Correlation of IDH1 gene expression error in breast tumor biopsy in patients with invasive ductal carcinoma.

One of the most important cancers in terms of worldwide prevalence is breast tumors, which have been less investigated in correlation with the enzyme Isocitrate Dehydrogenase 1 (IDH1) gene. The aim of this study was that expression of this gene could have significant effects on the progression of metastasis and invasive disease in breast cancer patients. We used the molecular method of RT-PCR with SYBR-Green to analyze breast tumor tissue from patients with metastasis and non-metastasis, the latter confirmed by the pathology department of Shohada-e Tajrish Hospital (serving as a control group). Also, patients population and its relationship with the degree of tumor in the IDH1 gene was investigated. The IDH1 gene has shown high expression in patients with metastatic breast cancer rather than in patients with non-metastatic breast cancer. The metastatic samples were compared with non-metastatic samples for IDH1 mRNA expression. In this research work, 72.5% (29 samples) were up-regulated in comparison to 27.5% of samples (11 samples) that did not exhibit high expression (P=0.000).  This study examined the IDH1 gene expression, suggesting that changes in this gene's expression could impact the prognosis of breast cancer. However, further research is needed to draw definitive conclusions.

Clinical and genetic characterization of neuronal ceroid lipofuscinoses (NCLs) in 29 Iranian patients: identification of 11 novel mutations.

Neuronal ceroid lipofuscinoses (NCLs) are neurodegenerative lysosomal storage diseases which are considered among the most frequent causes of dementia in childhood worldwide This study aimed to identify the gene variants, molecular etiologies, and clinical features in 23 unrelated Iranian families with NCL. In total, 29 patients with neuronal ceroid lipofuscinoses (NCLs), diagnosed based on clinical manifestations, MRI neuroimaging, and electroencephalography (EEG), were recruited for this study. Through whole-exome sequencing (WES), functional prediction, Sanger sequencing, and segregation analysis, we found that 12 patients (41.3%) with mutations in the CLN6 gene, 7 patients (24%) with the TPP1 (CLN2) gene variants, and 4 patients (13.7%) with mutations in the MFSD8 (CLN7) gene. Also, mutations in each of the CLN3 and CLN5 genes were detected in 2 cases and mutations of each PPT1 (CLN1) and CLN8 gene were observed in only 1 separate patient. We identified 18 different mutations, 11 (61%) of which are novel, never have been reported before, and the others have been previously described. The gene variants identified in this study expand the number of published clinical cases and the variant frequency spectrum of the neuronal ceroid lipofuscinoses (NCLs) genes; moreover, the identification of these variants supplies foundational clues for future NCL diagnosis and therapy.

Microbiome modulation in inflammatory diseases: Progress to microbiome genetic engineering.

Recent developments in sequencing technology and analytical approaches have allowed researchers to show that the healthy gut microbiome is very varied and capable of performing a wide range of tasks. The importance of gut microbiota in controlling immunological, neurological, and endocrine function is becoming well-recognized. Thereby, numerous inflammatory diseases, including those that impact the gastrointestinal system, as well as less obvious ones, including Rheumatoid arthritis (RA), cancer, gestational diabetes (GD), type 1 diabetes (T1D), and type 2 diabetes (T2D), have been linked to dysbiotic gut microbiota. Microbiome engineering is a rapidly evolving frontier for solutions to improve human health. Microbiome engineering seeks to improve the function of an ecosystem by manipulating the composition of microbes. Thereby, generating potential therapies against metabolic, inflammatory, and immunological diseases will be possible through microbiome engineering. This essay first provides an overview of the traditional technological instruments that might be used for microbiome engineering, such as Fecal Microbiota Transplantation (FMT), prebiotics, and probiotics. Moreover, we will also discuss experimental genetic methods such as Metagenomic Alteration of Gut microbiome by In situ Conjugation (MAGIC), Bacteriophage, and Conjugative plasmids in manipulating intestinal microbiota.

Bcl-2 expression in cell lines breast cancer and death program.

