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Background: In Iran, lung cancer is the third most common type of cancer and its prevalence is increasing rapidly. Identification informative genetic polymorphisms in cancer causing genes including epidermal growth factor receptor (EGFR) as key gene in control of cellular proliferation via intrinsic tyrosine/kinase activity, exonuclease 1 (EXO1) as one of the upregulated gene in different human malignancies and leptin (LEP) participate in carcinogenesis in lung cancer appears to be used as potential genetic markers for predicting lung cancer risk. There is no study about investigate association of the EGFR (− 216G/T), Exo1 (K589E) and LEP (− 2548G/A) gene polymorphisms with risk of lung cancer in Iranian population. The aim of this study was investigating the association of EGFR (− 216G/T), Exo1 (K589E) and LEP (− 2548G/A) gene polymorphisms with risk of lung cancer as a potentially diagnostic biomarker in Iranian population. Methods: In this case–control study, A total of 100 patients with lung cancer and 100 age and gender-matched healthy controls were recruited into this study and the association between EGFR (− 216G/T), Exo1 (K589E) and LEP (− 2548G/A) gene polymorphisms with the risk of lung cancer was investigated by using PCR–RFLP technique and bioinformatics approach. Results: The rs712829 of EGFR gene show that a significant statistical difference between G allele and risk of lung cancer (P = 0.001, OR = 2.976, CI = 95%, 1.557–5.691), in contrast, the T allele and TT genotype show a protective role against the risk of lung cancer. Result of in silico analysis indicated that the rs712829 alter splicing and promoter regulation of EGFR gene and associated with the risk of lung cancer. PCR–RFLP result for rs1047840 of Exo1 gene showed that the AA genotype and A allele of this polymorphism associated with risk of lung cancer, whereas the GG genotype show a protective effect against the risk of lung cancer (P = 0.004, OR = 5.391, CI = 95%, 1.690–17.200). On the other hand, in silico analysis showed that the existence of rs1047840 in Exo1 gene influence lung cancer susceptibility. For rs7799039 of LEP gene, PCR–RFLP analysis showed that, there is no significant association between this polymorphism and the risk of lung cancer. Conclusion: The rs712829 of EGFR gene and rs1047840 of Exo1 are associated with risk of lung cancer among Iranian population and can be used as a potentially candidate biomarker for early detection and primary prevention. [ABSTRACT FROM AUTHOR]

Background: Human growth hormone (hGH) plays a crucial role in growth by binding to growth hormone receptor (GHR) in target cells. Binding of GH molecules to their cognate receptors triggers downstream signaling pathways leading to the transcription of several genes, including insulin-like growth factor (IGF)-1. Pathogenic variants in the GHR gene can result in structural and functional defects in the GHR protein, leading to Laron Syndrome (LS) with the primary clinical manifestation of short stature. So far, around 100 GHR variants have been reported, mostly biallelic, as causing LS. Case presentation: We report on three siblings from an Iranian consanguineous family who presented with dwarfism. Whole-exome sequencing (WES) was performed on the proband, revealing a novel homozygous missense variant in the GHR gene (NM_000163.5; c.610 T > A, p.(Trp204Arg)) classified as a likely pathogenic variant according to the recommendation of the American College of Medical Genetics (ACMG). Co-segregation analysis was investigated using Sanger sequencing. Conclusions: To date, approximately 400–500 LS cases with GHR biallelic variants, out of them 10 patients originating from Iran, have been described in the literature. Given the high rate of consanguineous marriages in the Iranian population, the frequency of LS is expected to be higher, which might be explained by undiagnosed cases. Early diagnosis of LS is very important, as treatment is available for this condition. [ABSTRACT FROM AUTHOR]

Background: The Human Epidermal growth factor Receptor-3 (HER-3) is a member of ErbB receptor family and has deficient kinase activity. HER-3 should heterodimerize with other members of ErbB receptor family, especially with HER-2, to transduce downstream signaling pathways. HER-3 co-expresses with other ErbB receptors in different cancers and overexpresses while the oncogenic signaling pathways such as Jak/Stat, MAPK, and PI3K/Akt are activated and promoted. Here, the expression level of HER-3 was evaluated in Iranian gastric adenocarcinoma's patients and the effects of HER-3 knocking down was investigated on cell cycle and cell viability of human gastric adenocarcinoma cell line of MKN45. Methods: In this study, 38 paraffin-embedded surgical adenocarcinoma specimens and their marginal non-tumor tissue samples were collected. Total RNAs were extracted and cDNAs were synthesized. Finally, the expression level of HER-3 was evaluated by real time PCR approach. Moreover, the human adenocarcinoma cell line of MKN45 was transfected with siRNA against HER-3 and the effects of its down-regulation were evaluated using MTT assay and cell-cycle analysis. Results: The data obtained from this study revealed HER-3 is significantly overexpressed in gastric tumors rather than non-tumor marginal tissues. Also, it was found that the expression level of HER-3 is elevated with tumor depth of invasion. Moreover, HER-3 knocking down promotes cell accumulation in G2/M phase of cell cycle and decreases cell viability in MKN45 cells which suggests a potential role for HER-3 in gastric adenocarcinoma tumorigenesis. Conclusion: Taken together, these results emphasize the importance of HER-3 receptor in diagnosis and prognosis of gastric adenocarcinoma. [ABSTRACT FROM AUTHOR]

