Iranian Biomedical Journal
Volume:22 Issue: 6, Oct 2018

Like the biological clock in the body, replication of each cell type (even different cells of the same organism) follows a timing program. Abnormal function of this timer could be an alarm for a disease like cancer. DNA replication starts from a specific point on the chromosome that is called the origin of replication. In contrast to prokaryotes in which DNA replication starts from a single origin, eukaryotic DNA replication starts from many origins scattered along the chromosomes. Budding yeast contains 300 origins, whereas fission yeast has 1,100, and the numbers of replication origins for human increase to over 20,000. These origins are fired in a coordinated manner, and there are spatial and temporal disciplines for this process, which happens in the S phase of the cell cycle. It was known that eukaryotic cells prepare all these potential origins during the G1 phase of the cell cycle but utilize only a portion of these origins during S phase. Furthermore, firing some of these origins are delayed until the mid and late phases of the S phase. Coordinated activation of these origins occurs under “Replication Timing Program”. The segments of the chromosome containing co-regulated origins that fire simultaneously are named “Replication Timing Domains”, ranging in size from 100 kb to 1 Mb. Replication timing is determined at a specific time in the early G1 phase that is called Timing Decision Point (TDP). Studies have shown that major chromosome repositioning occurs at TDP. Generally, replication timing domains are classified into three classes including Early, Mid and Late...

Scientometrics is a discipline that analyzes scientific publications to explore the structure and growth of science. In this work, the quantitative evaluation of the productivity of the Iranian Biomedical Journal (IBJ) is reviewed. The analysis was done based on a cross-sectional descriptive and an analytical scientometric study. Data were collected from PubMed, Scopus, and Scimago Databases (2000-2017). Scopus and Scimago were used for data search and feature analysis. Analyzed scientometric indicators included the number of citations, publications, CiteScore, SJR (Scimago Journal Rank), SNIP (source normalized impact per paper), self-citation, and Q (quartile) trend. The evaluation of 586 documents, published in IBJ from 2000 to 2017, revealed that most of these documents (99.7%) have been published in the areas of biochemistry, genetics, and molecular biology, which yielded to an upgrade in Journal Q ranking from Q4 (in 2000) to Q2 (in 2016). Nearly all of the scientometric indicators, evaluated in this study, were found on the rise. Therefore, a growing trend from Q2 to Q1 is predicted for the near future. It is recommended that the journal focuses on a specific subject area to improve the indicators and quality of the journal, in a timely manner.

Differential expression profile of microRNAs (miRNAs) could be a diagnosis signature for monitoring gastric cancer (GC) progression. In this study, we focus on the comparison of expression levels of miR-21, miR-25, miR-93, miR-106b, and miR-375 during the sequential pattern of GC development, including normal gastric, gastric dysplasia, and GC sample. We used SYBR Green-based quantitative-PCR to quantify miRNAs expression. Our analysis revealed the increased expression levels of miR-21 (p = 0.034), miR-25 (p = 0.0003), miR-93 (p = 0.0406), and miR-106b (p = 0.023) in GC samples. In addition, GC patients with positive lymph node metastasis showed the up-regulation of miR-25, miR-93, and miR-106b (p < 0.05). Our findings suggested that the expression of miR-21, miR-25, miR-93, and miR-106b altered in GC, and some of them may be further investigated as biomarkers for GC early detection and prognosis prediction.

IgA nephropathy (IgAN) is the most common primary glomerulonephritis diagnosed based on renal biopsy. Mesangial IgA deposits along with the proliferation of mesangial cells are the histologic hallmark of IgAN. Non-invasive diagnostic tools may help to prompt diagnosis and therapy. The discovery of potential and reliable urinary biomarkers for diagnosis of IgAN depends on applying robust and suitable models. Applying two multivariate modeling methods on a urine proteomic dataset were obtained from IgAN patients, and comparison of the results of these methods were the purpose of this study. Two models were constructed for urinary protein profiles of 13 patients and 8 healthy individuals, based on sparse linear discriminant analysis (SLDA) and elastic net (EN) regression methods. A panel of selected biomarkers with the best coefficients were proposed and further analyzed for biological relevance using functional annotation and pathway analysis. Transferrin, α1-antitrypsin, and albumin fragments were the most important up-regulated biomarkers, while fibulin-5, YIP1 family member 3, prasoposin, and osteopontin were the most important down-regulated biomarkers. Pathway analysis revealed that complement and coagulation cascades and extracellular matrix-receptor interaction pathways impaired in the pathogenesis of IgAN. SLDA and EN had an equal importance for diagnosis of IgAN and were useful methods for exploring and processing proteomic data. In addition, the suggested biomarkers are reliable candidates for further validation to non-invasive diagnose of IgAN based on urine examination.

