Author: Mohammad S. Hashemzadeh

Concise Review on Modulation Mechanism of Matrix Metalloproteinase via Oncoviruses in Aggressiveness of Malignancies

Matrix metalloproteinases (MMPs) are a member of the protein family intimately associated with zinc-containing endopeptidases, which are the main proteases implicated in extracellular matrix (ECM) degradation. The high ability of MMPs in the degradation of extracellular proteins is an important event in many normal biological as well as pathologic processes, including tumor progression, tissue repair, wound healing, developmental morphogenesis, and inflammatory diseases. This review is focused on the description of the modulation mechanism of MMPs via oncoviruses. Up to now, a large number of oncogenic viruses have been detected and recognized as etiologic factors of multiple human cancers. Actually, by expression of several viral oncoproteins of tumorigenic viruses with the simple genetic system, we are able to deregulate or modulate the pathways of cell transformation procedure in malignancy. In brief, upregulated expression of MMPs genes by direct (through DNA binding) , as well as indirect interactions (by activating PI-3K/AKT, ERK/MAPK, IFN/JAK/STAT, JNK, NF-κB signaling pathways and/or immune response) with tumorigenic viruses, have a noticeable role in the proliferation of cells, as well as angiogenesis, mobility, EMT, invasiveness, and metastatic features. In fact, the growth of tumor-related researchers offers a future perspective for the efficiency of targeted, molecular-based therapies and its anticancer effects via diverse mechanisms such as the suppression of viral oncoproteins.

Deregulation of the Hippo Signaling Pathway in Virus-Associated Cancer

Hippo signaling has been recognized as a newly identified tumor suppressor signaling pathway that can regulate cellular processes including regeneration, cell death, differentiation, and development. Its dysregulation through overexpression of YAP (Yes-associated protein) and TAZ (PDZ-binding motif) as two main oncogenic factors of the Hippo pathway has a crucial role in several cancers. Because of the limited prognosis and therapeutic targets, further understanding of molecular pathways involved in tumorigenesis is one of the interesting issues in studies. Here, we demonstrated that some viruses, through dysregulation of the Hippo signaling pathway can be implicated in transformation, metastasis, and chemotherapeutic drug resistance in virus-related cancer and also help processes involved in the pathogenesis of viral infection such as persistence.

The relationship between a previous infectious disease caused by the influenza, herpes simplex or Epstein-Barr viruses as the biological threatening agents with recurrent episodes of multiple sclerosis

Although multiple sclerosis (MS) is the most common neurological disease of young adults, afflicting hundreds of thousands of people worldwide, its pathogenesis is still only incompletely understood. There seems to be substantial heterogeneity in disease mechanisms, but in the majority of cases an autoimmune origin or at least a decisive autoimmune component is postulated. Therefore, pathogenic research focuses on different players programmed by the immune system. In this study, biomarkers such as Human myxovirus resistance protein A (MxA), Anti-EBNA antibody and Interleukin S10-12- 17 have been tested. Study of hypotheses show that: Interleukin levels in the blood of MS patients in the experimental group (patients with recurrence) is higher than controls (patients without recurrence condition). The level of anti-EBNA antibody in MS patients in other groups (patients with recurrent) and control group (patients without recurrence condition) is high. The level of the human myxovirus resistance protein A (MxA) in patients with multiple sclerosis in the experimental group (patients with recurrence) is less than the control group (patients without recurrence condition). The level of anti-EBNA antibody in MS patients in other groups (patients with recurrent) and control group (patients without recurrence condition) is high. Finally, there is a significant relationship between viral infection diseases and recurrent multiple sclerosis.

Investigating the Role of Adenovirus, Herpes Simplex 1, 2, and Varicella Zoster Virus in Incidence of Conjunctivitis in Tehran, Iran

Conjunctivitis is one of the most common ocular diseases across the world. In this study, the prevalence of viral Conjunctivitis in patients who were referred to the Eye specialized Hospitals was evaluated. Some of the most important viruses that cause conjunctivitis are Human Adenoviruses (HAdV), Herpes Simplex 1, 2 (HSV-1, HSV-2), and Varicella Zoster Virus (VZV). The clinical diagnosis of eye viral infections is difficult and often controversial. Thus, research to experiment with these causative factors is of pivotal importance. In this cross-sectional study, 200 conjunctival swab samples were collected from symptomatic patients with signs of conjunctivitis who had been referred to two hospitals. After DNA extraction, Multiplex Real-Time PCR was carried out in two separate reactions for each sample. Among 200 collected samples, 34 (17%) and 8 (4%) were positive for Adenovirus and HSV-1 DNA, respectively. There were no HSV-2 and VZV conjunctivitis. No significant correlation was identified between gender and conjunctivitis (P-value: 0.845); however, there was a close correlation between age and conjunctivitis (P- value: 0.05). In this study, 66.3% of Adenoviral conjunctivitis occurs in the summer compared to 33.7% in spring. No significant seasonal variation was observed for HSV-1. Our results showed that adenovirus has a key role in causing viral conjunctivitis.

