf gene at the first estrus cycle.

The large size follicles and also the corpus luteum were prominent in all transplanted groups at fourth estrus cycle in comparison with intact control groups. The statistically lowest percentage of small size follicles and the highest percentages of large size follicles were seen in LPA+/LPA- group (p<0.05). The expression ratio of Vegf to β-actin was significantly higher in this group in comparison with non-LPA treated and intact control groups (p <0.05).

LPA as an angiogenesis factor increases the follicular development in transplanted ovaries but it causes early discharge of ovarian reserve.

Hypertrophic cardiomyopathy is a common genetic cardiovascular disease with autosomal dominant inheritance and MYBPC3 gene has been frequently linked to its pathogenesis. Since, carriers of the 25 nucleotides deletion located on intron 32 of the MYBPC3 are at increased risk of heart disease we aimed to investigate this variant in hypertrophic cardiomyopathy patients and healthy population.

DNA was extracted from 350 Blood samples including 42 hypertrophic cardiomyopathies and 308 healthy subjects and the region containing the deletion was amplified by PCR method. PCR products were analyzed on agarose gel and genotyping results were recorded.

Genetic counseling results revealed that 26.2% of patients were sporadic cases vs 59.5% with positive family history and there was a history of sudden cardiac death in the first degree relatives of 42.3% of the patients. Genotyping results showed that all samples had a single band of 198 bp, indicating no MYBPC3Δ25bp variant in HCM patients as well as 308 controls. Bioinformatics assessments revealed that MYBPC3Δ25bp had a frequency of 0.00438 on Iranome database with the highest incidence reported in the Baloch population.

Since hypertrophic cardiomyopathy is related to sudden cardiac death, population studies in terms of predisposing factors are of particular importance. Our study results showed that MYBPC3Δ25bpshould not be considered as risk factor in the patients of northwest of Iran. However, according to the bioinformatics findings and reports of neighboring countries, it is suggested that MYBPC3Δ25bp to be studied in the eastern and southern Iranian hypertrophic cardiomyopathy patients.

Several conflicting results have been reported on the survival and function of transplanted ovaries.

Evaluation of the follicular development and the expression of vascular endothelial growth factor (VEGF) and Bcl-2-associated X protein )BAX (in ovaries transplanted into uni- and bilaterally ovariectomized mice.

In this experimental study, 40 female NMRI mice (21-days-old, 12-15 gr) were ovariectomized uni- and bilaterally (n = 20/ group), while the 8-wk-old mice were considered as intact control group (n = 6). 5 weeks after transplantation at the proestrus stage, the morphology of recovered transplanted ovaries and the proportion of follicles were studied at different developmental stages. The apoptosis cell death by pro-apoptotic protein BAX and the expression of VEGF were evaluated using immunohistochemistry.

In the bilaterally ovariectomized mice, among the 455 counted normal follicles, a lower rate of primordial and primary follicles and a higher rate of preantral and antral follicles were observed (p = 0.002). However, the percentages of preantral and antral follicles, and the corpus luteum were significantly lower in the intact control group (among the 508 counted normal follicles in this group) compared to other transplanted groups (p = 0.002). The number of BAX-positive cells in all groups was not significantly different. The VEGF expression was prominent in vessels of the corpus luteum, and also in the theca layer of large follicles of studied groups.

Early discharge of ovarian reserve was prominent in the bilaterally ovariectomized group but the incidence of apoptotic cells and VEGF expression as angiogenic factor did not differ in both ovariectomized mice. Thus, unilaterally ovariectomy has less side effects on the ovarian reserve compared to bilateral ovariectomy.

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.

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.

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).

