15 results on '"Kerachian MA"'
Search Results
2. Identification of long non-coding RNA using single nucleotide epimutation analysis: a novel gene discovery approach.
- Author
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Kerachian MA and Azghandi M
- Abstract
Background: Long non-coding RNAs (lncRNAs) are involved in a variety of mechanisms related to tumorigenesis by functioning as oncogenes or tumor-suppressors or even harboring oncogenic and tumor-suppressing effects; representing a new class of cancer biomarkers and therapeutic targets. It is predicted that more than 35,000 ncRNA especially lncRNA are positioned at the intergenic regions of the human genome. Emerging research indicates that one of the key pathways controlling lncRNA expression and tissue specificity is epigenetic regulation., Methods: In the current article, a novel approach for lncRNA discovery based on the intergenic position of most lncRNAs and a single CpG site methylation level representing epigenetic characteristics has been suggested., Results: Using this method, a novel antisense lncRNA named LINC02892 presenting three transcripts without the capacity of coding a protein was found exhibiting nuclear, cytoplasmic, and exosome distributions., Conclusion: The current discovery strategy could be applied to identify novel non-coding RNAs influenced by methylation aberrations., (© 2022. The Author(s).)
- Published
- 2022
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3. Long non-coding RNA AC087388.1 as a novel biomarker in colorectal cancer.
- Author
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Poursheikhani A, Abbaszadegan MR, and Kerachian MA
- Subjects
- Apoptosis genetics, Carcinogenesis genetics, Cell Cycle genetics, Cell Proliferation genetics, Down-Regulation, HT29 Cells, Humans, Wnt Signaling Pathway genetics, Biomarkers, Tumor genetics, Colorectal Neoplasms genetics, RNA, Long Noncoding genetics
- Abstract
Background: Several investigations have reported diverse roles of long non-coding RNA (lncRNA) in biological processes, tumor development, and progression of colorectal cancer (CRC). In this study, we investigated the lncRNA AC087388.1 tumorigenic role in CRC cells., Methods: The CRC tissues were collected at the Reza Radiotherapy and Oncology Center, Mashhad, Iran. The human SW-48 and HT-29 CRC cell lines were obtained from the national cell bank of Iran. The cells were cultured according to ATCC (the American Type Culture Collection) recommendations. Quantitative real-time PCR was applied to assess the RNA expression. ShRNA transfection was done to downregulate the target gene. MTT and apoptosis assays were conducted to evaluate cell proliferation and viability, respectively. Colony formation assay, wound healing assay, and invasion assay were applied to determine growth, motility, and invasion of the cells, respectively. ENCORI online tool was used as downstream enrichment analysis., Results: Forty CRC patients were encompassed in this study. The results demonstrated that the lncRNA SLC16A1-AS1, AC087388.1, and ELFN1-AS1 were significantly overexpressed in the CRC tissues in comparison to their normal counterpart margins. All the lncRNAs have shown significant Area Under Curve (AUC) values in the patients. Downregulation of lncRNA AC087388.1 remarkably decreased the cell proliferation and viability of the CRC cells. In addition, the data demonstrated that the downregulation of lncRNA AC087388.1 significantly suppressed cell growth and colony formation capability in the cells. Also, downregulation of lncRNA AC087388.1 attenuated motility and invasion of CRC cells, and significantly decreased the expression of invasion genes. In-silico functional enrichment analysis indicated that the lncRNA AC087388.1 has contributed to crucial signaling pathways in tumorigenesis such as the p53 and Wnt signaling pathways, apoptosis, and cell cycle., Conclusions: Altogether, we showed that lncRNA AC087388.1 has an oncogenic role in tumorigenesis of CRC, and it can be considered as a novel diagnostic and prognostic biomarker in CRC., (© 2022. The Author(s).)
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- 2022
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4. Association of SMAD7 genetic markers and haplotypes with colorectal cancer risk.