Identification of selection signatures may provide a better understanding of domestication process and candidate genes contributing to this process. In this study, two populations of domestic and wild goats from Iran were analyzed to identify selection signatures. RSB, iHS, and XP‐EHH statistics were used in order to identify robust selection signatures in the goat genome. Genotype data of domestic and wild goats from the NextGen project was used. The data was related to 18 Capra aegagrus (wild goat) and 20 Capra hircus (domestic goat) from Iran. The iHS method indicated 675 and 441 selection signatures in C. aegagrus and C. hircus, respectively. RSB and XP‐EHH methods showed about 370 and 447 selection signatures in C. aegagrus and C. hircus, respectively. These selection signatures were mainly associated with milk production, fleece trait, mammary epithelial cells, reproduction, and immune system. [ABSTRACT FROM AUTHOR]

Background: The B-cell-specific Moloney murine leukemia virus integration site1 (BMI-1) is one of the famous members of the Polycomb ring finger group, which plays a crucial role in the gene transcription regulation through histone changes. Hence, it is believed to be necessary to further clarify the effects of the BMI-1 clinical. Method: This cross-sectional study was conducted on 70 acute myeloid leukemia (AML), 70 chronic myeloid leukemia (CML), and 20 healthy individuals, as the control group. We used real-time quantitative polymerase chain reaction in order to assess the BMI-1 level expression and its effect on prognosis in AML patients in the Molecular Pathology Research Center. Results: The results of the present work indicated that the BMI-1 overexpression was significantly higher in the AML and CML patients compared with that in the healthy controls (P < 0.001). Furthermore, a significant relationship was observed between the BMI-1 overexpression and poor prognosis in the AML patients (Hazard ratio=1.749, P < 0.001, 95% confidence interval = 1.31-2.32). Additionally, BMI-1 high was found in chronic and blastic phase in the CML patients (P < 0.001). Conclusion: We concluded that investigation of BMI-1 gene expression pattern will be conducive to the prognosis and treatment of myeloid leukemia. [ABSTRACT FROM AUTHOR]

Background & Objective: Iran is located in the esophageal cancer geographical belt. As multiple genetic alterations are responsible for the molecular pathogenesis of esophageal squamous cell cancer (ESCC), the role and frequency of HER2 expression, MMR deficiency, and PI3KCA mutation are not well defined. Methods: We carried out HER2/neu expression, dMMR/MSI high, and PI3KCA mutation analysis in specimens of patients with ESCC. We accessed archival tissue blocks related to specimens of 68 ESCC cases at the time of surgery following neoadjuvant chemoradiation. These patients underwent surgery during 2013-2018 at the Cancer Institute of Iran affiliated with the Tehran University of Medical Sciences in Tehran. Results: None of the patients showed HER2 expression, dMMR/MSI high, or PI3K mutations. Conclusion: dMMR/MSI-H and PI3KCA mutation and HER2 expression may not be reliable andfrequent targets for systemic therapy in patients with esophageal SCC. [ABSTRACT FROM AUTHOR]

Background: Amplification of HER2 is an important factor in the diagnosis and treatment of breast cancer. Fluorescence in situ hybridization (FISH) is the gold standard for the detection of HER2-positive tumors. However, the Immunohistochemistry (IHC) assay for the detection of HER2 is more popular in the preclinical laboratory since it is faster and more economical compared to the FISH test. Materials and Methods: In this study, the status of HER2 amplification is determined by the FISH test using 44 formalin-fixed paraffin-embedded tissue samples and comparing the results with the IHC test to determine the reliability of the IHC test. Also, the relationship between HER2 amplification and estrogen, progesterone receptors, P53, age, menopausal status, family history of breast cancer, tumor size, and histological grade were determined. Results: Examination of HER2 in 44 samples by IHC showed 3 (6.8%) and 5 (11.4%) samples were positive (IHC 3+) and negative (IHC 0, 1+), respectively, and 36 (81.8%) samples were ambiguous (IHC 2 +), but examination by FISH showed 21 samples (47, 7%) were positive and 23 samples (52, 3%) were negative. There was a significant difference between IHC and FISH in the detection of HER2 amplification (P=0.019). Also, there was a significant difference between HER2 amplification and menopause in patients (P=0.035). Conclusion: This result demonstrated that the IHC test is not a reliable test to determine HER2 amplification. This study represented that FISH analysis is more reliable than IHC and must be preferentially performed for all cases, especially for HER2 +2 cases for whom the IHC result is 2+. [ABSTRACT FROM AUTHOR]