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

Invasive aspergillosis is a severe opportunistic infection with high mortality in immunocompromised patients. Recently, the roles of microRNAs have been taken into consideration in the immune system and inflammatory responses. Using bioinformatics approaches, we aimed to study the microRNAs related to invasive aspergillosis to understand the molecular pathways involved in the disease pathogenesis. Data were extracted from the gene expression omnibus (GEO) database. We proposed 3 differentially expressed genes; S100B, TDRD9 and TMTC1 related to pathogenesis of invasive aspergillosis. Using miRWalk 2.0 predictive tool, microRNAs that targeted the selected genes were identified. The roles of microRNAs were investigated by microRNA target prediction and molecular pathways analysis. The significance of combined expression changes in selected genes was analyzed by ROC curves study. Thirty-three microRNAs were identified as the common regulator of S100B, TDRD9 and TMTC1 genes. Several of them were previously reported in the pathogenesis of fungal infections including miR-132. Predicted microRNAs were involved in innate immune response as well as toll-like receptor signaling. Most of the microRNAs were also linked to platelet activation. The ROC chart in the combination mode of S100B/TMTC1, showed the sensitivity of 95.65 percent and the specificity of 69.23 percent. New approaches are needed for rapid and accurate detection of invasive aspergillosis. Given the pivotal signaling pathways involved, predicted microRNAs can be considered as the potential candidates of the disease diagnosis. Further investigation of the microRNAs expression changes and related pathways would lead to identifying the effective biomarkers for IA detection.

 To evaluate the birth weight and post-natal non-coagulation problems of infants of mothers with coagulopathies versus normal mothers.

 In a retrospective cohort study, 100 women with coagulation problems attended the Iranian Haemophilia Comprehensive Care Center, and 200 normal women attending two health centers in Tehran and Karaj, with a history of at least one pregnancy were studied. A questionnaire about mothers’ and neonates’ condition was filled out by an interview, and the data were analyzed using SPSS software, version 16.

 Using linear regression, the maternal coagulation problem had a negative effect on birth weight (p<0.001, β= -0.31). The prevalence of early and prolonged jaundice in newborns of mothers with coagulopathy was higher than that in newborns of normal mothers (12% vs. 2%, and 7% vs. 3%, respectively), the difference between the two groups in terms of incidence of early jaundice was statistically significant (chi square-p<0.001). The frequency of using phototherapy and blood exchange for treating neonatal jaundice, in neonates of mothers with coagulopathy was higher than in neonates of normal mothers (31% vs. 21% and 8% vs. 21%, respectively) (p<0.001). Furthermore, the duration of hospitalization, hospitalization in NICU, and re-hospitalization during the first month of life in neonates of mothers with coagulation problems was higher than in neonates of normal mothers (p<0.001).

 Considering the high prevalence of neonatal problems in newborns of mothers with coagulation problems and their lower birth weight, further care measures should be provided for them.

Overexpression of oncomir-21 promotes proliferation of breast cancer cells. This study aimed to assess the effect of endurance training on the expression of miR-21 and its downstream, Bcl2 and upstream targets, STAT3 in breast cancer bearing mice.

After orientation to the environment, breast cancer cells, MC4-L2 were injected to mice and they randomly were categorized into two groups, control (n=10) and training (n=10) groups. Training group performed progressive endurance training 5 days per week for 6 weeks and control group did not perform any exercise. Tumor volume was measured by a digital caliper every week. Finally, the mice were sacrificed; tumor tissue was removed and immediately frozen and kept in -70°C. RNA extraction and cDNA synthesis were carried out by trizol reagent and specific kits and level of genes were measured by quantitative real-time PCR.

Endurance training decreased significantly expression of miR-21, STAT3 and Bcl2 (P<0.05). In addition, Tumor volume developed further in control group compared to training group (P<0.05) . There was significantly positive correlation (P<0.001) between miR-21 with STAT3(R=0.66) and miR21 with Bcl2 (R=0.61)

Endurance training leads to suppress expression of STAT3/miR-21/Bcl2 signaling pathway, thereby involved in slow tumor growth. Therefore, one of the beneficial effects of endurance training on tumor progression in estrogen dependent mouse model of breast cancer is reducing intrtumor anti-apoptotic genes.

Menorrhagia is the most common type of abnormal uterine bleeding, caused by disruption of hormonal regulation, uterine function or blood clotting. Developing an effective diagnostic strategy will improve patient's quality of life and management. Here we investigated the links between hematological characteristics and prolonged menstruation‎ to estimate the importance of the first line coagulation screening tests in young women ‎.

 In a case-control design and under supervision of a specialist, 43 cases and 104 age matched controls were selected. Menstrual characteristics were evaluated by a standardized questionnaire distributed to high school and university young students. Hematological indices including first line coagulation screening tests were performed for both groups and statistically assessed.

Statistical analysis showed that prolonged menstrual bleeding ‎is significantly correlated to prolonged bleeding time (p value, 0.01) as well as ‏ red blood cell count (p value, 0.04). The O blood group showed the greatest contribution to the bleeding periods longer than 7 days (53.4 %(. Additional coagulation tests revealed one coagulation factor VII deficiency patient.