Chinese hamster ovary (CHO) cell line is considered as the most common cell line in the biopharmaceutical industry because of its capability in performing efficient post-translational modifications and producing the recombinant proteins, which are similar to natural human proteins. The optimization of the upstream process via different feed strategies has a great impact on the target molecule expression and yield. To determine and understand the molecular events beneath the feed effects on the CHO cell, a label-free quantitative proteomic analysis was applied. The proteome changes followed by the addition of a designed amino acid feed to the monoclonal antibody producing CHO cell line culture medium were investigated. The glutathione synthesis, the negative regulation of the programmed cell death, proteasomal catabolic process, and the endosomal transport pathway were up-regulated in the group fed with a designed amino acid feed compared to the control group. Our findings could be helpful to identify new targets for metabolic engineering.

The human immunodeficiency virus type 1 (HIV-1) is an infectious viral agent that gradually extinguishes the immune system, resulting in acquired immune deficiency syndrome (AIDS). The aim of this study was to construct an RNA-positive control based on armored (AR) RNA technology, using HIV-1 RNA as a model. The MS2 maturase, a coat protein gene (at positions 1765 to 1787) and HIV-1 pol gene were cloned into pET-32a plasmid. The prepared plasmid was transformed into Escherichia coli strain BL2 (DE3), and the expression of the construct was induced by 1 mM of isopropyl-L-thio-D-galactopyranoside (IPTG) at 37 °C for 16 h to obtain the fabricated AR RNA. The AR RNA was precipitated and purified using polyethylene glycol and Sephacryl S-200 chromatography. The stability of AR RNA was evaluated by treatment with DNase I and RNase A and confirmed by transmission electron microscopy and gel agarose electrophoresis. Tenfold serial dilution of AR RNA from 101 to 105 was prepared. Real-time PCR assays had a range of detection between 101 and 105. In addition, R2 value was 0.998, and the slope of the standard curve was -3.33. Prepared AR RNA, as a positive control, could be used as a basis for launching an in-house HIV-1 virus assay and other infectious agents. It can be readily available to laboratories and HIV research centers. The AR RNA is non-infectious and highly resistant to ribonuclease enzyme and can reduce the risk of infection in the clinical laboratory.

Drug resistance is a major public health problem and a threat to progress made in bovine tuberculosis care and control worldwide. This study aimed at evaluating anti-mycobacterial and synergistic activity of some medicinal plants that were selected by cheminformatics studies against Mycobacterium bovis. Considering the strong synergistic antimycobacterial action of oleanolic acid in combination with tuberculosis drugs, NCBI database was explored to find the compounds with over 80% similarity to oleanolic acid, called S1. Plants containing S1-type compounds were traced to and resulted in five plants, including Datura stramonium, Boswellia serrata Lavandula stoechas, Rosmarinus officinalis, and Thymus vulgaris, as experimental samples. Crude extracts were prepared by percolation using 80% ethanol or as the product of a pharmaceutical company. The extracts were screened against Mycobacterium bovis using broth microdilution method and Alamar Blue Assay. Extracts from these plants were used in combination with isoniazid and ethambutol to investigate the possibility of synergy with respect to antimycobacterial activity. The extracts from D. stramonium, B. serrata a, L. stoechas, R. officinalis, and T. Thymus vulgaris showed antimycobacterial activity of 375, 125, 250, 187.5, 500 µg/ml, respectively. The best synergistic results were for L. stoechas and D. stramonium in combination with ethambutol, the fractional inhibitory concentration index was 0.125 µg/ml for both. The observed antimycobacterial and synergistic activities are completely novel and obtained from targeted screening designed according to cheminformatics strategy. As for the synergistic action of the extracts, they could be used as supplements in bTB treatment.

Merosin-deficient congenital muscular dystrophy (MDC1A) is a rare autosomal recessive genetic disease occurred due to mutations in the LAMA2 gene. This study investigated the molecular genetics of three Iranian MDC1A patients who manifested hypotonia, muscle weakness at birth, elevated levels of creatine kinase, and normal magnetic resonance imaging before the age of six months. Peripheral blood samples were collected from three unrelated patients and their families after obtaining informed written consents. Genomic DNA was extracted and sequenced using next-generation sequencing, followed by Sanger confirmation. Sequencing results revealed a known missense mutation, c.8665G>A, and two novel heterozygous sequencing variants affecting splicing, c.397-4_c.478del and c.7452-1G>A, in the LAMA2 gene. Reverse transcriptase-PCR analysis showed that a new intronic variant, c.7452-1G>A, produced aberrant splicing pattern in the patient. This study expands the mutation spectrum of LAMA2 and assists in the diagnosis, genetic counseling, and prenatal diagnosis of the affected families.

Chanarin-Dorfman syndrome (CDS) is a rare autosomal recessive metabolic disorder caused by mutations in gene encoding the domain-5 of α/β-hydrolase enzyme (ABHD5). It is known as a natural lipid storage disorder arising from impaired lipid metabolism often characterized by hepatomegaly, myopathy, ataxia, non-bullous ichthyosiform erythroderma, hearing loss, and mental retardation. In the present study, we report two affected 28-month-old monozygotic twin boys as new cases of CDS. Genetic analysis was performed in patients, and the results showed a homozygote deletion in exon 4 of ABHD5. According to the the American College of Medical Genetics and Genomics, this variant is categorized as a pathogenic variant.