Background: Foeniculum vulgare, F. vulgare, commonly known as fennel, is believed to be one of the world's oldest medicinal herbs and has been exploited by people for centuries as a nutritional aid for digestive disorders. In many southeast Asian countries, it is ingested as an after-meal snack, mukhvas, due to its breath-freshening and digestive aid properties. F. vulgare is used in some countries, such as Iran, as a complementary and alternative treatment for inflammatory bowel disease (IBD). Methods: This study investigated the effects of fennel seed extract on intestinal epithelium barrier function and the Signal Transducer and Activator of Transcription (STAT) pathway. This pathway is active in inflammatory bowel disease. To study the protective effects of fennel seed extract in vitro, monolayers derived from the T84 colonic cell line were challenged with interferon-gamma (IFN-γ) and monitored with and without fennel seed extract. To complement our in vitro studies, the dextran sodium sulfate induced murine colitis model was employed to ascertain whether the protective effect of fennel seed extract can be recapitulated in vivo. Results: Fennel seed extract was shown to exert a protective effect on transepithelial electrical resistance (TEER) in both T84 and murine models and showed increases in tight junction-associated mRNA in T84 cell monolayers. Both models demonstrated significant decreases in phosphorylated STAT1 (pSTAT1), indicating reduced activation of the STAT pathway. Additionally, mice treated with fennel seed showed significantly lower ulcer indices than control mice. Conclusions: We conclude barrier function of the gastrointestinal tract is improved by fennel seed extract, suggesting the potential utility of this agent as an alternative or adjunctive therapy in IBD. [ABSTRACT FROM AUTHOR]

The present study aimed to improve the accuracy of genomic prediction of 16 agronomic traits in a diverse bread wheat (Triticum aestivum L.) germplasm under terminal drought stress and well-watered conditions in semi-arid environments. An association panel including 87 bread wheat cultivars and 199 landraces from Iran bread wheat germplasm was planted under two irrigation systems in semi-arid climate zones. The whole association panel was genotyped with 9047 single nucleotide polymorphism markers using the genotyping-by-sequencing method. A number of 23 marker-trait associations were selected for traits under each condition, whereas 17 marker-trait associations were common between terminal drought stress and well-watered conditions. The identified marker-trait associations were mostly single nucleotide polymorphisms with minor allele effects. This study examined the effect of population structure, genomic selection method (ridge regression-best linear unbiased prediction, genomic best-linear unbiased predictions, and Bayesian ridge regression), training set size, and type of marker set on genomic prediction accuracy. The prediction accuracies were low (-0.32) to moderate (0.52). A marker set including 93 significant markers identified through genome-wide association studies with P values ≤ 0.001 increased the genomic prediction accuracy for all traits under both conditions. This study concluded that obtaining the highest genomic prediction accuracy depends on the extent of linkage disequilibrium, the genetic architecture of trait, genetic diversity of the population, and the genomic selection method. The results encouraged the integration of genome-wide association study and genomic selection to enhance genomic prediction accuracy in applied breeding programs. [ABSTRACT FROM AUTHOR]

We aimed to study dietary patterns in association with the relative expression levels of PPAR-γ, vascular endothelial growth factor-A (VEGF-A) and hypoxia-inducible factor-1α (HIF-1α) in women with benign breast disease (BBD). The study design was combinative, included a case-series and case–control compartments. Initially, eligible BBD patients (n 77, aged 19–52 years old) were recruited at Nour-Nejat hospital, Tabriz, Iran (2012–2014). A hospital-based group of healthy controls was matched for age (n 231, aged 20–63 years old) and sex. Dietary data were collected using a valid 136-item FFQ. Principal component analysis generated two main components (Kaiser–Meyer–Olkin = 0·684), including a Healthy pattern (whole bread, fruits, vegetables, vegetable oils, legumes, spices, seafood, low-fat meat, skinless poultry, low-fat dairy products, nuts and seeds) and a Western pattern (starchy foods, high-fat meat and poultry, high-fat dairy products, hydrogenated fat, fast food, salt and sweets). High adherence to the Western pattern increased the risk of BBD (ORadj 5·59; 95 % CI 2·06, 15·10; P < 0·01), whereas high intake of the Healthy pattern was associated with a 74 % lower risk of BBD (95 % CI 0·08, 0·81; P < 0·05). In the BBD population, the Western pattern was correlated with over-expression of HIF-1α (radj 0·309, P < 0·05). There were inverse correlations between the Healthy pattern and expressions of PPAR-γ (radj −0·338, P < 0·05), HIF-1α (radj −0·340, P < 0·05) and VEGF-A (radj −0·286, P < 0·05). In conclusion, new findings suggested that the Healthy pattern was associated inversely with the risk of BBD, and this could be correlated with down-regulation of PPAR-γ, VEGF-A and HIF-1α genes, which might hold promise to preclude BBD of malignant pathological transformation. [ABSTRACT FROM AUTHOR]