Breast cancer is a hormone-dependence and heterogenic disease. Drug resistance is the main reason for the failure of breast cancer treatment. Combinatory medications are methods for treatment but they are not sufficient in action. However, new approaches like molecular therapy reveal a new insight into cancer treatment. Studies show that Bcl-2 gene family inhibitors and ER blockers cause the improvement of recovery. Interfering molecules such as antisense ones can inhibit the expression of Bcl-2 and push the cancer cells to apoptosis. Our team designed a new Antisense Oligonucleotide (ASO) based on Antisense oligo G3139. MCF-7 and MDA-MB-231 cell lines were used to evaluate cellular proliferation. Liposomes and cationic nano-complex (Niosome) are used to increase the cellular delivery of ASO and Tamoxifen. We also investigated the cytotoxicity and apoptotic effects of Tamoxifen, naked ASO and Nano-packed ASO. The results indicated significant down-regulation of the Bcl-2 gene and inhibition of MCF-7 and MDA-MB-231 cellular proliferation. Flow-cytometry showed early apoptosis in all cell groups. The newly designed ASO reduced the expression of the Bcl-2 gene. It also had a synergistic effect with the Tamoxifen. The cationic nano-complex (Niosome) was more efficient than the liposome in delivering designed oligo antisense Bcl-2 in the cancer cells.

Evaluation of the current MicroRNAs expression levels as potential biomarkers in Oral Squamous Cell Carcinoma.

As the most common malignancy, oral squamous cell carcinoma (OSCC) is typically fatal. The survival of patients with oral cancer has not improved, and tumor recurrence remains high. During tumorigenesis, microRNAs (miRNAs) regulate gene expression. Patients' life expectancy can be determined by prognostic survival biomarkers, which can focus therapy on specific targets. This study evaluated five miRNAs associated with OSCC for their prognostic impact. It was determined through microarray analysis and quantitative reverse transcription polymerase chain reaction that there was a significant difference in the expression of miRNAs between OSCC patients and control patients in plasma. We used the unpaired t-tests and the Mann-Whitney test to conduct the statistical analysis. Based on the study's results, five miRNAs have been found to have significantly different expression levels in the plasma of patients with OSCC; in particular, miR-31 was found to have a significantly higher expression level in OSCC patients' plasma as compared with healthy controls. Aside from that, there was a significant reduction in the expression of miR-100, miR-199a, miR-203, and mir345 in the plasma of OSCC patients (P < 0.05). To better understand the importance of miRNAs in OSCC, various OSCC cases were analyzed. Detecting miRNAs in plasma may be a useful diagnostic tool for oral squamous cell carcinoma.

Evaluation of Hepatoprotective and Gastroprotective Activities of Paspalidium flavidum Leaves Extract in Experimental Animal Models.

Paspalidium flavidum (watercrown grass), a medicinal plant, is traditionally used in liver ailments and stomach problems. The hepatoprotective and gastroprotective activities of the aqueous methanol extract of Paspalidium flavidum (AMEPF) were studied in experimental animal models. Paracetamol and aspirin were used to induce hepatotoxicity and gastric ulcer in rats, respectively. Biochemical hepatic parameters, gastric pH, total acidity, ulcer index, percentage protection, nitric oxide and TNF-α were measured in AMEPF-treated groups. Moreover, GC-MS analysis of AMEPF was performed. Pretreatment with AMEPF improved the blood lipid profile and restored liver function tests in paracetamol-induced hepatotoxicity. While in aspirin-induced gastric ulcer, oral administration of AMEPF significantly reduced (P<0.05) the gastric lesions, total acidity and ulcer scoring index, TNF-α with upregulation of nitric oxide when compared with the Diseased group. AMEPF exhibited anti-lipid peroxidation activity. Histopathological studies were in good agreement with the biochemical findings. GC-MS analysis revealed the presence of anti-oxidant phyto-constituents, including oleic acid and 1,2-benzenedicarboxylic acid, mono(2-ethylhexyl) in AMEPF. This study suggested that aqueous methanol extract from the leaves of P. flavidum has beneficial hepatoprotective and gastroprotective activities related to its anti-oxidant phytochemicals.

Diagnostic of Cytokeratin-19 Gene Expression in Iranian Breast Cancer Patients.

