Publications by authors named "Javid Sadri Nahand"

38 Publications

Oncogenic viruses and chemoresistance: What do we know?

Pharmacol Res 2021 Jun 11;170:105730. Epub 2021 Jun 11.

Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran. Electronic address:

Chemoresistance is often referred to as a major leading reason for cancer therapy failure, causing cancer relapse and further metastasis. As a result, an urgent need has been raised to reach a full comprehension of chemoresistance-associated molecular pathways, thereby designing new therapy methods. Many of metastatic tumor masses are found to be related with a viral cause. Although combined therapy is perceived as the model role therapy in such cases, chemoresistant features, which is more common in viral carcinogenesis, often get into way of this kind of therapy, minimizing the chance of survival. Some investigations indicate that the infecting virus dominates other leading factors, i.e., genetic alternations and tumor microenvironment, in development of cancer cell chemoresistance. Herein, we have gathered the available evidence on the mechanisms under which oncogenic viruses cause drug-resistance in chemotherapy.
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http://dx.doi.org/10.1016/j.phrs.2021.105730DOI Listing
June 2021

Plant-based vaccines and cancer therapy: Where are we now and where are we going?

Pharmacol Res 2021 Jul 15;169:105655. Epub 2021 May 15.

Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran. Electronic address:

Therapeutic vaccines are an effective approach in cancer therapy for treating the disease at later stages. The Food and Drug Administration (FDA) recently approved the first therapeutic cancer vaccine, and further studies are ongoing in clinical trials. These are expected to result in the future development of vaccines with relatively improved efficacy. Several vaccination approaches are being studied in pre-clinical and clinical trials, including the generation of anti-cancer vaccines by plant expression systems.This approach has advantages, such as high safety and low costs, especially for the synthesis of recombinant proteins. Nevertheless, the development of anti-cancer vaccines in plants is faced with some technical obstacles.Herein, we summarize some vaccines that have been used in cancer therapy, with an emphasis on plant-based vaccines.
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http://dx.doi.org/10.1016/j.phrs.2021.105655DOI Listing
July 2021

Cell death pathways and viruses: Role of microRNAs.

Mol Ther Nucleic Acids 2021 Jun 19;24:487-511. Epub 2021 Mar 19.

Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran.

Viral infections lead to the death of more than a million people each year around the world, both directly and indirectly. Viruses interfere with many cell functions, particularly critical pathways for cell death, by affecting various intracellular mediators. MicroRNAs (miRNAs) are a major example of these mediators because they are involved in many (if not most) cellular mechanisms. Virus-regulated miRNAs have been implicated in three cell death pathways, namely, apoptosis, autophagy, and anoikis. Several molecules (e.g., BECN1 and B cell lymphoma 2 [BCL2] family members) are involved in both apoptosis and autophagy, while activation of anoikis leads to cell death similar to apoptosis. These mechanistic similarities suggest that common regulators, including some miRNAs (e.g., miR-21 and miR-192), are involved in different cell death pathways. Because the balance between cell proliferation and cell death is pivotal to the homeostasis of the human body, miRNAs that regulate cell death pathways have drawn much attention from researchers. miR-21 is regulated by several viruses and can affect both apoptosis and anoikis via modulating various targets, such as PDCD4, PTEN, interleukin (IL)-12, Maspin, and Fas-L. miR-34 can be downregulated by viral infection and has different effects on apoptosis, depending on the type of virus and/or host cell. The present review summarizes the existing knowledge on virus-regulated miRNAs involved in the modulation of cell death pathways. Understanding the mechanisms for virus-mediated regulation of cell death pathways could provide valuable information to improve the diagnosis and treatment of many viral diseases.
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http://dx.doi.org/10.1016/j.omtn.2021.03.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056183PMC
June 2021

Acute and post-acute phase of COVID-19: Analyzing expression patterns of miRNA-29a-3p, 146a-3p, 155-5p, and let-7b-3p in PBMC.

Int Immunopharmacol 2021 Apr 6;97:107641. Epub 2021 Apr 6.

Department of Virology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Background: When a new pathogen, such as severe acute respiratory syndrome coronavirus 2, appears all novel information can aid in the process of monitoring and in the diagnosis of the coronavirus disease (COVID-19). The aim of the current study is to elucidate the specific miRNA profile which can act as new biomarkers for distinguishing acute COVID-19 disease from the healthy group and those in the post-acute phase of the COVID-19 disease.

Methods: The expression level of selected miRNAs including let-7b-3p, miR-29a-3p, miR-146a-3p and miR-155-5p were evaluated in peripheral blood mononuclear cells (PBMCs) of COVID-19 patients, in both the acute and post-acute COVID-19 phase of the disease and healthy groups, by real-time PCR assays. Specificity and sensitivity of miRNAs was tested by receiver operating characteristic (ROC) analysis in COVID-19 patients.

Results: The expression level of all miRNAs in COVID-19 patients was significantly higher than in the healthy group. Therefore, the expression pattern of miR-29a-3p, miR-146a-3p and let-7b-3p in the post-acute COVID-19 phase was significantly different from the acute COVID-19 phase. ROC analyses demonstrated that miR-29a-3p, -155-5p and -146a-3p may serve as the novel biomarker for COVID-19 diagnosis with high specificity and sensitivity. In addition, miR-29a-3p, and -146a-3p can maybe act as novel biomarkers for distinguishing acute from post-acute phase of COVID-19 disease.