Background & Objective: The her2 amplification plays an important role in breast cancer management. Therefore, there is a need for using supplementary molecular methods in IHC equivocal cases. Present study has been conducted to determine the effects of clinicopathological variables on her2 gene amplification by chromogenic in situ hybridization (CISH) in IHC Her2 (2+) breast cancer individuals. Methods: A cross-sectional study was conducted in Zaferanyeh Laboratory collaborated with Shahid Beheshti University of Medical Sciences (Tehran-Iran; 2015-2018). All pathological data related invasive breast cancer patients with equivocal IHC results were included. CISH method was performed as a supplementary technique. The associations between histopathologic variables, status of Ki-67 index, progesterone and estrogen receptors (PR & ER) with her2 amplification by CISH were investigated and analyzed. The level of significance was considered as P-value < 0.05. Results: Totally, 239 patients with mean age of 53.2 years were studied. CISH identified her2 gene amplification in 51 subjects (21.3%). The type of tumor (invasive ductal carcinoma), the tumor grade, and the value of Ki-67 index were directly correlated with her2 amplification. Significant negative associations were also observed between CISH results and ER and PR expression. Conclusion: As her2 gene amplification was identified in 21.3% of invasive breast cancer patients with equivocal IHC results, it is supposed that applying CISH method may consider as a potentially valuable supplementary method. Results have also shown that higher grades of tumor, invasive ductal carcinoma, absences of hormone receptors and high Ki-67 index significantly correlated with the her2 amplification. [ABSTRACT FROM AUTHOR]

Background and Aim Pregnancy and exercise training are associated with changes in the cardiovascular anatomy and physiology. There is a few studies on this issue in Iran. In this regard, the aim of this study is to assess the effect of a combined exercise training program on blood pressure and heart rate variability of pregnant women. Methods & Materials This randomized clinical trial was conducted in Shahid Akbarabadi Hospital in Tehran, Iran in 2019. Participants were 10 healthy pregnant women with a gestational age of 24-26 weeks in the interventional group and 10 healthy pregnant women in the control group. The interventional group received 8 weeks of combined exercise training at moderate intensity. The blood pressure measurement, electrocardiogram and aerobic and resistant exercise tests of samples were performed before and after training. AST3000 Avicenna software was used to analyze the heart rate variability parameters, and for statistical analysis, paired and independent t-tests, Mann Whitney U, and Wilcoxon tests were used. Ethical Considerations This study with registered clinical trial Code IRCT20190227042856N1 was approved by the Research Ethics Committee of Islamic Azad University of Science and Research Branch in Tehran, Iran (Code: IR.IAU.SRB.REC.1397.101). Results The mean systolic and diastolic blood pressure levels were lower in the interventional group by the 34th week of pregnancy compared to the control group (P<0.05). The mean of time-domain parameters in the interventional group were higher by the 34th week of pregnancy compared to the control group (P<0.05). Conclusion Combined exercise training can improve autonomic and parasympathetic nervous systems in pregnant women. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to evaluate the distribution of PIK3CA E545K mutation in Iranian CRC patients and explored its roles in disease prognosis. Background: Deregulation of the phosphoinositide 3-kinase (PI3K) pathway contributes to the progression of tumors. The p110a (PIK3CA), a catalytic subunit of PIK3, is mutated in many types of cancers. Exon 9 (E545K) is the most frequently mutated hotspot in PIK3CA in colorectal cancer (CRC). However, the prognostic role of PIK3CA E545K mutation needs to be elucidated. Methods: Tumors from 187 CRC patients were retrospectively collected from the Taleghani and Shohada Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran, between 2010 and 2017. PIK3CA E545K status was detected in Formalin-fixed paraffin-embedded (FFPE) tissues using PCR-RFLP methods, and validated by pyrosequencing. Correlations between PIK3CA E545K mutation clinicopathological features were analyzed. Results: The frequency of PIK3CA E545K gene mutations in CRC patients was 10.7%. Significant correlations were observed in PIK3CA E545K mutation with tumor differentiation and TNM stage (p < 0.042 and p = 0.033, respectively). Kaplan-Meier analysis showed a worse prognosis in overall survival (OS) in patients with PIK3CA E545K mutation (p < 0.001). Multivariate analysis indicated that PIK3CA E545K mutation was a detrimental factor for OS (HR = 6.497, 95% CI: 2.859-14.768, p < 0.021). Conclusion: A high frequency of PIK3CA E545K mutation was detected in Iranian CRC patients. The results of the present study suggested that PIK3CA E545K mutation may be associated with poor prognosis. These findings require further confirmation via prospective studies with larger samples. [ABSTRACT FROM AUTHOR]

Background: It is well known that normal pregnancy exposes mothers to a diabetogenic state. The important role of adipose tissue in the regulation of insulin resistance has been repeatedly proven. This organ carries out the regulation of insulin resistance by producing adipocytokines involved in the pathogenesis of gestational diabetes mellitus (GDM). The present study aims to evaluate the effects of zinc supplementation on serum leptin, visfatin, tumor necrosis factor-α (TNF-α), adiponectin and zinc-α2-glycoprotein (ZAG) levels in pregnant women with impaired glucose tolerance test (IGTT) results. Methods: In this randomized, placebo-controlled, double-blind clinical trial, 46 pregnant women with impaired glucose tolerance test results were randomly distributed into zinc (n = 23) and placebo (n = 23) groups and received 30 mg zinc supplement per day in the form of zinc gluconate and placebo, respectively, for 8 consecutive weeks. The study was conducted in the Shabestar district of northwestern Iran. Results: Supplementation after adjusting for confounding variables resulted in a significant reduction in plasma leptin (p = 0.035) and TNF-α (p = 0.027) levels in the zinc group compared with the placebo group. Serum visfatin levels were significantly increased, and serum ZAG levels were significantly decreased in both groups. However, the changes in adiponectin concentration were not significant in either group after intervention nor were the anthropometric parameters in fetuses whose mothers received the zinc supplement. Conclusions: It seems that zinc supplementation may be considered as a complementary supplement together with the medical management of patients with IGT or GDM. However, further studies are needed before definite conclusions can be drawn. [ABSTRACT FROM AUTHOR]