- Author
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Alidoust M, Hamzehzadeh L, Khorshid Shamshiri A, Afzaljavan F, Kerachian MA, Fanipakdel A, Aledavood SA, Allahyari A, Bari A, Moosanen Mozaffari H, Goshayeshi L, and Pasdar A
- Subjects
- Case-Control Studies, Genetic Markers, Genetic Predisposition to Disease, Genotype, Haplotypes, Humans, Polymorphism, Single Nucleotide, Risk Factors, Smad7 Protein genetics, Smad7 Protein metabolism, Colorectal Neoplasms epidemiology, Colorectal Neoplasms genetics
- Abstract
Purpose: Colorectal cancer (CRC) is one of the common cancers with a high mortality rate worldwide. In Iran, there has been a trend of increased incidence of colorectal cancer in the last three decades that necessitates the early diagnosis. Genetic factors have an influential role in its etiology along with the conventional risk factors such as age, diet, and lifestyle. Results from GWAS have shown significant associations between SMAD7 gene variants and risk of CRC. This study aimed to assess the association of certain polymorphisms as well as haplotypes of this gene and risk of colorectal cancer., Methods and Materials: This study was designed as a case-control association study. After obtaining ethical approval and informed consent, blood samples from 209 patients with colorectal cancer were collected and DNA was extracted. Four variants: rs4939827, rs34007497, rs8085824 and rs8088297 were genotyped using ARMS-PCR method., Results: SMAD7 rs4939827 in the recessive and co-dominant models was associated with colorectal cancer risk [TT/CT + CC: OR = 2.90, 95%CI (1.38-6.09), p = 0.005; CC + TT/CT: OR = 1.66, 95%CI (1.00-2.75), p = 0.01]. Haplotype analysis indicated that some SNP combinations including two for-SNPs haplotypes of T-T-C-C and T-C-C-A were significantly associated with CRC risk., Conclusion: Based on the identified association of SMAD7 gene variations and haplotypes with colorectal cancer risk in our population, genetic variations in this gene region may have a role in CRC development. This data may shed light on the genetic predisposition of CRC which involves different pathways including TGF-β., (© 2022. The Author(s).)
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- 2022
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5. Association of MTHFR C677T variant genotype with serum folate and Vit B12 in Iranian patients with colorectal cancer or adenomatous polyps.
- Author
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Ghorbani M, Azghandi M, Khayami R, Baharara J, and Kerachian MA
- Subjects
- Case-Control Studies, Female, Humans, Iran, Male, Middle Aged, Polymorphism, Genetic, Adenomatous Polyps genetics, Colorectal Neoplasms genetics, Folic Acid blood, Genotype, Methylenetetrahydrofolate Reductase (NADPH2) genetics, Vitamin B 12 blood
- Abstract
Background: The incidence of colorectal cancer (CRC) has increased during recent years in Iran and other developing countries. Clinical studies suggest that essential folate dietary intake and moderate deficiency of methylenetetrahydrofolate reductase (MTHFR) may protect and reduce the risk of CRC. The present study aimed to investigate the clinical significance of C677T polymorphism within the MTHFR gene and its correlation with the serum folate and Vit B
12 in the Iranian population suffering from CRC., Methods: Blood samples were taken from 1017 Iranian individuals (517 cases and 500 controls) who were referred for colonoscopy. TaqMan probe assay was performed for C677T MTHFR polymorphism. Sera were fractionated from the blood samples of 43 patients and controls and folate and Vit B12 concentrations were measured by a monobind kit. The correlation of MTHFR polymorphisms and folate/vitamin-B12 with CRC risk was analyzed., Results: In the current study, we found the frequency of three different genotypes of MTHFR polymorphism in the Iranian population i.e., CC, CT, and TT, to be 51.31, 26.73, 21.96 and 61, 32.2, 6.8 in case and control groups, respectively. The homozygote genotype of MTHFR rs1801133 polymorphism is associated with an increased risk of CRC by 3.68, 1.42, and 3.74-fold in codominant, dominant, and recessive models respectively (p value < 0.01). Our study revealed that there was no significant difference between the amount of folate and Vit B12 in the case and control groups (p value > 0.05)., Conclusions: This study revealed that there was no significant difference between the amount of folate and Vit B12 in the case and control groups. Furthermore, our results demonstrated a higher risk association for 677TT and 677TT + C677T genotypes of MTHFR compared with 677CC carriers among CRC patients., (© 2021. The Author(s).)- Published
- 2021
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6. Aberrantly methylated-differentially genes and pathways among Iranian patients with colorectal cancer.