The emergence of nanotechnology and a revolution in diagnostic methods of biological threat agents

Nanotechnology is applied in wide-ranging fields including energy, information technology, consumables, medicine, etc. Nanomedicine includes the medical applications of nanomaterials in the fields of diagnosis and treatment. This paper focuses on the application of nanotechnology in medical diagnostics for which the main applications of nanomedicine include the detection and discovery of specific biomarkers and rapid identification of biological agents. The

Peptide nucleic acid (PNA) as a novel tool in the detection and treatment of biological threatening diseases

Peptide Nucleic Acids (PNAs) are nanostructures similar to nucleic acid molecules (synthetic DNA/RNA analogs) wherein the negatively charged backbone (sugar-phosphate) present in DNA/RNA molecules is replaced by a backbone without polyamide or peptide charge. Later, it was found that PNAs containing both purine and pyrimidine bases form highly stable duplexes with DNA and RNA. Although it is not as stable as 2PNA/DNA triplexes containing a homopyrimidine strand, it is still more stable than DNA/DNA and/or DNA/RNA duplexes. The unique characteristics of PNAs add new aspects to these nanostructures relative to conventional analogs to make them appropriate for molecular biology studies. The most important applications include the use of these nanostructures in the detection and treatment of diseases caused by threatening biological agents using the antisense/antigen technology and as genetic regulator drugs.

Aptamer as a proper alternative instead of monoclonal antibody in diagnosis and neutralization of menacing biological agents

Of the major threats to contemporary mankind, is the use of very dangerous and lethal biological agents as the biological weapons. The first step in confronting with this serious threat after prevention, is the accurate and rapid detection of this agents and neutralization of them. In this article, the role of molecules known as aptamer, has been studied in biological defense against these menacing biological agents. Traditional methods for detection of these agents are based primarily on immuno-affinity assays and the use of antibody molecules. While the modern methods, based on aptamer-affinity assays, are being replaced with traditional methods, due to the abundant advantages of them. The selection and preparation method of specific aptamer with high binding affinity to these biological agents is known as SELEX and the use of magnetic nanoparticles to perform this procedure (Mag-SELEX) is very common. The isolated aptamers with high specificity can also be used in neutralization and inhibition of menacing agents function, in addition to, quick and accurate diagnosis of these agents, utilizing them in nano-biosensors, based on aptamers (as the nano- aptasensors).

Development of quantitative real-time RT-PCR assay for detection and viral load determination of Crimean-Congo Hemorrhagic Fever (CCHF) virus

Background and Aim: The CCHF (Crimean-Congo hemorrhagic fever) virus causes a severe disease in human with a case fatality rate of up to 50%. Since, there is no specific treatment or approved vaccine against CCHF viral infections, an accurate and early detection as well as a reliable surveillance and quantitative determination of viral load is necessary for patient improvement and case management. In this research, our aim was to develop a probe based one-step real- time reverse-transcription polymerase chain reaction (rRT-PCR) assay for in-house quantitative detection of CCHF virus. Methods: At first, the highly conserved S-fragment sequence of CCHF virus genome was adapted from GenBank and the specific probe and primers targeting this region were designed. Then, viral RNAs were extracted from 37 blood samples of different patients from east of Iran (Zahedan). The specificity and sensitivity of the probe and primers were also evaluated in positive blood samples, confirmed to have CCHF virus. A standard (PTG19-T vector containing S-fragment) for quantization was also constructed and the viral load was determined in some of positive samples. Results: From a total of 37 suspicious blood samples, 15 samples were confirmed to be positive for CCHF virus by this probe based one-step rRT-PCR assay and no false-positive result was detected according to sequencing data. The predicted fragment of 176 bp was also confirmed in all positive samples by gel-based electrophoresis analysis. The assay was linear between 10 to 103 copy numbers per each microliter of extracted plasmid for this technique and the viral load determined in one of patient blood samples was 55,000 viral particles per each milliliter, for example. Bioinformatics and experimental evaluations approved the specificity of this assay. The LOD of the assay was 10 (or fewer) copy numbers of viral genome per each microliter of the extracted genome. Conclusions: This research showed that the developed probe based one-step rRT-PCR assay is a specific, rapid, sensitive and the simple tool for detection and viral load determination of the CCHF virus.