The results of the present study revealed the importance of menorrhagia management in young women and showed a significant correlation between prolonged menstrual bleeding ‎and blood types ‎. Our study findings also suggest a significant association between prolonged menstruation and bleeding time test, emphasizing on the role of blood coagulation traits in susceptibility to heavy menstrual bleeding.

Early diagnosis of prostate cancer (PCa) as the second most common cancer in men is not associated with precise and specific results. Thus, alternate methods with high specificity and sensitivity are needed for accurate and timely detection of PCa. MicroRNAs regulate the molecular pathways involved in cancer by targeting multiple genes. The aberrant expression of the microRNAs has been reported in different cancer types including PCa. In this bioinformatics study, we studied differential expression profiles of microRNAs and their target genes in four PCa gene expression omnibus (GEO) databases. PCa diagnostic biomarker candidates were investigated using bioinformatics tools for analysis of gene expression data, microRNA target prediction, pathway and GO annotation, as well as ROC curves. The results of this study revealed significant changes in the expression of 14 microRNAs and 40 relevant target genes, which ultimately composed four combination panels (miR-375+96+663/miR-133b+143-3p+205/ C2ORF72+ENTPD5+GLYAT11/LAMB3+NTNG2+TSLP) as candidate biomarkers capable to distinguish between PCa tumor samples and normal prostate tissue samples. These biomarkers may be suggested for a more accurate early diagnosis of PCa patients along with current diagnostic tests.

Coagulation factors belong to a family of plasma glycosylated proteins that should be activated for appropriate blood coagulation. Congenital deficiencies of these factors cause inheritable hemorrhagic diseases. Factor VII (FVII) deficiency is a rare bleeding disorder with variable clinical symptoms. Various mutations have been identified throughout the F7 gene and can affect all the protein domains. The results of previous experiments have partly revealed the correlation between genotype and phenotype in patients with FVII deficiency. Nevertheless, each particular variant may affect the coagulative function of FVII, mainly via altering its expression level, extra-cellular secretion, tissue factor binding affinity, or proteolytic activity. The pathogenicity of the variants and molecular mechanisms responsible for clinical symptoms in patients with FVII deficiency should be characterized via in silico and in vitro, as well as in vivo functional studies. This review has highlighted the most important functional studies reported on F7 gene variants, including relevant reports regarding Iranian FVII deficiency patients.

Considering the limitations of the common diagnostic test for prostate cancer prostate cancer, the introduction of higher-specific biomarkers for a more accurate and timely diagnosis of prostate cancer is desired. In this study, we aimed to investigate the miR-200 family (miR-200a, miR-200b, miR-200c, miR-141, and miR-429) and their target genes using bioinformatics prediction tools in order to propose potential diagnostic biomarkers for prostate cancer. In this theoretical study, based on bioinformatics study of micro RNA, the DIANA TOLLS-mirPath v.3 database was used to search the target genes of the miR-200 family in the signaling pathways known in prostate cancer pathogenesis. Then, we confirmed the suggested genes by the online predictive tools such as MiRWalk, Targetscan and RNAhybrid. Finally, the functional role of target genes was investigated on the DAIVID bioinformatics database. According to the results of this study, the E2F3 gene is the target of all family members of miR-200, BCL2 is the common target of miR-200b / miR-200c / miR-429 and CCNE2 is the common target of miR-200a / miR-141 subsets. Also, miR-200c and miR-429 can modulate the pathogenesis of prostate cancer by targeting CDKN1B and KRAS genes, respectively. The results of this study showed that members of the miR-200 family targeting the genes involved in important biological processes and molecular pathways of prostate cancer pathogenesis are likely to be effective diagnostic biomarkers in future experimental studies.

Although Malassezia genusare part of the skin normal flora, under certain conditions, they become pathogenic. Catheter-related fungemia, caused by Malassezia, which is associated with biofilm formation, is considered a nosocomial infection.
The aim of this study was to evaluate the ability of Malassezia globosa and Malassezia restricta in biofilm formation.
Biofilm formation was carried out using catheter segments in 12-well plates. Results were measured using 3-(4, 5- dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide (MTT) colorimetric assay in 96-well plates. The data was analyzed using univariate Analysis of Variance (ANOVA) or Repeated Measures ANOVA. P values of ≤ 0.05 were considered statistically significant. Statistical analyses were performed using IBM SPSS Statistics version 22.0 software.
Both M. globosa and M. restricta species were able to form biofilms in vitro. Malassezia restricta was more capable than M. globosa to form biofilms, yet, significant differences were not observed (P = 0.192).
Over time, Malassezia biofilms matured. Due to the above species ability in forming biofilm, they could play an important role in fungemia that should be considered in therapeutic procedures.