- Author
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Ghorbani M, Azghandi M, and Kerachian MA
- Abstract
Background: Methylation plays an important role in colorectal cancer (CRC) pathogenesis. The goal of this study was to identify aberrantly differentially methylated genes (DMGs) and pathways through bioinformatics analysis among Iranian CRC patients using Methylation Next Generation Sequencing., Methods: This study has integrated results of SureSelectXT Methyl-Seq Target with the potential key candidate genes and pathways in CRC. Six CRC and six samples of normal colon were integrated and deeply analyzed. In addition to this gene methylation profiling, several other gene methylation profiling datasets were obtained from Gene Expression Omnibus (GEO) and TCGA datasets. DMGs were sorted and candidate genes and enrichment pathways were analyzed. DMGs-associated protein-protein interaction network (PPI) was constructed based on the STRING online database., Results: Totally, 320 genes were detected as common genes between our patients and selected GEO and TCGA datasets from the Agilent SureSelect analysis with selecting criteria of p-value < 0.05 and FC ≥ 1.5. DMGs were identified from hyper-DMGs PPI network complex and 10 KEGG pathways were identified. The most important modules were extracted from MCODE, as most of the corresponding genes were involved in cellular process and protein binding., Conclusions: Hub genes including WNT2, SFRP2, ZNF726 and BMP2 were suggested as potentially diagnostic and therapeutic targets for CRC.
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- 2021
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7. Detection of novel coronavirus (SARS-CoV-2) RNA in peripheral blood specimens.
- Author
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Azghandi M and Kerachian MA
- Subjects
- Betacoronavirus, COVID-19, COVID-19 Testing, Coronavirus Infections blood, Humans, Pandemics, Plasma virology, Pneumonia, Viral blood, SARS-CoV-2, Serum virology, Viral Load, Clinical Laboratory Techniques methods, Coronavirus Infections diagnosis, Pneumonia, Viral diagnosis, RNA, Viral blood
- Abstract
The latest outbreak of pneumonia caused by SARS-CoV-2 presents a significant challenge to global public health and has a major impact on clinical microbiology laboratories. In some situations, such as patients in coma condition, the oropharyngeal or nasopharyngeal sampling is seldom feasible, and blood sampling could be an alternative. In the current article, a comprehensive literature search has been conducted for detecting coronavirus disease 2019 (COVID-19) using plasma or serum samples. To date, twenty-six studies have used SARS-CoV-2 nucleic acid in plasma or serum (RNAaemia) to diagnose COVID-19. The pros and cons are discussed in this article. While the detection of SARS-CoV-2 viral load in respiratory specimens is commonly used to diagnose COVID-19, detecting SARS-CoV-2 RNA in plasma or serum should not lose sight and it could be considered as an alternative diagnostic approach.
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- 2020
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8. Identification of missense and synonymous variants in Iranian patients suffering from autosomal dominant polycystic kidney disease.