Salt stress is one of the major adverse environmental factors limiting crop productivity. Considering Iran as one of the bread wheat origins, we sequenced root transcriptome of an Iranian salt tolerant cultivar, Arg, under salt stress to extend our knowledge of the molecular basis of salinity tolerance in Triticum aestivum. RNA sequencing resulted in more than 113 million reads and about 104013 genes were obtained, among which 26171 novel transcripts were identified. A comparison of abundances showed that 5128 genes were differentially expressed due to salt stress. The differentially expressed genes (DEGs) were annotated with Gene Ontology terms, and the key pathways were identified using Kyoto Encyclopedia of Gene and Genomes (KEGG) pathway mapping. The DEGs could be classified into 227 KEGG pathways among which transporters, phenylpropanoid biosynthesis, transcription factors, glycosyltransferases, glutathione metabolism and plant hormone signal transduction represented the most significant pathways. Furthermore, the expression pattern of nine genes involved in salt stress response was compared between the salt tolerant (Arg) and susceptible (Moghan3) cultivars. A panel of novel genes and transcripts is found in this research to be differentially expressed under salinity in Arg cultivar and a model is proposed for salt stress response in this salt tolerant cultivar of wheat employing the DEGs. The achieved results can be beneficial for better understanding and improvement of salt tolerance in wheat. [ABSTRACT FROM AUTHOR]

Background: Maize Iranian mosaic virus (MIMV, genus Nucleorhabdovirus, family Rhabdoviridae) causes an economically important disease in maize and other gramineous crops in Iran. MIMV negative-sense RNA genome sequence of 12,426 nucleotides has recently been completed. Maize Genetics and Genomics database shows that 39,498 coding genes and 4,976 non-coding genes of maize have been determined, but still some transcripts could not be annotated. The molecular host cell responses of maize to MIMV infection including differential gene expression have so far not been elucidated. Methodology/Principal findings: Complementary DNA libraries were prepared from total RNA of MIMV-infected and mock-inoculated maize leaves and sequenced using Illumina HiSeq 2500. Cleaned raw transcript reads from MIMV-infected maize were mapped to reads from uninfected maize and to a maize reference genome. Differentially expressed transcripts were characterized by gene ontology and biochemical pathway analyses. Transcriptome data for selected genes were validated by real-time quantitative PCR. Conclusion/Significance: Approximately 42 million clean reads for each treatment were obtained. In MIMV-infected maize compared to uninfected plants, 1689 transcripts were up-regulated and 213 transcripts were down-regulated. In response to MIMV infection, several pathways were activated in maize including immune receptor signaling, metabolic pathways, RNA silencing, hormone-mediated pathways, protein degradation, protein kinase and ATP binding activity, and fatty acid metabolism. Also, several transcripts including those encoding hydrophobic protein RCI2B, adenosylmethionine decarboxylase NAC transcription factor and nucleic acid binding, leucine-rich repeat, heat shock protein, 26S proteasome, oxidoreductases and endonuclease activity protein were up-regulated. These data will contribute to the identification of genes and pathways involved in plant-virus interactions that may serve as future targets for improved disease control. [ABSTRACT FROM AUTHOR]

Background and Objectives: Polycystic ovary syndrome (PCOS) is the greatest current endocrine disease in generative women. Although other issues such as insulin resistance, hyperinsulinemia, adiposity and dietary pattern are implied to be connected to PCOS, but the most recent evidence are needed to improve management of PCOS. Proteins and amino acids (key dietary components) can also have impact on this condition and may have therapeutic effects for handling this disorder. However, there is little information available in this area. So, the purpose of this study was to assess the connection between amino acids and protein intake and PCOS. Materials and Methods: Science, Iran. Amino acids and proteins intake was estimated using validated food frequency questionnaire. Other factors such as ovarian disease, inherited predisposition, physical activity, the age of menarche and medical history were assessed by the questionnaire. Data analysis was represented by adjusted logistic by SPSS software version 15. Results: The marked association among PCOS and ovarian disease (P < 0.001), age (P < 0.001) and consuming drugs (P = 0.001) were seen. There was inversely associated between body mass index (BMI) and PCOS, but it was not remarkable (P = 0.068). But, no statistically significant connection was seen between the use of LEU (Lucien), MET (methionine), CYS (cysteine), PHE (phenylalanine), VAL (valine), ASP (asparagines), GLU (glutamic acid), and PCOS. Although, there was significant relationship between glycine, prolin, and methionine with PCOS. Conclusions: According to the results of this study, significant relationship was observed between glycine, prolin, and methionine and BCAA/AAA ratio with PCOS. [ABSTRACT FROM AUTHOR]