Discussion: The difference in miRNA expression pattern between COVID-19 patients and those in the healthy group, and between acute COVID-19 with post-acute COVID-19, suggested that cellular miRNAs could be used as promising biomarkers for diagnosis and monitoring of COVID-19.
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http://dx.doi.org/10.1016/j.intimp.2021.107641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8023203PMC
April 2021

Chitosan-Based Nanoparticles Against Viral Infections.

Front Cell Infect Microbiol 2021 17;11:643953. Epub 2021 Mar 17.

Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran.

Viral infections, in addition to damaging host cells, can compromise the host immune system, leading to frequent relapse or long-term persistence. Viruses have the capacity to destroy the host cell while liberating their own RNA or DNA in order to replicate within additional host cells. The viral life cycle makes it challenging to develop anti-viral drugs. Nanotechnology-based approaches have been suggested to deal effectively with viral diseases, and overcome some limitations of anti-viral drugs. Nanotechnology has enabled scientists to overcome the challenges of solubility and toxicity of anti-viral drugs, and can enhance their selectivity towards viruses and virally infected cells, while preserving healthy host cells. Chitosan is a naturally occurring polymer that has been used to construct nanoparticles (NPs), which are biocompatible, biodegradable, less toxic, easy to prepare, and can function as effective drug delivery systems (DDSs). Furthermore, chitosan is Generally Recognized as Safe (GRAS) by the US Food and Drug Administration (U.S. FDA). Chitosan NPs have been used in drug delivery by the oral, ocular, pulmonary, nasal, mucosal, buccal, or vaginal routes. They have also been studied for gene delivery, vaccine delivery, and advanced cancer therapy. Multiple lines of evidence suggest that chitosan NPs could be used as new therapeutic tools against viral infections. In this review we summarize reports concerning the therapeutic potential of chitosan NPs against various viral infections.
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http://dx.doi.org/10.3389/fcimb.2021.643953DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011499PMC
July 2021

The role of viral and bacterial infections in the pathogenesis of IPF: a systematic review and meta-analysis.

Respir Res 2021 Feb 12;22(1):53. Epub 2021 Feb 12.

Department of Microbiology, Faculty of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease. Several risk factors such as smoking, air pollution, inhaled toxins, high body mass index and infectious agents are involved in the pathogenesis of IPF. In the present study, this meta-analysis study investigates the prevalence of viral and bacterial infections in the IPF patients and any possible association between these infections with pathogenesis of IPF.

Methods: The authors carried out this systematic literature review from different reliable databases such as PubMed, ISI Web of Science, Scopus and Google Scholar to December 2020.Keywords used were the following "Idiopathic pulmonary fibrosis", "Infection", "Bacterial Infection" and "Viral Infection", alone or combined together with the Boolean operators "OR", "AND" and "NOT" in the Title/Abstract/Keywords field. Pooled proportion and its 95% CI were used to assess the prevalence of viral and bacterial infections in the IPF patients.

Results: In this systematic review and meta-analyses, 32 studies were selected based on the exclusion/inclusion criteria. Geographical distribution of included studies was: eight studies in American people, 8; in European people, 15 in Asians, and one in Africans. The pooled prevalence for viral and bacterial infections w ere 53.72% (95% CI 38.1-69.1%) and 31.21% (95% CI 19.9-43.7%), respectively. The highest and lowest prevalence of viral infections was HSV (77.7% 95% CI 38.48-99.32%), EBV (72.02%, 95% CI 44.65-90.79%) and Influenza A (7.3%, 95% CI 2.66-42.45%), respectively. Whereas the highest and lowest prevalence in bacterial infections were related to Streptococcus sp. (99.49%, 95% CI 96.44-99.9%) and Raoultella (1.2%, 95% CI 0.2-3.08%), respectively.

Conclusions: The results of this review were confirmed that the presence of viral and bacterial infections are the risk factors in the pathogenesis of IPF. In further analyses, which have never been shown in the previous studies, we revealed the geographic variations in the association strengths and emphasized other methodological parameters (e.g., detection method). Also, our study supports the hypothesis that respiratory infection could play a key role in the pathogenesis of IP.
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http://dx.doi.org/10.1186/s12931-021-01650-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880524PMC
February 2021

As Evidence-Based Tumorigenic Role of Epstein-Barr Virus miR-BART1-3p in Neurological Tumors.

Asian Pac J Cancer Prev 2021 Jan 1;22(1):257-266. Epub 2021 Jan 1.

Department of Virology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Introduction: Central nervous system tumors are a diverse group of tumors that account for 2% of all adult cancers and 17% of childhood malignancies. Several internal and external risk factors are involved in the development of this cancer such as viral infections. The aim of this study was to the determination of the EBV infection frequency and the expression level of miR-122 and miR-BART in CNS tumors samples.

Methods: One hundred and thirty-eight  fresh tissue sample (106 case and 32 control) was collected from CNS specimens. The presence of Epstein-Barr virus (EBV) DNA was examined by PCR assay and the expression level of miR-122 and miR-BART were evaluated by using real-time PCR assay in CNS tissue samples.

Results: EBV DNA was detected in 17% (18 of 106) of tumors tissue samples and 6.4% (2 of 32) of control samples. according to results, there was a significant relationship between the presence of EBV-DNA with CNS tumors. Additionally, the expression level of miR-122 was significantly downregulated in the EBV-positive sample compared to that of the EBV-negative sample. Also, the level of EBV-BART1-3p expression was significantly higher in EBV-positive tumors samples than EBV-positive normal samples.