Sentinel lymph node (SLN) biopsy is currently the recommended procedure for axillary staging in clinically node-negative early breast cancer at diagnosis. The present study aimed to identify Cytokeratin-19 (CK19) gene profiles that accurately predicted the outcome of breast cancer patients. Fifty tumor samples from breast cancer patients were analyzed for the expression of the CK19 gene using quantitative PCR. Also, normal breast tissues (N = 50) were taken from the same patients that had undergone partial or total mastectomy. This gene signature was confirmed based on tumor's stage, grade, and estrogen receptor (ER) status, using conditional logistic regression. Based on these findings, the negative reported lymph nodes for metastasis had micrometastasis in significant values. There was a significant difference between normal and cancer samples in  CK19 expression. In this sentinel node evaluation, the relationship of this gene with tumor characteristics needs to be established and discussed finding a clear role for this gene in tumor outcome.

Characterizing Iranian Pediatric Patients With Relapsed Acute Lymphoblastic Leukemia Through Gene Expression Profiling of Common ATP Binding Cassette Transporters Subfamily C.

BACKGROUND: The correlation between gene expression of ABCC transporters and recurrence as a treatment failure in pediatric patients with acute lymphoblastic leukemia (ALL) is an unsolved problem in scientific associations. The aim of this study was to evaluate the predictive value of ABCC1-6 gene expression pattern for estimating recurrence in Iranian pediatric patients with ALL. MATERIALS AND METHODS: Iranian pediatric patients with approved ALL enrolled in this study as 2 groups of case (relapsed ALL) and control (treated individuals who lasted for >3 years following their final treatment). Real-time polymerase chain reaction was done with GAPDH for expressing ABCC1-6 transporter genes. Cumulative doses of Vincristine, Daunorubicin, and L-Asparginase were checked for each patient. Gathered data analyzed with SPSS version 22 and REST 2009 software. RESULTS: Thirty-nine samples as 23 relapsed ALL and 16 controls enrolled. High expression of ABCC2-6 and low expression of ABCC1 were detected in pediatric patients with relapse. ABCC3 and ABCC4 had significant relation with high-risk patients of NCI group. Also, ABCC4 and ABCC6 had more expression with high doses of Daunorubicin and L-Asparginase. CONCLUSIONS: Designed expression pattern have the predictive value for estimating of conferring relapse in Iranian pediatric patients with diagnosed ALL. The authors suggest of designing a multiple childhood malignancy center project to evaluate this pattern in a cohort study.

ATP-Binding Cassette transporters' gene expression in pediatric patients with acute leukemia; a comprehensive analysis of published reports through PubMed search engine.

Multidrug resistance based on ABC transporters' gene expression is one of the most important health challenges through chemotherapy of patients. This resistance can cause relapse or treatment failure. The goal of this conducted study was to evaluate the results of published reports which considered ABC transporters' gene expression in pediatric patients with acute leukemia. PubMed as a free search engine was chosen. The following Mesh terms were used as: "ATP-binding cassette transporters" OR "ABC-transporters*" AND "gene expression*" AND "leukemia" OR "ALL" OR "AML" OR "acute leukemia*". Age was set as an additional filter with the age range of birth to 18 years old. Initial screening was performed according to inclusion and exclusion criteria and the quality of the selected papers was assessed. Papers categorized into three sections as: pediatric patients with ALL (6 papers from 1998-2015); pediatric patients with AML (3 papers from 1992-2011) and pediatric patients with ALL and AML (7 papers from 1992-2014). Totally 1118 patients enrolled in the searched studies (ALL and AML: 488; ALL: 405; AML: 225). The common method for evaluating gene expression of ABC transporters was RT-PCR. More than 50% of the papers showed the influence of ABC transporters' gene expression on prognosis and treatment failures of patients. Despite controversial results, the gathered information in the current report serves as a comprehensive referential resource, which can be beneficial for future planning around this title, especially in developing countries.

The roles of DNA epigenetics and clinical significance in Chronic Myeloid Leukemia: a review.