Esophageal squamous cell carcinoma (ESCC) is an aggressive tumor that is typically diagnosed only when the tumor has gained remarkable size, extended to peripheral tissues, and led to dysphagia. Five-year survival of advanced cancer is still very poor (19%), even with improved surgical techniques and adjuvant chemoradiation therapy. Therefore, early detection and prevention are the most important strategies to reduce the burden of ESCC. Our review will focus on the studies conducted in Golestan province, an area with a high prevalence of ESCC in northern Iran. We review three aspects of the research literature on ESCC: epidemiological features, environmental factors (including substance abuse, environmental contaminants, dietary factors, and human papilloma virus [HPV]), and molecular factors (including oncogenes, tumor suppressor genes, cell cycle regulatory proteins, and other relevant biomarkers). Epidemiological and experimental data suggest that some chemicals and lifestyle factors, including polycyclic aromatic hydrocarbons (PAHs), cigarette smoking, opium use, and hot tea drinking are associated with the development of ESCC in Golestan. HPV infects the esophageal epithelium, but so far, no firm evidence of its involvement in esophageal carcinogenesis has been provided. Some of these factors, notably hot tea drinking, may render the esophageal mucosa more susceptible to injury by other carcinogens. There are few studies at molecular level on ESCC in Golestan. Increasing awareness about the known risk factors of ESCC could potentially reduce the burden of ESCC in the region. Further studies on risk factors, identifying high risk populations, and early detection are needed. [ABSTRACT FROM AUTHOR]

Increase in cases of various cancers has encouraged the researchers to discover novel, more effective drugs from plant sources. This study is a review of medicinal plants in Iran with already investigated anticancer effects on various cell lines. Thirty-six medicinal plants alongside their products with anticancer effects as well as the most important plant compounds responsible for the plants’ anticancer effect were introduced. Phenolic and alkaloid compounds were demonstrated to have anticancer effects on various cancers in most studies. The plants and their active compounds exerted anticancer effects by removing free radicals and antioxidant effects, cell cycle arrest, induction of apoptosis, and inhibition of angiogenesis. The investigated plants in Iran contain the compounds that are able to contribute effectively to fighting cancer cells. Therefore, the extract and active compounds of the medicinal plants introduced in this review article could open a way to conduct clinical trials on cancer and greatly help researchers and pharmacists develop new anticancer drugs. [ABSTRACT FROM AUTHOR]

Background: Chronic myelogenous leukemia (CML) is a kind of hematopoietic stem-cell cancer. A significant number of CML patients who do not achieve an acceptable response to therapy, show acquired resistance against Imatinib. One of the most considerable causes of resistance against Imatinib as the first line of therapy, are BCR-ABL kinase domain mutations. Objectives: One of the most considerable causes of resistance against Imatinib as the first line of therapy, are BCR-ABL kinase domain mutations. Patients and Methods: The study was performed on 39 CML patients with Imatinib resistance. Basic hematologic parameters in blood samples were checked to identify hematologic response. To identify molecular response, BCR-ABL/ABL ratio was assessed by Real-time PCR. The ABL kinase domain amplification was performed by PCR. Restriction fragment length polymorphism (RFLP) was performed to detect four common mutations (T315I, Y253H, E255K and M351T). Finally the results were approved by direct sequencing. Results: In this study, the Y253H mutation, detected by RFLP method and confirmed by direct sequencing, was the prevalent ABL kinase domain mutation in these 39 CML patients. The G250E, V379I and L384M mutations were found in three different cases with failure molecular response. CML patients with these four ABL kinase domain mutations cannot achieve major molecular response (MMR). In addition, complete hematologic response (CHR) was observed only in the V379I mutated case and not in other mutated patients. Conclusions: Identification of ABL kinase domain mutations may be used as a proper and useful method for improving therapeutic strategies, avoiding delay in treatment and excessive expenditure in CML patients with Imatinib resistance. [ABSTRACT FROM AUTHOR]

Improvement of insulin resistance and inflammation is a basic strategy in the management of type 2 diabetes. There is limited evidence that prebiotics improve insulin resistance and inflammation. However, the ameliorating effect of resistant dextrin, as a prebiotic, on insulin resistance and inflammation in patients with type 2 diabetes has not been investigated so far. Therefore, the present study aimed to examine the effects of resistant dextrin on insulin resistance and inflammation in type 2 diabetic patients. In a randomised controlled clinical trial, fifty-five women with type 2 diabetes were assigned to two groups: the intervention group (n 30) and the control group (n 25). The intervention group received a daily supplement of 10 g resistant dextrin and the control group received a similar amount of maltodextrin as placebo for 8 weeks. Fasting plasma glucose (FPG), HbA1c, insulin, high-sensitivity C-reactive protein (hs-CRP), IL-6, TNF-α, malondialdehyde (MDA) and serum endotoxin concentrations were measured before and after the intervention. Data were analysed using SPSS (version 13). Paired and unpaired t tests and ANCOVA were used to compare quantitative variables after the intervention. Patients supplemented with resistant dextrin exhibited a significant decrease in fasting insulin (20·1 pmol/l, 22·8 %), homeostasis model assessment of insulin resistance (1·3, 24·9 %), quantitative insulin sensitivity check index (0·2, 7·2 %), IL-6 (1·4 pg/ml, 28·4 %), TNF-α (5·4 pg/ml, 18·8 %), MDA (1·2 nmol/ml, 25·6 %) and endotoxin (6·2 endotoxin units/ml, 17·8 %) concentrations than those supplemented with maltodextrin (P< 0·05). Decreases in FPG (0·05 mmol/l, 0·6 %), HbA1c (0·5 %, 9·6 %) and hs-CRP (2·7 ng/ml, 35·1 %) concentrations in the resistant dextrin group were not significant when compared with the maltodextrin group. In conclusion, resistant dextrin supplementation can modulate inflammation and improve insulin resistance in women with type 2 diabetes. [ABSTRACT FROM PUBLISHER]