Conclusion: The results of this study suggest that the EBV could change the condition of cancer cells by altering the expression of miR-122 and EBV-BART1-3p and maybe contribute to the development of cancer cells. However, the role of viral infections in CNS cancer requires further studies. 
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http://dx.doi.org/10.31557/APJCP.2021.22.1.257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184183PMC
January 2021

The role of Th17 cells in viral infections.

Int Immunopharmacol 2021 Feb 5;91:107331. Epub 2021 Jan 5.

Immunology Research Center, Tabriz University of Medical Sciences, ZIP Code 15731 Tabriz, Iran; Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, ZIP Code 15731 Tabriz, Iran; Department of Virology, Faculty of Medicine, Tabriz University of Medical Sciences, ZIP Code 15731 Tabriz, Iran. Electronic address:

The present review provides an overview of recent advances regarding the function of Th17 cells and their produced cytokines in the progression of viral diseases. Viral infections alone do not lead to virus-induced malignancies, as both genetic and host safety factors are also involved in the occurrence of malignancies. Acquired immune responses, through the differentiation of Th17 cells, form the novel components of the Th17 cell pathway when reacting with viral infections all the way from the beginning to its final stages. As a result, instead of inducing the right immune responses, these events lead to the suppression of the immune system. In fact, the responses from Th17 cells during persistent viral infections causes chronic inflammation through the production of IL-17 and other cytokines which provide a favorable environment for tumor growth and its development. Additionally, during the past decade, these cells have been understood to be involved in tumor progression and metastasis. However, further research is required to understand Th17 cells' immune mechanisms in the vast variety of viral diseases. This review aims to determine the roles and effects of the immune system, especially Th17 cells, in the progression of viral diseases; which can be highly beneficial for the diagnosis and treatment of these infections.
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http://dx.doi.org/10.1016/j.intimp.2020.107331DOI Listing
February 2021

The role of HPV gene expression and selected cellular MiRNAs in lung cancer development.

Microb Pathog 2021 Jan 7;150:104692. Epub 2020 Dec 7.

Department of Microbiology, Faculty of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran. Electronic address:

Background: The high mortality rate of lung cancer can be justified that strong need to explore new aspect of tumor biology. Human papillomavirus (HPV) has been detected as risk factor for the development of lung cancer. The aim of this study was to determine the role of HPV and cellular/miRNAs genes expression in the epithelial-mesenchymal transition (EMT) and development of lung cancer.

Methods: In this case-control study, 109 lung cancer tissue and 52 controls were included. We analyzed the presence of HPV infection, its genotypes (in positive samples) and the expression of viral genes (E2, E6 and E7). Also, We examined the expression of celluar factors including (a) p53 and retinoblastoma (Rb) (as anti-carcinogenic genes), (b) EMT related genes, (c) selected miRNAs.

Results: Our results reported 51.4% and 23.1% of HPV genome in tumor tissues and control tissues samples, respectively. There was a significant association between the HPV positive status and lung cancer (OR = 3.26, 95% C.I = 1.47-7.02, P = 0.001). HPV type 16 was the most prevalent genotype in tissues. The expression of p53, RB, TIMP1, CCNG-1, E-cad and PTPN13 were decreased while MMP-2 and N-cad were increased in HPV-positive tumor/control tissues compared to HPV-negative tissues. Also, among miRNAs, let-7, miR-23, miR-34, miR-125, miR-146 were downregulated and miR-20, miR-424 were upregulated in HPV-positve tissues compared to HPV-negative tissues.

Conclusion: This study demonstrated that HPV infection and interaction with cellular genes and miRNAs promote EMT which involved in the lung cancer development.
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http://dx.doi.org/10.1016/j.micpath.2020.104692DOI Listing
January 2021

Human papillomavirus and prostate cancer: The role of viral expressed proteins in the inhibition of anoikis and induction of metastasis.

Microb Pathog 2021 Mar 18;152:104576. Epub 2020 Oct 18.

Department of Virology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran. Electronic address:

Background: The aim of this study is to address the role of HPV in prostate cancer (PCa) development through the inducement of resistance to anoikis.

Methods: In this case-control study, prostate tissues and blood samples were collected from 116 individuals, including 72 cases with PCa and 44 non-malignant prostate tissue samples as a control group. The expression level of HPV genes (E2, E6, and E7) and cellular genes including anti-apoptotic mediators (Bcl-2 and survivin), tumor suppressor proteins (Rb and p53), and some mediators involved in anoikis resistance and invasiveness (E-cadherin, N-cadherin, Twist, PTPN13 and SLUG) were evaluated.

Results: HPV genome was identified in 36.1% cases and 15.9% control samples, additionally there was found to be a statistic significant association between the presence of HPV and PCa (OR = 1.64, 95% C.I = 0.8-1.8, P-value = 0.023). HPV genotype 16 and 18 were the most prevalent genotype in both in the PCa group and the control group. The expression level of the tumor suppressor proteins (Rb and p53) and anti-apoptotic mediators (Bcl-2 and Survivin) were significantly decreased and increased, respectively, in the HPV-positive specimens compared to the HPV-negative specimens. Furthermore, the mean expression level of N-cadherin, SLUG, and TWIST in the HPV-positive specimens was higher than HPV-negative specimens while the mean expression level of PTPN-13 and E-cadherin genes in the HPV-positive specimens was lower than HPV-negative specimens.

Conclusion: Our study suggests that HPV infection may be involved in the development of PCa metastases by modulating anoikis resistance related genes.
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http://dx.doi.org/10.1016/j.micpath.2020.104576DOI Listing
March 2021

The association between HPV gene expression, inflammatory agents and cellular genes involved in EMT in lung cancer tissue.