Labor pain is an unpleasant experience for most women and can affect their birth satisfaction. This study investigated the effects of ice pack application on pain intensity in the active phase of labor and on birth satisfaction among primiparous women.
Methods & Materials: This randomized controlled trial was conducted on ninety primiparous women. Participants were randomly allocated to either an intervention or a control group. In the intervention group, an ice pack was placed on the sacral area of each participant in the active phase of labor for ten minutes. This intervention was repeated every thirty minutes up to the beginning of the second stage of labor. In both groups, labor pain intensity was assessed before and every one hour after intervention onset and birth satisfaction was assessed 24 hours after delivery. Data were analyzed through the SPSS software (v. 22.0).
Groups did not significantly differ from each other respecting participants’ demographic and clinical characteristics. Throughout the study intervention, labor pain intensity increased in both groups; however, the increase in the control group was significantly greater than the intervention group (P Without any significant side effects, ice pack application can significantly reduce pain intensity during the active phase of labor. Thus, this intervention is recommended for labor pain alleviation.

The aim of this study was to determine the effects of aerobic interval training and the purported antioxidant treatment, selenium nanoparticle supplementation on the expression of autophagy in 4T1 breast cancer-bearing mice with cachexia. 3-5 weeks old Balb/c mice were initially assigned to control, interval training, selenium nanoparticles and interval training-selenium nanoparticles (n = 15–16/group). After 6 weeks of training, half of each group was injected with 4T1 tumor cells, followed by 6 additional weeks of training. Finally, the mice were sacrificed, tissues were removed and were quantified using the Real-time PCR method. The effect of exercise training on the expression of LC3 and the effect of cancer on mTOR is significant. Combination of interval training and selenium nanoparticles maintained skeletal muscle function in cancer (P<0.05). finally, the adaptation of autophagic genes against physiological and pathologic stresses can be considered to be a counterbalance in body effort to modify these conditions and to bring the body to physiological homeostasis.

The importance of Candida albicans as the most common cause of fungal infections in humans is undeniable. Genotyping methods have been developed as useful tools to differentiate between fungal strains isolated from various infections. Several molecular typing methods have been described for C. albicans, and fragment length analysis of microsatellites called microsatellite fragment length polymorphism (MLP) is one of the most accurate genotyping methods.
The present study aimed at evaluating the genetic diversity and genetic relationships among C. albicans isolates recovered from HIV-positive patients with oral candidiasis in Iran using MLP.
We analyzed 30 isolates of C. albicans obtained from HIV-positive patients in Tehran. Genotypes of C. albicans isolates associated with oropharyngeal candidiasis were determined using microsatellite length polymorphism analysis. Three loci including EF3, CDC3, and HIS3 were amplified using multiplex PCR. After amplification, the product was run on an automated single-capillary genetic analyzer, and band sizes (known as alleles) were calculated with gene scan mapper.
PCR MLP typing of the 30 isolates under study yielded 27 different profiles, and the discriminatory power index was obtained as 0.993. Ten alleles and 18 different combinations were detected for the EF3 gene, 7 alleles and 18 combinations for the EF3 gene, and 10 alleles and 14 combinations for the HIS3 gene. Only 2 isolates were homozygous in all the 3 loci. To identify the origin of superficial infections in 6 patients, C. albicans isolates from the superficial as well as oral samples were simultaneously genotyped. Results showed the identity of genotypes in 4 of these patients. For 1 patient, the C. albicans genotype of the nails was different from the genotype observed in the oral cavity, which raised the possibility of an exogenous source for the superficial infection. Also, there were changes at only 1 or 2 alleles, which represented microevolution in some isolates.
The high variation of genotypes throughout the population of C. albicans suggested that the microsatellite fragment length polymorphism using multiplex PCR-based system provided high-speed genotyping, indicating its usefulness in molecular epidemiological evaluation.