Background: Bacterial superantigen Staphylococcal Enterotoxins (SEs), has stimulated polyclonal T cells irrespective of their antigen specificity, resulted a massive release of cytokines, and suggested that they could be assigned as a candidate of new antitumor agents. Recent attempts have done to specifically target superantigens towards tumors, subsequently Monoclonal antibodies and tumor-related ligands have employed as targeting molecules of superantigen for the preclinical treatment of different tumors. Here, we have evaluated TGFαL3-SEB fusion protein as a new antitumor candidate by genetically fusing the third loop of transforming growth factor alpha (TGFαL3) to Staphylococcal Enterotoxin type B. Methods: An in silico techniques have launched to characterize the properties and structure of the protein, before initiating the experimental study, we have predicted physicochemical properties, structures, stability, MHC binding properties and ligand-receptor interaction of this chimeric protein by means of computational bioinformatics tools and servers. Results: Our results have indicated codon adaptation index of tgfαl3-seb fusion gene has increased from 0.5 in the wild type sequences to 0.85 in the chimeric optimized gene. The mfold data has shown the tgfαl3-seb mRNA was stable enough for efficient translation in the new host. Based on Ramachandran plot TGFαL3-SEB has classified as a stable fusion protein. Our result has shown fusing of TGFaL3 in N-terminal of the TGFαL3-SEB construct, had no effects on MHC binding and subsequently superantigenic activity of SEB. Finally based on ligand-receptor docking the binding ability of TGFaL3 was strong enough to its receptor, so TGFαL3-SEB could be assigned as a new antitumor candidate in cancer immunotherapy. Conclusion: Our results have proposed that TGFαL3-SEB was a stable fusion protein with proper affinity to its receptor that overexpressed in various human carcinomas, so it could generate potent immune response towards tumors. [ABSTRACT FROM AUTHOR]

Wild Syrian rue (Peganum harmala L. family Zygophyllaceae) is well-known in Iran and various parts of this plant including, its seeds, bark, and root have been used as folk medicine. Recent years of research has demonstrated different pharmacological and therapeutic effects of P. harmala and its active alkaloids, especially harmine and harmaline. Analytical studies on the chemical composition of the plant show that the most important constituents of this plant are beta-carboline alkaloids such as harmalol, harmaline, and harmine. Harmine is the most studied among these naturally occurring alkaloids. In addition to P. harmala (Syrian rue), these beta-carbolines are present in many other plants such as Banisteria caapi and are used for the treatment of different diseases. This article reviews the traditional uses and pharmacological effects of total extract and individual active alkaloids of P. harmala (Syrian rue). [ABSTRACT FROM AUTHOR]

Introduction: Gastric cancer remains the second most common cause of cancer-related deaths worldwide. In many malignancies like, lung and breast, multiple prognostic factors are known, such as mutations in Ki-67, HER-2/neu, p53. In this study, we evaluated immunohistochemical protein expression patterns of cell-cycle-regulators p53, proliferation marker Ki-67, surface expression of CD44, HER-2/neu oncogene proposed as useful prognostic factors. Methods: In this descriptive-analytic study, we evaluate 100 patients with gastric cancer who were referred to Shahid Ghazi Hospital or other oncology clinics of Tabriz University of Medical Sciences in 2005-2010. Patients with pathologic confirmation of gastric cancer were selected. Expression of p53, ki-67, CD-44, HER-2/neu were detected by immunohistochemical staining. Results: In this study, 100 patients with gastric cancer participated. 76(76%) were men and 24(24%) were women with mean age of 64.02(8.05) years. Seventy two samples were intestinal type and 28 were diffuse type. CD44 was positive in 27(27%) patients. P53 was positive in 35(35%) patients. Ki-67 was positive in 53(53%) patients. HER-2/neu was positive in 51(51%) patients. Conclusion: The frequency of positive p53, Ki-67, CD44 and HER-2/neu varied in different studies. Positive Ki-67 and HER-2/neu were not associated with changes in survival but positive p53 and CD44 were significantly associated with improved survival. [ABSTRACT FROM AUTHOR]