BMC Cancer 2020 Sep 24;20(1):916. Epub 2020 Sep 24.

Department of Microbiology, Faculty of Medicine, Kermanshah University of Medical Sciences, PO Box 6716777816, Razi Blvd, Kermanshah, Iran.

Background: Lung cancer is a leading cause of cancer morbidity and mortality worldwide. Several studies have suggested that Human papillomavirus (HPV) infection is an important risk factor in the development of lung cancer. In this study, we aim to address the role of HPV in the development of lung cancer mechanistically by examining the induction of inflammation and epithelial-mesenchymal transition (EMT) by this virus.

Methods: In this case-control study, tissue samples were collected from 102 cases with lung cancer and 48 controls. We examined the presence of HPV DNA and also the viral genotype in positive samples. We also examined the expression of viral genes (E2, E6 and E7), anti-carcinogenic genes (p53, retinoblastoma (RB)), and inflammatory cytokines in HPV positive cases.

Results: HPV DNA was detected in 52.9% (54/102) of the case samples and in 25% (12/48) of controls. A significant association was observed between a HPV positive status and lung cancer (OR = 3.37, 95% C.I = 1.58-7.22, P = 0.001). The most prevalent virus genotype in the patients was type 16 (38.8%). The expression of p53 and RB were decreased while and inflammatory cytokines were increased in HPV-positive lung cancer and HPV-positive control tissues compared to HPV-negative lung cancer and HPV-negative control tissues. Also, the expression level of E-cad and PTPN-13 genes were decreased in HPV- positive samples while the expression level of SLUG, TWIST and N-cad was increased in HPV-positive samples compared to negative samples.

Conclusion: Our study suggests that HPV infection drives the induction of inflammation and EMT which may promote in the development of lung cancer.
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http://dx.doi.org/10.1186/s12885-020-07428-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7517685PMC
September 2020

Exosomal microRNAs: novel players in cervical cancer.

Epigenomics 2020 09 22;12(18):1651-1660. Epub 2020 Sep 22.

Research Center for Biochemistry & Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran.

Cervical cancer ranks fourth for both mortality and morbidity in women globally. Exosomes are considered as extracellular vesicles, secreted continuously by many cells with a size range from 30 to 150 nm. Exosomes can encapsulate microRNAs (miRNAs) and release them for cellular communications. This exosome-induced miRNA transfer is a novel strategy for genetic exchange among cells. This trafficking modality affects many pathological as well as physiological conditions. Moreover, exosomes can protect the miRNAs against harsh environments and keep them very stable. Given that a variety of exosomal miRNAs derived from cervical cancer cells can be targeted to recipient cells and contribute to tumorgenesis, it has been documented that exosomal miRNAs could be applied as diagnostic and therapeutic biomarkers in the treatment of cervical cancer. Herein, we summarize the pathologic and diagnostic roles of exosomal miRNAs in the cervical cancer. Moreover, we highlight the roles of exosomal miRNAs in other cancers.
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http://dx.doi.org/10.2217/epi-2020-0026DOI Listing
September 2020

The role of Epstein-Barr virus-expressed genes in breast cancer development.

Breast J 2020 11 11;26(11):2323-2326. Epub 2020 Sep 11.

Department of Microbiology, Faculty of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran.

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http://dx.doi.org/10.1111/tbj.14021DOI Listing
November 2020

The assessment of a possible link between HPV-mediated inflammation, apoptosis, and angiogenesis in Prostate cancer.

Int Immunopharmacol 2020 Nov 1;88:106913. Epub 2020 Sep 1.

Department of Virology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran. Electronic address:

Background: The aim of this study was to determine the presence of HPV in patients with Prostate cancer (PCa) and its possible association with cancer progression.

Methods: In this case-control study, fresh prostate tissues and blood samples were collected from 90 individuals, including 58 cases samples with PCa and 32 non-malignant prostate tissue samples as a control group. The expression level of viral genes (E2, E6, and E7) and cellular factors including tumor suppressor proteins (Rb and p53), anti-apoptotic mediators (Bcl-2 and survivin), and some mediators involved in inflammation and angiogenesis was evaluated.

Results: The presence of the HPV genome was identified in 19 out of the 58 cases (32.7%) and five out of the 32 controls (15.6%). However, there was not any statistically significant relationship between the presence of the HPV genome and PCa (OR = 2.63, 95% C.I = 0.89-7.91, P-value = 0.078). Moreover, the HPV high-risk genotypes 16 and 18 were detected in 47.4% and 31.6% of HPV-infected PCa tissues, respectively. The expression level of the tumor suppressor proteins (Rb and p53) significantly decreased in the HPV-infected samples compared to the HPV negative specimens (P-value = 0.01, P-value = 0.01, respectively). However, the expression level of the anti-apoptotic mediators and those involved in angiogenesis and inflammation significantly increased in the HPV-infected PCa group compared to the HPV-negative PCa and control groups (P-value < 0.05, respectively).

Conclusion: Our study suggests that although it is not definitely known whether HPV causes PCa, this virus probably modulates PCa cell behavior by affecting inflammation, angiogenesis, and apoptosis mechanisms, which, in turn, promotes tumorigenesis.
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http://dx.doi.org/10.1016/j.intimp.2020.106913DOI Listing
November 2020

Circular RNAs: New Epigenetic Signatures in Viral Infections.