- Author
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Khadangi F, Torkamanzehi A, and Kerachian MA
- Subjects
- DNA Mutational Analysis, Exons, Humans, Iran, Sequence Analysis, DNA methods, Mutation, Missense, Polycystic Kidney, Autosomal Dominant genetics, Silent Mutation, TRPP Cation Channels genetics
- Abstract
Background: Autosomal dominant polycystic kidney disease (ADPKD), the predominant type of inherited kidney disorder, occurs due to PKD1 and PKD2 gene mutations. ADPKD diagnosis is made primarily by kidney imaging. However, molecular genetic analysis is required to confirm the diagnosis. It is critical to perform a molecular genetic analysis when the imaging diagnosis is uncertain, particularly in simplex cases (i.e. a single occurrence in a family), in people with remarkably mild symptoms, or in individuals with atypical presentations. The main aim of this study is to determine the frequency of PKD1 gene mutations in Iranian patients with ADPKD diagnosis., Methods: Genomic DNA was extracted from blood samples from 22 ADPKD patients, who were referred to the Qaem Hospital in Mashhad, Iran. By using appropriate primers, 16 end exons of PKD1 gene that are regional hotspots, were replicated with PCR. Then, PCR products were subjected to DNA directional Sanger sequencing., Results: The DNA sequencing in the patients has shown that exons 35, 36 and 37 were non- polymorphic, and that most mutations had occurred in exons 44 and 45. In two patients, an exon-intron boundary mutation had occurred in intron 44. Most of the variants were missense and synonymous types., Conclusion: In the present study, we have shown the occurrence of nine novel missense or synonymous variants in PKD1 gene. These data could contribute to an improved diagnostic and genetic counseling in clinical settings.
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- 2020
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9. Expression of tumor pyruvate kinase M2 isoform in plasma and stool of patients with colorectal cancer or adenomatous polyps.
- Author
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Rigi F, Jannatabad A, Izanloo A, Roshanravan R, Hashemian HR, and Kerachian MA
- Subjects
- Biomarkers, Tumor, Feces, Humans, Iran, Isoenzymes, Prospective Studies, Sensitivity and Specificity, Adenomatous Polyps diagnosis, Colorectal Neoplasms diagnosis, Pyruvate Kinase
- Abstract
Background: Tumor pyruvate kinase M2 isoform (tM2-PK), which is an isoform of PK-glycolytic enzyme and appears on the surface of cancerous proliferating cells, has been used as a diagnostic biomarker for colorectal cancer (CRC). The aim of this study was to evaluate the tM2-PK measurement test for the diagnosis of CRCs and adenomatous polyps in plasma and stool samples in an Iranian population., Methods: In this prospective study, a total of 226 stool and 178 plasma samples were received from patients referred to colonoscopy units. tM2-PK enzyme was measured using two separate ScheBo-Biotech-AG ELISA kits for stool and plasma samples., Results: According to ROC curves, in the tumor group, at the cut-off value of 4 U/ml, the sensitivity of fecal tM2-PK test was 100% and the specificity was 68%, and in the polyp group, the sensitivity and specificity were 87 and 68%, respectively. For tumor detection in plasma specimens, a cut-off value > 25 U/ml has a sensitivity and specificity of 90.9 and 91.3%, respectively. Similarly, for polyp detection, a cut-off value > 19 U/ml has a sensitivity of 96.3% and the specificity of 85.5%., Conclusions: Based on our results, a cut-off range of 4.8-8 U/ml and > 8 U/ml could be used to detect polyp and tumor in stool samples, respectively. Similarly, a cut-off range of 19-25 U/ml and > 25 U/ml is recommended in plasma samples, suggesting tM2-PK test as a non-invasive assay to diagnose CRC and adenomatous polyps.
- Published
- 2020
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10. Integration analysis of long non-coding RNA (lncRNA) role in tumorigenesis of colon adenocarcinoma.