Chronic Myeloid Leukemia (CML) is a myeloproliferative disorder characterized by the genetic translocation t(9;22) (q34;q11.2) encoding for the BCR-ABL fusion oncogene. Growing body of evidence suggests that epigenetic abnormalities are involved in tyrosine kinase resistance in CML, leading to leukemic clone escape and disease propagation. The significant of therapeutic role in chronic myeloid leukemia (CML) depends on both genetic and epigenetic mechanisms.  This article focused on the CML and epigenetic and clinical significance. An electronic search of peer-reviewed articles was systematically performed to obtain the relevant literature with the CINAHL, cancer, Google scholar, self-experience and PubMed databases. The keywords included leukemia, cancer, illness, epigenetic. The inclusion criteria for the reviews were that the documents were original quantitative research and published in English. Articles that were not directly relevant to the present objective were excluded. Current progress in molecular biology and bioinformatics offer novel promising experiments namely as next generation sequencing for new development in epigenetic figures characterization and more understanding of the epigenetic mechanisms to be successfully utilized for personalized CML therapy in the next coming years.

Detection of gene expression in sentinel lymph node of primary breast cancer patients.

Sentinel lymph node (SLN) micrometstasis detection improves outcome for breast cancer follow up procedure. The aim of the present study was to identify gene profiles that accurately predicted the outcome of breast cancer patients. Fifty tumor sample from breast cancer patients were analyzed for the expression of 3 genes using quantitative-PCR. Also clinical verification for recurrence to distant organs was performed. Three gene signature were confirmed based on tumor's stage, grade, ER status, using conditional logistic regression. Based on this findings, the negative reported lymph nodes for metastasis, had micro metastasis in significant values. There was a significant difference between normal and cancer samples in 3 gene expression marker and also there was meaningful relationship between three gene expression with tumor's grade, stage according to progression of tumor. A novel gene expression signature predictive of micro metastatic patients was evaluated. In this assessment, relationship between this gene with tumor's features   that finding clear role for these genes with tumor's outcome, needs to be established.

Determinants of survival of common childhood cancers in Iran.

BACKGROUND: Cancer is the second most common cause of morbidity and mortality in children. This study aimed to epidemiologically and demographically assess common cancers in children in Iran. MATERIALS AND METHODS: This cohort study was conducted on children registered in Mahak Hospital and Rehabilitation Complex (which is a non-governmental organizations (NGO)-related hospital for only malignant diseases). A total of 2232 questionnaires were filled out for cancer patients between 2007 and 2016. The factors including age, gender, race, family history, type of treatment, and type of cancer were entered into Cox regression model to examine their effect on mortality of children diagnosed with cancer. RESULTS: The Cox regression model showed that age, race, type of cancer, family history of cancer, and type of treatment had a significant effect on mortality of children diagnosed with cancer (P < 0.05). The hazard ratio (HR) of mortality in 10-15 years old was higher than that of 1-5 years old (P = 0.03, HR = 1.3). The HR of mortality in patients with brain tumor (P < 0.01, HR = 2.24), sarcoma (P < 0.01, HR = 2.32), and neuroblastoma (P < 0.01, HR = 2.56) was twice the value in patients with leukemia. The HR of mortality in patients who had a family history of cancer was higher than that of patients without it (P < 0.01, HR = 1.33). Patients who had undergone chemotherapy along with surgery and radiotherapy (P = 0.02, HR = 0.68) and patients who received chemotherapy along with surgery (P = 0.01, HR = 0.67) had a lower HR of mortality compared to the chemotherapy group. CONCLUSION: Young age, multidisciplinary approach, and absence of family history were associated with lower hazard of death in children diagnosed with cancer; brain tumor, leukemia, and sarcoma had higher hazard of mortality compared to leukemia. Children with a family history of cancer should be under regular follow-up. Treatment should be multidisciplinary and comprehensive.

Expression analysis of four long noncoding RNAs in breast cancer.

Breast cancer is a molecularly heterogeneous disease which necessitates a search for markers to provide a more specific classification of this disorder. Long noncoding RNAs as the important subset of noncoding transcripts have been shown to be involved in tumorigenic processes. So, they may be used as markers for early detection of cancer and evaluation of cancer prognosis. In addition, they can be applied as therapeutic targets. In this study, we analyzed expression of four long noncoding RNAs (lncRNAs) namely SOX2OT, PTPRG-AS1, ANRASSF1, and ANRIL in 38 breast cancer tissues and their adjacent noncancerous tissues (ANCTs). ANRASSF1 expression was not detected in any noncancerous tissue. All lncRNAs showed significant overexpression in tumor tissues compared with ANCTs. No association was found between gene expressions and individual clinical data such as tumor stage, grade, size and hormone receptor status except for ANRASSF1 expression and Her2/neu status. In addition, ANRASSF1 and ANRIL expressions were significantly higher in triple negative samples. This study suggests a putative role for these lncRNAs in breast cancer and implies that they can be used as potential cancer biomarkers.