Front Microbiol 2020 31;11:1853. Epub 2020 Jul 31.

Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran.

Covalent closed circular RNAs (circRNAs) can act as a bridge between non-coding RNAs and coding messenger RNAs. CircRNAs are generated by a back-splicing mechanism during post-transcriptional processing and are abundantly expressed in eukaryotic cells. CircRNAs can act via the modulation of RNA transcription and protein production, and by the sponging of microRNAs (miRNAs). CircRNAs are now thought to be involved in many different biological and pathological processes. Some studies have suggested that the expression of host circRNAs is dysregulated in several types of virus-infected cells, compared to control cells. It is highly likely that viruses can use these molecules for their own purposes. In addition, some viral genes are able to produce viral circRNAs (VcircRNA) by a back-splicing mechanism. However, the viral genes that encode VcircRNAs, and their functions, are poorly studied. In this review, we highlight some new findings about the interaction of host circRNAs and viral infection. Moreover, the potential of VcircRNAs derived from the virus itself, to act as biomarkers and therapeutic targets is summarized.
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http://dx.doi.org/10.3389/fmicb.2020.01853DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7412987PMC
July 2020

The assessment of selected MiRNAs profile in HIV, HBV, HCV, HIV/HCV, HIV/HBV Co-infection and elite controllers for determination of biomarker.

Microb Pathog 2020 Oct 20;147:104355. Epub 2020 Jun 20.

Department of Microbiology, Faculty of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran. Electronic address:

Background: The emerging relationship between microRNAs (miRNA) and viral-control is a topic of interest in the field of HIV. Host-genome might play an important role in the control of viremia. The aim of this study was to assess the specific miRNA profile that could contribute to the control of HIV replication in Elite Controllers.

Materials And Methods: The expression level of miRNAs was evaluated in 6 group patients, Elite Controller (EC), HIV, HBV, HCV, HIV-HBV-HIV-HCV, and healthy controls using real-time PCR assays. Also, liver enzymes (ALT and AST) and CD4 T cell count was assessed.

Results: After adequate normalization, expression level of miRNAs was determined. The expression level of miR-146 in HIV/HCV co-infected patients was the highest in all groups. The miRNAs expression profile was significantly different in patient groups compared to control and EC. Some miRNA was significantly correlated with viral load and CD4 T cell count.

Conclusions: The involvement of the mentioned miRNAs and correlation of these with viral and cellular parameters can justify the clinical outcome of all patient groups. The differentially expressed miRNA profile in patients suggests that miRNAs can be serve as biomarkers for risk of disease progression and differentiation of infections. Moreover, determining the profiles of miRNAs due to involvement of these in the pathogenesis of infection and manipulating these miRNAs could lead to opening a new gate to infection control.
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http://dx.doi.org/10.1016/j.micpath.2020.104355DOI Listing
October 2020

Association between Parvovirus B19 and anemia in HIV-infected patients.

Med J Islam Repub Iran 2019 16;33:137. Epub 2019 Dec 16.

Department of Microbiology, Faculty of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Human parvovirus B19 (B19V) can cause anemia in some patients, including those with compromised immunity system. There are a few studies on molecular epidemiology of B19V and its association with anemia in Iran. Therefore, the aim of this study was to determine the B19V DNA, IgM, IgG, genotyping, and viral load in HIV patients in different groups of pregnant women, general population, injection drug users (IDU), and Elite controllers. Also, the possible association of B19V with anemia was studied. In this case-control study, B19V DNA, anti-B19V IgM, anti-B19V IgG, viral load, and hemoglobin level were assessed in 113 HIV positive patients and 72 healthy controls. Also, CD4+ T cell counts and HIV load were measured in the patients' group. All statistical analyses were done using STATA 14.2 software (Stata Corporation, College Station, Texas, USA). P value < 0.05 was considered statistically significant. Among HIV patients, 19 (16.8%) cases had B19V DNA, 3 (2.7%) had B19V IgM, and 7 (6.2%) had B19V IgG. In control group, the prevalence of B19V DNA, IgM, and IgG was 6 (8.33%), 7(9.7%), and 19 (26.4%), respectively. In subpopulations based on transmission routes, general population had the highest B19V IgG and DNA positivity prevalence and viral load level. There was no significant association between B19V antibodies and DNA with anemia. The results demonstrated that B19V infection cannot be considered as a high-risk factor for anemia in adult HIV patients. However, further studies are needed to determine the exact role of B19V infection in HIV patients.
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http://dx.doi.org/10.34171/mjiri.33.137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7137816PMC
December 2019

Viral infections and risk of thyroid cancer: A systematic review and empirical bayesian meta-analysis.

Pathol Res Pract 2020 Apr 13;216(4):152855. Epub 2020 Feb 13.

Department of Microbiology, Faculty of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran. Electronic address:

Objective: The associations between viruses and the cancer have been conducted in several studies while there has been no systematic review and meta-analysis about the association between viral infections and thyroid cancer (TC). Therefore, we investigated the association between viral infection and TC risk.

Methods: Systematic search was done from 1994 to 2019 in Web of sciences (ISI), PubMed, and Scopus databases. Pooled logarithm of odds ratio (OR) and their corresponding 95 % confidence interval (CI) and pooled prevalence of viral infections were calculated to find the association between the viral infections and TC risk and overall prevalence of the viral infections in TC.