- Author
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Poursheikhani A, Abbaszadegan MR, Nokhandani N, and Kerachian MA
- Subjects
- Adenocarcinoma genetics, Aged, Carcinogenesis genetics, Colonic Neoplasms genetics, Female, Gene Regulatory Networks, Humans, Male, MicroRNAs genetics, RNA, Messenger genetics, Adenocarcinoma pathology, Biomarkers, Tumor genetics, Carcinogenesis pathology, Colonic Neoplasms pathology, Computational Biology methods, Gene Expression Regulation, Neoplastic, RNA, Long Noncoding genetics
- Abstract
Background: Colon adenocarcinoma (COAD) is one of the most common gastrointestinal cancers globally. Molecular aberrations of tumor suppressors and/or oncogenes are the main contributors to tumorigenesis. However, the exact underlying mechanisms of COAD pathogenesis are clearly not known yet. In this regard, there is an urgent need to indicate promising potential diagnostic and prognostic biomarkers in COAD patients., Methods: In the current study, level 3 RNA-Seq and miR-Seq data and corresponding clinical data of colon adenocarcinoma (COAD) were retrieved from the TCGA database. The "limma" package in R software was utilized to indicate the differentially expressed genes. For in silico functional analysis, GO and KEGG signaling pathways were conducted. PPI network was constructed based on the STRING online database by Cytoscape 3.7.2. A ceRNA network was also constructed by "GDCRNATools" package in R software. Kaplan-Meier survival analysis (log-rank test) and ROC curve analysis were used to indicate the diagnostic and prognostic values of the biomarkers., Results: The differential expression data demonstrated that 2995 mRNAs, 205 lncRNAs, and 345 miRNAs were differentially expressed in COAD. The GO and KEGG pathway analysis indicated that the differentially expressed mRNAs were primarily enriched in canonical processes in cancer. The PPI network showed that the CDKN2A, CCND1, MYC, E2F, CDK4, BRCA2, CDC25B, and CDKN1A proteins were the critical hubs. In addition, the Kaplan-Meier analysis revealed that 215 mRNAs, 14 lncRNAs, and 39 miRNAs were associated with overall survival time in the patients. Also, the ceRNA network data demonstrated that three lncRNAs including MIR17HG, H19, SNHG1, KCNQ1OT1, MALAT1, GAS5, SNHG20, OR2A1-AS1, and MAGI2-AS3 genes were involved in the development of COAD., Conclusions: Our data suggested several promising lncRNAs in the diagnosis and prognosis of patients with COAD.
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- 2020
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11. Obesity, diabetes and the risk of colorectal adenoma and cancer.
- Author
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Soltani G, Poursheikhani A, Yassi M, Hayatbakhsh A, Kerachian M, and Kerachian MA
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- Adenocarcinoma pathology, Adenoma pathology, Adolescent, Adult, Aged, Aged, 80 and over, Child, Colonoscopy, Colorectal Neoplasms pathology, Female, Follow-Up Studies, Humans, Male, Middle Aged, Prognosis, Risk Factors, Young Adult, Adenocarcinoma etiology, Adenoma etiology, Colorectal Neoplasms etiology, Diabetes Mellitus physiopathology, Obesity complications
- Abstract
Background: Colorectal cancer (CRC) is the fourth most commonly diagnosed gastrointestinal (GI) malignancy and the third leading cause of cancer-related death worldwide. In the current case-control study, an association between diagnosis of CRC, obesity and diabetes was investigated., Methods: Demographic characteristics, colonoscopy reports, history of drug, smoking, and medical history were collected from patients referred to a colonoscopy unit. The location, size and number of the polyps were recorded during the colonoscopy. Statistically, t-test was conducted for mean comparison for the groups. Pearson's chi-squared test (χ2) was applied to categorize variables. Five classification methods based on the important clinicopathological characteristics such as age, BMI, diabetes, family history of colon cancer was performed to predict the results of colonoscopy., Results: Overall, 693 patients participated in this study. In the present study, 115 and 515 patients were evaluated for adenoma/adenocarcinoma and normal colonoscopy, respectively. The mean age of patients positive for adenoma or adenocarcinoma were significantly higher than the negative groups (p value < 0.001). Incidence of overweight and/or obesity (BMI > 25 kg/m2) were significantly higher in adenoma positive patients as compared to controls (49.9 and 0.9% respectively, p value = 0.04). The results also demonstrated a significant association between suffering from diabetes and having colon adenoma (OR = 1.831, 95%CI = 1.058-3.169, p value = 0.023). The experimental results of 5 classification methods on higher risk factors between colon adenoma and normal colonoscopy data were more than 82% and less than 0.42 for the percentage of classification accuracy and root mean squared error, respectively., Conclusions: In the current study, the occurrence of obesity measured based on BMI and diabetes in the adenoma positive patient group was significantly higher than the control group although there was no notable association between obesity, diabetes and adenocarcinoma.