A genetic variant in CAMKK2 gene is possibly associated with increased risk of bipolar disorder.

A recent large-scale study have reported that rs1063843, a single nucleotide polymorphism located in the CAMKK2 gene is highly associated with schizophrenia in European and Han Chinese populations. Increasing evidences show that schizophrenia and bipolar disorder have some common genetic variance. Here, we evaluated the association of this variant with schizophrenia and bipolar disorder in Iranian population. Genomic DNA was extracted from peripheral blood of 500 schizophrenic patients, 500 bipolar patients and 500 normal controls and all were genotyped for the rs1063843 using a PCR-RFLP method. The allele frequency of rs1063843 was significantly different in both schizophrenia and bipolar patients comparing to control group. For the first time, we showed that rs1063843 is highly associated with bipolar disorder, although more replication studies are needed to confirm our findings. Our results also support the findings of previous studies suggesting a significant association between rs1063843 and schizophrenia.

A Bioinformatics Approach to the Identification of Variants Associated with Type 1 and Type 2 Diabetes Mellitus that Reside in Functionally Validated miRNAs Binding Sites.

The present work is aimed at finding variants associated with Type 1 and Type 2 diabetes mellitus (DM) that reside in functionally validated miRNAs binding sites and that can have a functional role in determining diabetes and related pathologies. Using bioinformatics analyses we obtained a database of validated polymorphic miRNA binding sites which has been intersected with genes related to DM or to variants associated and/or in linkage disequilibrium (LD) with it and is reported in genome-wide association studies (GWAS). The workflow we followed allowed us to find variants associated with DM that also reside in functional miRNA binding sites. These data have been demonstrated to have a functional role by impairing the functions of genes implicated in biological processes linked to DM. In conclusion, our work emphasized the importance of SNPs located in miRNA binding sites. The results discussed in this work may constitute the basis of further works aimed at finding functional candidates and variants affecting protein structure and function, transcription factor binding sites, and non-coding epigenetic variants, contributing to widen the knowledge about the pathogenesis of this important disease.

Bioinformatics prioritization of SNPs perturbing microRNA regulation of hematological malignancy-implicated genes.

The contribution of microRNAs (miRNAs) to cancer has been extensively investigated and it became obvious that a strict regulation of miRNA-mRNA regulatory network is crucial for safeguarding cell health. Apart from the direct impact of miRNA dysregulation in cancer pathogenesis, genetic variations in miRNAs are likely to disrupt miRNA-target interaction. Indeed, many evidences suggested that SNPs within miRNA regulome are associated with the development of different hematological malignancies. However, a full catalog of SNPs within miRNAs target sites of genes relevant to hematopoiesis and hematological malignancies is still lacking. Accordingly, we aimed to systematically identify and characterize such SNPs and provide a prioritized list of most potentially disrupting SNPs. Although in the present study we did not address the functional significance of these potential disturbing variants, we believe that our compiled results will be valuable for researchers interested in determining the role of target-SNPs in the development of hematological malignancies.

Application of multiplex PCR for Rapid and sensitive detection of human papillomaviruses in cervical cancer.

OBJECTIVES: Reffering to an increase in cervical cancer in the recent years, rapid, sensitive and economical detection of human papillomaviruses (HPVs) as causative agents of cervical cancer is important. The traditional methods for the detection of HPVs in cervical cancer, such as pap smear, suffer from limitation and PCR has a potential to overcome the limitaitons. The purpose of present research work was to identify the five important strains of HPV (16, 18, 31, 33 and 45) simultaneously by Multiplex PCR application. METHODS: Study was done on 100 cervical lesions of women. DNA was extracted from specimens by a genomic DNA purification kit. A 5-plex PCR was developed for the simultaneous detection of major HPV. Five pair of new primers was designed for detection of HPV 16, 18, 31, 33 and 45 by Multiplex PCR. RESULTS: Among the 100 evaluated samples, 82 were found positive to HPVs. In the meantime the highest rate of infection was for HPV 16. Also 30 of HPV positive samples had infections with two or more HPV types. CONCLUSION: Multiplex PCR assay used in present study can provide a rapid, sensitive and economical method for detection of viral infections and is applicable to small volumes of vaginal samples.