Results: Twenty-three of 852 original articles were selected and included in the study. According to the results of the random effect meta-analysis, the pooled prevalence of viral infections in the TC patients was 37 % (95 % C. I = 22 %-55 %). In addition, there was a significant association between viral infections (log (OR) = 1.51, 95 % credible interval = 0.68-2.39) and TC risk. The highest associations were observed between TC risk and Simian Vacuolating Virus 40 (SV40) and B19 infections, respectively. The lowest non-significant association was found between TC risk and Poliovirus type 1 infection. The significantly heterogeneity was observed between included studies (Q test: p-value<0.001; I = 73.82 %; τ = 1.08, 95 % Cr. I = 0.47-1.94).

Conclusions: Results clearly demonstrated the potential pathogenetic association between viral infections and increased risk of TC.
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http://dx.doi.org/10.1016/j.prp.2020.152855DOI Listing
April 2020

Exosomal miRNAs: novel players in viral infection.

Epigenomics 2020 02 25;12(4):353-370. Epub 2020 Feb 25.

Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, 40 Blossom Street, Boston, MA 02114, USA.

Exosomes are secreted nanovesicles that are able to transfer their cargo (such as miRNAs) between cells. To determine to what extent exosomes and exosomal miRNAs are involved in the pathogenesis, progression and diagnosis of viral infections. The scientific literature (PubMed and Google Scholar) was searched from 1970 to 2019. The complex biogenesis of exosomes and miRNAs was reviewed. Exosomes contain both viral and host miRNAs that can be used as diagnostic biomarkers for viral diseases. Viral proteins can alter miRNAs, and conversely miRNAs can alter the host response to viral infections in a positive or negative manner. It is expected that exosomal miRNAs will be increasingly used for diagnosis, monitoring and even treatment of viral infections.
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http://dx.doi.org/10.2217/epi-2019-0192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713899PMC
February 2020

Exosomes and Lung Cancer: Roles in Pathophysiology, Diagnosis and Therapeutic Applications.

Curr Med Chem 2021 ;28(2):308-328

Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, 40 Blossom Street, Boston, MA, 02114, United States.

Lung cancer is a malignancy with a high morbidity and mortality rate, and affected patients have low survival and poor prognosis. The therapeutic approaches for the treatment of this cancer, including radiotherapy and chemotherapy, are not particularly effective partly due to late diagnosis. Therefore, the search for new diagnostic and prognostic tools is a critical issue. Novel biomarkers, such as exosomes, could be considered as potential diagnostic tools for malignancies, particularly lung cancer. Exosomes are nanovesicles, which are associated with different physiological and pathological conditions. It has been shown that these particles are released from many cells, such as cancer cells, immune cells and to some degree normal cells. Exosomes could alter the behavior of target cells through intercellular transfer of their cargo (e.g. DNA, mRNA, long non-coding RNAs, microRNAs and proteins). Thus, these vehicles may play pivotal roles in various physiological and pathological conditions. The current insights into lung cancer pathogenesis suggest that exosomes are key players in the pathogenesis of this cancer. Hence, these nanovesicles and their cargos could be used as new diagnostic, prognostic and therapeutic biomarkers in the treatment of lung cancer. Besides the diagnostic roles of exosomes, their use as drug delivery systems and as cancer vaccines is under investigation. The present review summarizes the current information on the diagnostic and pathogenic functions of exosomes in lung cancer.
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http://dx.doi.org/10.2174/0929867327666200204141952DOI Listing
February 2021

The role of miR-146a in viral infection.

IUBMB Life 2020 03 30;72(3):343-360. Epub 2019 Dec 30.

Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran.

Cellular microRNAs (miRNAs) were identified as a key player in the posttranscriptional regulation of cellular-genes regulatory pathways. They also emerged as a significant regulator of the immune response. In particular, miR-146a acts as an importance modulator of function and differentiation cells of the innate and adaptive immunity. It has been associated with disorder including cancer and viral infections. Given its significance in the regulation of key cellular processes, it is not surprising which virus infection have found ways to dysregulation of miRNAs. miR-146a has been identified in exosomes (exosomal miR-146a). After the exosomes release from donor cells, they are taken up by the recipient cell and probably the exosomal miR-146a is able to modulate the antiviral response in the recipient cell and result in making them more susceptible to virus infection. In this review, we discuss recent reports regarding miR-146a expression levels, target genes, function, and contributing role in the pathogenesis of the viral infection and provide a clue to develop the new therapeutic and preventive strategies for viral disease in the future.
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http://dx.doi.org/10.1002/iub.2222DOI Listing
March 2020

Evaluation of CCR5-Δ32 mutation among individuals with high risk behaviors, neonates born to HIV-1 infected mothers, HIV-1 infected individuals, and healthy people in an Iranian population.

J Med Virol 2020 08 17;92(8):1158-1164. Epub 2020 Jan 17.

Research Center of Pediatric Infectious Diseases, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran.