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- 2019
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12. Overexpression of MicroRNA-148b-3p stimulates osteogenesis of human bone marrow-derived mesenchymal stem cells: the role of MicroRNA-148b-3p in osteogenesis.
- Author
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Mollazadeh S, Fazly Bazzaz BS, Neshati V, de Vries AAF, Naderi-Meshkin H, Mojarad M, Mirahmadi M, Neshati Z, and Kerachian MA
- Subjects
- Alkaline Phosphatase, Base Sequence, Biomarkers, Bone Marrow growth & development, Bone Marrow pathology, Cell Differentiation, Collagen Type I, Genetic Vectors, HEK293 Cells, Humans, Lentivirus genetics, Mesenchymal Stem Cells cytology, Transduction, Genetic, Bone Marrow metabolism, Mesenchymal Stem Cells metabolism, MicroRNAs genetics, MicroRNAs metabolism, Osteogenesis genetics
- Abstract
Background: Mesenchymal stem cells (MSCs) are attractive choices in regenerative medicine and can be genetically modified to obtain better results in therapeutics. Bone development and metabolism are controlled by various factors including microRNAs (miRs) interference, which are small non-coding endogenous RNAs., Methods: In the current study, the effects of forced miR-148b expression was evaluated on osteogenic activity. Human bone marrow-derived mesenchymal stem cells (BM-MSCs) were transduced with bicistronic lentiviral vector encoding hsa-miR-148b-3p or -5p and the enhanced green fluorescent protein. Fourteen days post-transduction, immunostaining as well as Western blotting were used to analyze osteogenesis., Results: Overexpression of miR-148b-3p increased the osteogenic differentiation of human BM-MSCs as demonstrated by anenhancement of mineralized nodular formation and an increase in the levels of osteoblastic differentiation biomarkers, alkaline phosphatase and collagen type I., Conclusions: Since lentivirally overexpressed miR-148b-3p increased osteogenic differentiation capability of BM-MSCs, this miR could be applied as a therapeutic modulator to optimize bone function.
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- 2019
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13. Simple and cost-effective laboratory methods to evaluate and validate cell-free DNA isolation.
- Author
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Mojtabanezhad Shariatpanahi A, Rokni P, Shahabi E, Varshoee Tabrizi F, and Kerachian MA
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- Adult, Female, Humans, Pregnancy, Cell-Free Nucleic Acids blood, Cell-Free Nucleic Acids isolation & purification, Liquid Biopsy methods, Liquid Biopsy standards
- Abstract
Objective: In the present study, we investigated different simple and cost effective methods to evaluate and validate cell free DNA (cfDNA) isolation. The ability of the QIAamp DNA Blood Mini Kit method to extract cfDNA was assessed by several approaches, including purification of endogenous cfDNA and exogenous spike-in control material, prior to plasma extraction, and followed by quantitative-PCR., Results: Using QIAamp DNA Blood Mini kit, nearly 27% (380 bp) to 35% (173 bp) cfDNA was recovered with a higher recovery of smaller size cfDNA (173 bp) in comparison to larger ones (380 bp). These simple laboratory methods can be used to assess the efficiency of any cfDNA isolation method.
- Published
- 2018
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14. Role of apoptosis in pathogenesis and treatment of bone-related diseases.