Background: MDM2, E-cadherin, survivin and Her2 genes are involved in the regulation of normal cell growth. However, any crucial change in their expression levels can convert a normal cell into a cancer cell. Numerous studies have identified alterations of these gene expression levels in various cancers, particularly in breast cancer. Thus, they may be used as diagnostic biomarkers. In this experiment, we aim to evaluate these gene transcripts in patients' peripheral blood and compare the results with healthy individuals. Methods: RNA was extracted from peripheral blood cells of 52 breast cancer patients and 52 healthy volunteers. Then, cDNA was synthesized and assessed for MDM2, E-cadherin, and survivin and Her2 gene transcriptions in peripheral blood samples by quantitative real-time polymerase chain reaction. Results: There were no considerable differences in the expression of MDM2, Ecadherin, survivin and Her2 in cancer patients compared to healthy individuals. However, there were significantly correlation between E-cadherin, survivin and Her2 expression and some of the clinicopathological characteristics of patients studied. Also, survivin transcripts expression was positively correlated with Her2, E-cadherin, and MDM2 gene expressions. Conclusion: These results indicated no variations in MDM2, E-cadherin, Her2 and survivin gene expressions in patients compared to controls. We might not consider the examined biomarkers as valuable prognosis factors in primary breast cancer. However, additional research should be undertaken to assess these four genes in a larger sample size. [ABSTRACT FROM AUTHOR]

Background: Imatinib mesylate is a drug used in treating chronic myeloid leukemia (CML). It induces apoptosis and inhibits cell proliferation. This study aimed to evaluate hematologic and molecular responses to Imatib (Cipla Limited, Mumbai, India) in 30 chronic phase CML patients. Methods: Physical examination, CBC test, and peripheral blood smear were performed in order to assess the hematologic response in patients. Molecular response was evaluated through quantitative assessment of BCR-ABL fusion gene expression by real-time reverse transcriptase polymerase chain reaction (RT-PCR). The correlation of molecular and hematologic responses with the patient's age and sex and also with dosage and duration of Imatib consumption was analyzed statistically. Results: Ninety percent of the patients showed some sort of hematologic response that had no significant correlation with a patient's age or sex, dosage, or duration of Imatib consumption (P>0.05). Overall, 46.7% of patients showed complete molecular response (CMR), 43.3% showed partial molecular response, and 10% showed no molecular response (NMR) to Imatib. A reverse significant correlation was noted between the type of molecular response and patient's age (P<0.05). In contrast, no significant correlation was found between the type of molecular response and patient's sex, dosage, or duration of Imatib consumption (P>0.05). Conclusion: Our study results indicate that molecular and hematologic responses to Imatib were acceptably good and therefore its efficacy is comparable to that of more expensive brands like Gleevec. [ABSTRACT FROM AUTHOR]

Background:Studies on the determination of carnitine levels and nutritional status in patients of type II diabetes.Objective:We designed this study to determine changes of serum-free L-carnitine in type II diabetic women.Design:A cross-sectional study (case–control study).Setting:Clinical of Endocrinology and Metabolism, Sina Hospital, Pharmacological Research Center, Tabriz Medical university, Iran.Patients and methods:Taking into account the importance of the control of diabetes, in the present case-control study, the levels of serum-free L-carnitine, blood glucose and lipids, systolic and diastolic blood pressure, body mass index (BMI) and nutritional status assessed in the case and control groups which were selected by the simple sampling method. The control group (n=18) included patients with no complications and the case group (n=33) was grouped into three subgroups including patients with retinopathy, hyperlipidemia and neuropathy.Results:Study results indicated that the mean serum-free L-carnitine concentration in the case group was significantly lower than its mean concentration level in the control group, 39.63±8.99 vs 53.42±0.93 μmol/l, respectively (P<0.001). Serum-free L-carnitine in retinopathy, hyperlipidemia and neuropathy case subgroups were 39.03±9.89, 39.63±8.99 and 40.44±12.50 μmol/l, respectively (P>0.05). No significant difference was found between the serum-free carnitine levels of the case subgroups. The mean blood glucose, triglycerides, total cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol levels and systolic and diastolic blood pressure were significantly higher in the case group than in the control group.Conclusion:In this study, the mean serum-free L-carnitine levels in diabetic patients with complications was almost 25% lower than in diabetic patients with no complications. On the basis of the study results, carnitine supplementation in diabetic patients, especially in patients with diabetes complications, might be useful.European Journal of Clinical Nutrition (2007) 61, 892–895; doi:10.1038/sj.ejcn.1602594; published online 21 February 2007 [ABSTRACT FROM AUTHOR]

Background: Glycogen storage disease (GSD) type IXb is one of the rare variants of GSDs. It is a genetically heterogeneous metabolic disorder due to deficient hepatic phosphorylase kinase activity. Diagnosis of GSD can be difficult because of overlapping manifestations. Mutation analysis of the genes related to each type of GSD is supposed to be problem-solving, however, the presence of novel mutations can be confusing. In this case report, we will describe our experience with a young girl with the diagnosis of GSD and two novel mutations related to GSD type IXb., Case Presentation: A 3-year- old girl presented with short stature, hepatomegaly, and liver cirrhosis. No specific diagnosis was made based on laboratory data, so liver biopsy and targeted-gene sequencing (TGS) were performed to find out the specific molecular basis of her disease. It was confirmed that the patient carries two novel variants in the PHKB gene. The variant in the PHKB gene was classified as pathogenic., Conclusions: This is the first reported case of a dual molecular mutation of glycogen storage disease type IXb in the same patient. Two novel variants in PHKB were identified and one of them was a pathogenic split-site mutation. In conclusion, for the first time, identification of the novel variants in this patient expands the molecular and the phenotype basis of dual variants in GSD-IXb.