One of the important genetic factors related to resistance to HIV-1 infection is the presence of the C-C chemokine receptor type 5 delta 32 (CCR5-Δ32) homozygous genotype (Δ32/Δ32). The aim of this study was to evaluate the CCR5-Δ32 mutation among individuals with high-risk behaviors, neonates born to HIV-1-infected mothers in the prevention of mother-to-child transmission (PMTCT) project, HIV-1-infected individuals, and healthy people. The frequency of the CCR5-Δ32 genotype was assessed in a cross-sectional survey carried out from March 2014 to March 2019 among four different groups of the Iranian population. Genomic DNA was extracted from peripheral blood mononuclear cells of 140 Iranian healthy people, 84 neonates born to HIV-1-infected mothers in the PMTCT project, 71 people with high-risk behaviors, and 76 HIV-1-infected individuals. The polymerase chain reaction method was used for the amplification of the CCR5 gene. The CCR5-Δ32 heterozygous deletion was detected in five (6.6%) HIV-1-infected individuals, four (4.7%) neonates born to HIV-1 positive mothers, two (1.4%) healthy people, and also three (4.2%) people with high-risk behaviors whereas the CCR5-Δ32 homozygous deletion was absent in all the groups (Fisher's exact test, P = .0242). The allele of CCR5-Δ32 homozygous was not detected in the four study groups, and no significant difference was seen in the frequency of the CCR5Δ32 heterozygous allele between HIV seropositive and seronegative individuals. Therefore, it seems that this allele alone cannot explain the natural resistance to HIV-1 infection and probably several mechanisms are responsible for these processes and it should be further investigated.
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http://dx.doi.org/10.1002/jmv.25658DOI Listing
August 2020

Pathogenic role of exosomes and microRNAs in HPV-mediated inflammation and cervical cancer: A review.

Int J Cancer 2020 01 31;146(2):305-320. Epub 2019 Oct 31.

Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA.

Cervical cancer (CC) is the fourth most common cause of cancer death in women. The most important risk factor for the development of CC is cervical infection with human papilloma virus (HPV). Inflammation is a protective strategy that is triggered by the host against pathogens such as viral infections that acts rapidly to activate the innate immune response. Inflammation is beneficial if it is brief and well controlled; however, if the inflammation is excessive or it becomes of chronic duration, it can produce detrimental effects. HPV proteins are involved, both directly and indirectly, in the development of chronic inflammation, which is a causal factor in the development of CC. However, other factors may also have a potential role in stimulating chronic inflammation. MicroRNAs (miRNAs) (a class of noncoding RNAs) are strong regulators of gene expression. They have emerged as key players in several biological processes, including inflammatory pathways. Abnormal expression of miRNAs may be linked to the induction of inflammation that occurs in CC. Exosomes are a subset of extracellular vesicles shed by almost all types of cells, which can function as cargo transfer vehicles. Exosomes contain proteins and genetic material (including miRNAs) derived from their parent cells and can potentially affect recipient cells. Exosomes have recently been recognized to be involved in inflammatory processes and can also affect the immune response. In this review, we discuss the role of HPV proteins, miRNAs and exosomes in the inflammation associated with CC.
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http://dx.doi.org/10.1002/ijc.32688DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6999596PMC
January 2020

microRNAs: New prognostic, diagnostic, and therapeutic biomarkers in cervical cancer.

J Cell Physiol 2019 08 19;234(10):17064-17099. Epub 2019 Mar 19.

Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran.

Cervical cancer is as a kind of cancer beginning from the cervix. Given that cervical cancer could be observed in women who infected with papillomavirus, regular oral contraceptives, and multiple pregnancies. Early detection of cervical cancer is one of the most important aspects of the therapy of this malignancy. Despite several efforts, finding and developing new biomarkers for cervical cancer diagnosis are required. Among various prognostic, diagnostic, and therapeutic biomarkers, miRNA have been emerged as powerful biomarkers for detection, treatment, and monitoring of response to therapy in cervical cancer. Here, we summarized various miRNAs as an employable platform for prognostic, diagnostic, and therapeutic biomarkers in the treatment of cervical cancer.
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http://dx.doi.org/10.1002/jcp.28457DOI Listing
August 2019

Association between human papillomavirus infection and prostate cancer: A global systematic review and meta-analysis.

Asia Pac J Clin Oncol 2019 Oct 10;15(5):e59-e67. Epub 2019 Feb 10.

Department of Virology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Although an increasing number of studies have been conducted to evaluate the association between human papillomavirus (HPV) infections and distribution of HPV types worldwide with the risk of prostate cancer (PC), the results remain inadequate. Hence, we investigated the association between HPV infection and PC risk using a meta-analysis. Relevant studies from January 1990 to December 2016 were searched in PubMed, Web of sciences, and Scopus databases. Pooled odds ratio (OR) and their corresponding 95% confidence interval (CI) were calculated to find the association between the prevalence of HPV and prostate cancer risk. To do so, data from 24 studies with 5546 prostate cancer cases were pooled in order to evaluate the heterogeneity of chief parameters including study region, specimen type, HPV DNA source, detection technique, publication calendar period, and Gleason score. All statistical analyses were performed using STATA 11 and MedCalc 13. A significant positive association was found between HPV infection and PC risk (OR = 1.281; P = 0.026). The genotype 16 was more frequently found in patients with PC which significantly increased the cancer risk (OR = 1.60; P < 0.001). Age 65 and older could significantly escalate PC risk (OR = 3.564; P < 0.001). Our results clearly favor the potential pathogenetic link between HPV infection and increased risk of PC affirming that HPV infections could play a part in the risk of PC.
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http://dx.doi.org/10.1111/ajco.13124DOI Listing
October 2019

microRNAs: Key players in virus-associated hepatocellular carcinoma.

J Cell Physiol 2019 08 7;234(8):12188-12225. Epub 2018 Dec 7.

Department of Virology, Iran University of Medical Sciences, Tehran, Iran.