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Mollazadeh S, Fazly Bazzaz BS, and Kerachian MA
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- Apoptosis drug effects, Bone Diseases drug therapy, Bone Diseases physiopathology, Bone and Bones drug effects, Bone and Bones physiopathology, Cell Death drug effects, Cell Death physiology, Diphosphonates pharmacology, Humans, Osteoblasts drug effects, Osteoclasts drug effects, Apoptosis physiology, Bone Diseases pathology, Bone and Bones pathology, Osteoblasts pathology, Osteoclasts pathology
- Abstract
In this article, bone cells and their intercellular communications have been reviewed. Gap junctions and hemichannels are the main routes of interactions in bone tissue. They play a substantial role in survival and cell death, since pro-apoptotic signals can propagate through them. Different adhesion molecules are required for apoptosis, particularly caspase family as well as noncaspase proteases. The disruption outcome of apoptosis could result in bone-related diseases such as osteonecrosis. Anti-apoptotic strategies include inhibition of caspase, poly [ADP-ribose] polymerase (PARP), and Bcl-2 proteins as well as induction of the PKB/Akt pathway and inhibitors of apoptosis (IAP) family of proteins. Thus, understanding the mechanism of apoptosis gives detailed insights of anti-apoptotic molecular targets. Based on these targets, different treatments were designed and produced such as estrogen replacement therapy, administration of different bisphosphonates, raloxifene, calcitonin, sodium fluoride, calcium, and vitamin D. As a result, new applicable drugs for treatment of related bone problems can be proposed for clinical approach especially in the early stage of diseases.
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- 2015
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15. New insights into the pathogenesis of glucocorticoid-induced avascular necrosis: microarray analysis of gene expression in a rat model.
- Author
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Kerachian MA, Cournoyer D, Harvey EJ, Chow TY, Bégin LR, Nahal A, and Séguin C
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- Adrenal Cortex Hormones pharmacology, Animals, Apoptosis drug effects, Biomarkers metabolism, Bone and Bones drug effects, Bone and Bones metabolism, Bone and Bones pathology, Collagen Type II metabolism, Female, Femur Head Necrosis metabolism, Male, Proteins metabolism, Rats, Rats, Wistar, alpha-Macroglobulins metabolism, Disease Models, Animal, Femur Head Necrosis chemically induced, Femur Head Necrosis genetics, Glucocorticoids adverse effects, Oligonucleotide Array Sequence Analysis
- Abstract
Introduction: Avascular necrosis of the femoral head (ANFH) occurs variably after exposure to corticosteroids. Microvascular thrombosis is a common pathological finding. Since systemic thrombophilia is only weakly linked with ANFH, we propose that microvascular vessel pathology may be more related to local endothelial dysfunction and femoral head apoptosis. Corticosteroid effects on the endothelium and resultant apoptosis have been reported. We hypothesize that corticosteroids contribute to a differential gene expression in the femoral head in rats with early ANFH., Methods: Besides bone marrow necrosis, which is a common sign in ANFH and reported in the early stages, we include the presence of apoptosis in this study as a criterion for diagnosing early disease. Forty Wistar Kyoto (WKY) rats were randomized to either a corticosteroid-treated group or an age-matched control group for six months. After sacrifice, the femoral heads were examined for ANFH. Total mRNA was extracted from femoral heads. Affymetrix exon array (Santa Clara, CA, USA) was performed on 15 selected RNA samples. Validation methods included RT-PCR and immunohistochemistry (IHC)., Results: Although rat exon array demonstrated a significant upregulation of 51 genes (corticosteroid(+)/ANFH(+) VS control), alpha-2-macroglobulin (A2M) gene was particularly over-expressed. Results were validated by RT-PCR and IHC. Importantly, A2M is known to share vascular, osteogenic and cartilage functions relevant for ANFH., Conclusions: The findings suggest that corticosteroid-induced ANFH in rats might be mediated by A2M. Investigation of A2M as a potential marker, and a treatment target, for early ANFH should be carried out.
- Published
- 2010
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