Analysis of dystrophin gene in Iranian Duchenne and Becker muscular dystrophies patients and identification of a novel mutation.

Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are the most frequent muscular dystrophies. Present study aimed to determine the frequency of dystrophin gene alterations in Iranian DMD/BMD patients using molecular techniques. 146 Iranian DMD/BMD patients have been analyzed using two devised sets of multiplex polymerase chain reaction (M-PCR) followed by multiple ligation-dependent probe amplification (MLPA). Two isolated DMD and BMD patients were analyzed by DNA sequencing. 30.9 % of patients had single-exon deletion while group and contiguous exon deletions were identified in 41 % of the patients. The most numerous exon deletions included exons 45-50 and were identified in the first M-PCR set. Deletion detection rate was 99 % in first M-PCR set and remaining deletions (1 %) were identified in the second M-PCR set. MLPA analysis showed that there were two exons 3-5 and 41-43 duplications (1.4 %) in a BMD and a DMD patient, respectively. Two nonsense mutations including c.633dupA and c.6283 C>T were, respectively, found in a DMD and BMD patient in which c.633dupA has not ever been reported in DMD mutation database and was pathogenic mutation. Besides the report of frequency of dystrophin gene alteration in a subset of Iranian DMD/BMD patients, it was revealed that the proposed M-PCR protocol can be useful in the initial step of molecular diagnosis of DMD/BMD. Exon sequencing would be the final step in determining the mutation status of DMD/BMD patients following MLPA.

Association analysis of DISC1 gene polymorphisms with Attention-Deficit Hyperactivity Disorder in Iranian population.

BACKGROUND & OBJECTIVES: Attention deficit hyperactivity disorder (ADHD) is a common heritable psychiatric disorder with a worldwide prevalence of 5%. The etiology of ADHD is still incompletely understood, but several studies, consistently indicate the strong role of genetic factors on this disorder. The aim of this study was to determine the effect of three SNPs rs11122319, rs11122330 and rs6675281 in the etiology of ADHD in an Iranian children. METHODS: In this research work, for the first time, we investigated the association of three SNPs (rs11122330, rs6675281 and rs11122319) in the DISC1 gene with ADHD in Iranian population. Two hundred fourthy subjects composed of 120 patients and 120 healthy controls were included and tetra-primer ARMS PCR technique was used for genotyping all selected SNPs. RESULTS: We found differences in genotype and allele distributions of rs 6675281 polymorphism between our patients and controls. The A, T and A alleles were the more frequent alleles in rs11122319, rs6675281 and rs11122330 polymorphisms in both case and control groups respectively. The TT genotype was more frequent in control group compared to patients. (P value = 0.008, OR= 1.5837, 95% CI= 1.1012 to 2.2776). CONCLUSION: Our findings strengthens the role of DISC1 gene as a susceptibility locus for ADHD and indicate that rs6675281 polymorphism is a susceptibility factor for ADHD for the first time in children reported in an Iranian population in this part of the world.

Oncolytic viruses in lung cancer treatment: a review article.

Lung cancer has a high morbidity rate worldwide due to its resistance to therapy. So new treatment options are needed to improve the outcomes of lung cancer treatment. This study aimed to evaluate the effectiveness of oncolytic viruses (OVs) as a new type of cancer treatment. In this study, 158 articles from PubMed and Scopus from 1994 to 2022 were reviewed on the effectiveness of OVs in the treatment of lung cancer. The oncolytic properties of eight categories of OVs and their interactions with treatment options were investigated. OVs can be applied as a promising immunotherapy option, as they are reproduced selectively in different types of cancer cells, cause tumor cell lysis and trigger efficient immune responses.

A lot of research has been done to find a cure for lung cancer. Among the methods investigated is the treatment of cancer using a type of virus called an oncolytic virus (OV). Since tumors have unique properties, OVs tend to bind to them and activate immune cells to kill them. This article reviews the combination of OVs with other common cancer treatments which improves their effectiveness, causes fewer reactions and brings better results.