Hepatocellular carcinoma (HCC) is known as one of the major health problems worldwide. Pathological analysis indicated that a variety of risk factors including genetical (i.e., alteration of tumor suppressors and oncogenes) and environmental factors (i.e., viruses) are involved in beginning and development of HCC. The understanding of these risk factors could guide scientists and clinicians to design effective therapeutic options in HCC treatment. Various viruses such as hepatitis B virus (HBV) and hepatitis C virus (HCV) via targeting several cellular and molecular pathways involved in HCC pathogenesis. Among various cellular and molecular targets, microRNAs (miRNAs) have appeared as key players in HCC progression. miRNAs are short noncoding RNAs which could play important roles as oncogenes or tumor suppressors in several malignancies such as HCC. Deregulation of many miRNAs (i.e., miR-222, miR-25, miR-92a, miR-1, let-7f, and miR-21) could be associated with different stages of HCC. Besides miRNAs, exosomes are other particles which are involved in HCC pathogenesis via targeting different cargos, such as DNAs, RNAs, miRNAs, and proteins. In this review, we summarize the current knowledge of the role of miRNAs and exosomes as important players in HCC pathogenesis. Moreover, we highlighted HCV- and HBV-related miRNAs which led to HCC progression.
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http://dx.doi.org/10.1002/jcp.27956DOI Listing
August 2019

Influenza vaccine: Where are we and where do we go?

Rev Med Virol 2019 01 8;29(1):e2014. Epub 2018 Nov 8.

Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

The alarming rise of morbidity and mortality caused by influenza pandemics and epidemics has drawn attention worldwide since the last few decades. This life-threatening problem necessitates the development of a safe and effective vaccine to protect against incoming pandemics. The currently available flu vaccines rely on inactivated viral particles, M2e-based vaccine, live attenuated influenza vaccine (LAIV) and virus like particle (VLP). While inactivated vaccines can only induce systemic humoral responses, LAIV and VLP vaccines stimulate both humoral and cellular immune responses. Yet, these vaccines have limited protection against newly emerging viral strains. These strains, however, can be targeted by universal vaccines consisting of conserved viral proteins such as M2e and capable of inducing cross-reactive immune response. The lack of viral genome in VLP and M2e-based vaccines addresses safety concern associated with existing attenuated vaccines. With the emergence of new recombinant viral strains each year, additional effort towards developing improved universal vaccine is warranted. Besides various types of vaccines, microRNA and exosome-based vaccines have been emerged as new types of influenza vaccines which are associated with new and effective properties. Hence, development of a new generation of vaccines could contribute to better treatment of influenza.
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http://dx.doi.org/10.1002/rmv.2014DOI Listing
January 2019

Epstein-Barr virus and thyroid cancer: The role of viral expressed proteins.

J Cell Physiol 2019 04 26;234(4):3790-3799. Epub 2018 Oct 26.

Department of Internal Medicine, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Background: Thyroid cancer is a common endocrine malignancy whose incidence has increased in recent years. Several internal and external risk factors are involved in the development of this cancer, such as infectious agents. Evidence supporting the role of viral infection as an etiology for the invasiveness of thyroid cancer is increasing. The aim of this study was to determine the presence of the Epstein-Barr virus (EBV) and the association between viral gene products and thyroid tumor development.

Methods: Fifty-seven thyroid cancer specimens were collected from the same number of patients as well as 18 samples from healthy controls. The presence of the EBV genome and the genotyping was examined by polymerase chain reaction (PCR). Also, an enzyme-linked immunosorbent assay and real-time PCR were used to measure the expression levels of viral and cellular genes.

Results: The EBV DNA was detected in 71.9% of the samples, and it was also found that the presence of the EBV was associated with increasing development of thyroid tumor.

Conclusion: Our results demonstrated that EBV infection may play a role in the development of thyroid tumor.
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http://dx.doi.org/10.1002/jcp.27144DOI Listing
April 2019

Genetic and epigenetic contribution to astrocytic gliomas pathogenesis.

J Neurochem 2019 01 3;148(2):188-203. Epub 2018 Dec 3.

Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran.

Astrocytic gliomas are the most common and lethal form of intracranial tumors. These tumors are characterized by a significant heterogeneity in terms of cytopathological, transcriptional, and (epi)genomic features. This heterogeneity has made these cancers one of the most challenging types of cancers to study and treat. To uncover these complexities and to have better understanding of the disease initiation and progression, identification, and characterization of underlying cellular and molecular pathways related to (epi)genetics of astrocytic gliomas is crucial. Here, we discuss and summarize molecular and (epi)genetic mechanisms that provide clues as to the pathogenesis of astrocytic gliomas.
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http://dx.doi.org/10.1111/jnc.14616DOI Listing
January 2019

miRNA-based strategy for modulation of influenza A virus infection.

Epigenomics 2018 06 11;10(6):829-844. Epub 2018 Jun 11.

Department of Biomaterials, Tissue Engineering & Nanotechnology, School of Advanced Technologies in Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

Influenza A virus is known worldwide as a threat associated with human and livestock diseases. Hence, identification of physiological and molecular aspects of influenza A could contribute to better design of therapeutic approaches for reducing adverse effects associated with disease caused by this virus. miRNAs are epigenetic regulators playing important roles in many pathological processes that help in progression of influenza A. Besides miRNAs, exosomes have ememrged as other effective players in influenza A pathogenesis. Exosomes exert their effects via targeting their cargos (e.g., DNAs, mRNA, miRNAs and proteins) to recipient cells. Here, we summarized various roles of miRNAs and exosomes in influenza A pathogenesis. Moreover, we highlighted therapeutic applications of miRNAs and exosomes in influenza.
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http://dx.doi.org/10.2217/epi-2017-0170DOI Listing
June 2018
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