Publications by authors named "Sajad Karampoor"

36 Publications

A possible pathogenic correlation between neutrophil elastase (NE) enzyme and inflammation in the pathogenesis of coronavirus disease 2019 (COVID-19).

Int Immunopharmacol 2021 Sep 14;100:108137. Epub 2021 Sep 14.

Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran; Department of Virology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran. Electronic address:

A growing body of evidence indicates that neutrophil elastase (NE) is involved in the pathogenesis of respiratory infectious diseases, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study aimed to analyze the dynamic changes in serum levels of NE associated with inflammation, disease activity, and mortality rate in patients with COVID-19. We measured the serum concentrations of NE, C-Reactive protein (CRP), interleukin (IL)- 4, IL-6, IL-8, IL-10, and vitamin D levels in 83 ICU and 69 non-ICU patients compared with 82 healthy subjects (HS) in three-time points (T1-T3). Serum levels of NE, IL-6, IL-8, and CRP in ICU and non-ICU patients were significantly higher than HS (P < 0.001) in three-time points. Also, serum levels of NE, IL-6, IL-8, and CRP in ICU patients were significantly higher than in non-ICU patients (P < 0.05). On the day of admission (T1), the levels of NE, CRP, IL-6, IL-8 were gradually decreased from T1 to T3. At the same time, IL-4 and IL-10 were gradually increased from T1 to T2 and then reduced to T3. Further analyses demonstrated that the levels of NE, IL-6, and IL-8 in deceased patients were significantly higher than in recovered patients (P < 0.05). The ROC curve analysis demonstrated that markers, including NE, IL-6, and IL-8, were valuable indicators in evaluating the activity of COVID-19. Overall, our results signify the critical role of NE in the pathogenesis of COVID-19, and also, further support that NE has a potential therapeutic target for the attenuation of COVID-19 severity.
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http://dx.doi.org/10.1016/j.intimp.2021.108137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8437823PMC
September 2021

Persistent hiccups after treatment of COVID-19 with dexamethasone: A case report.

Respir Med Case Rep 2021 10;34:101515. Epub 2021 Sep 10.

Department of Infectious Diseases, Firoozgar Medical and Educational Hospital, Iran University of Medical Sciences, Tehran, Iran.

Hiccups are involuntary and spasmodic contractions of the diaphragm, and multiple etiological factors have been suggested to be involved. Medications, such as dexamethasone, as well as some diseases, such as pneumonia, can cause persistent (>48 h) hiccups. Here, we report a 58-years-old male who had a fever, myalgia, cough, and ground-glass view in the chest computed tomography, and his PCR test for Covid-19 was positive. During the treatment course, persistent hiccups were developed after taking dexamethasone and lasted for six days. All cardiac and neurologic examinations were performed, and all of them were normal. After evaluating all of the possible underlying causes, dexamethasone was replaced by prednisolone. Upon a change in his treatment regimen, hiccups began to stop, and his symptoms also disappeared. Hiccups may occur in patients who have pneumonia and other infectious diseases. Dexamethasone can also stimulate hiccups along with infections.
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http://dx.doi.org/10.1016/j.rmcr.2021.101515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8431841PMC
September 2021

microRNAs in human brucellosis: A promising therapeutic approach and biomarker for diagnosis and treatment.

Immun Inflamm Dis 2021 Aug 27. Epub 2021 Aug 27.

Department of Microbiology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.

Introduction: Human brucellosis is a zoonotic bacterial disease with up to 500,000 new cases each year. The major evasion mechanisms from the host immune system by Brucella are restraint of complement pathway and Toll-like receptors signaling pathways, interference with efficient antigen presentation to CD4-positive T lymphocytes, selective subversion of autophagy pathways, inhibition of dendritic cell stimulation, inhibition of autophagolysosomal fusion, and macrophage apoptosis. Many molecular and cellular pathways contribute to brucellosis that microRNAs have a vital function in the immunopathogenesis of this disease. In this regard, these molecules apply for their roles by modulating various events like inflammatory reactions and immune defense. Recently, in the case of immunity to human brucellosis, it has been shown that microRNAs play an important role in immunity against these bacteria.

Methods And Results: In this study, we tried to review the immune defense and immunopathogenesis of Brucella infection and highlight the current knowledge of the microRNAs in infected cells by Brucella pathogens. The recent findings suggest that the regulation of microRNAs expression is impaired during brucellosis infection, which may contribute to disease progression or inhibition by modulating immune responses against this pathogen.

Conclusions: The interplay between miRNAs and Brucella pathogens and the underlying process required comprehensive examination to unravel the novel therapeutic or diagnostic approaches.
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http://dx.doi.org/10.1002/iid3.519DOI Listing
August 2021

Immunometabolism in human brucellosis: An emerging field of investigation.

Microb Pathog 2021 Sep 28;158:105115. Epub 2021 Jul 28.

Department of Microbiology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran; Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran. Electronic address:

In recent years, extreme attention has been focused on the role of immunometabolism in the regulation of immune cell responses in healthy individuals during infection, autoimmunity, and cancer. In the infection biology area, it has been shown that there is a close relationship between the immune system and the host metabolic changes. Brucella species is an intracellular coccobacillus that infects humans and mammals, which led to brucellosis. Brucella species with host-specific evolutionary mechanisms allow it to hide from or manipulate cellular immunity and achieve intracellular persistence. Intracellular bacterial pathogens such as Brucella species also employ host cell resources to replicate and persist inside the host. Targeting these host systems is one promising strategy for developing novel antimicrobials to tackle intracellular infections. This study will summarize the role of metabolic reprogramming in immune cells and their relationship to brucellosis.
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http://dx.doi.org/10.1016/j.micpath.2021.105115DOI Listing
September 2021

Role of microbiota-derived short-chain fatty acids in nervous system disorders.

Biomed Pharmacother 2021 Jul 8;139:111661. Epub 2021 May 8.

Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran; Department of Virology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran. Electronic address:

During the past decade, accumulating evidence from the research highlights the suggested effects of bacterial communities of the human gut microbiota and their metabolites on health and disease. In this regard, microbiota-derived metabolites and their receptors, beyond the immune system, maintain metabolism homeostasis, which is essential to maintain the host's health by balancing the utilization and intake of nutrients. It has been shown that gut bacterial dysbiosis can cause pathology and altered bacterial metabolites' formation, resulting in dysregulation of the immune system and metabolism. The short-chain fatty acids (SCFAs), such as butyrate, acetate, and succinate, are produced due to the fermentation process of bacteria in the gut. It has been noted remodeling in the gut microbiota metabolites associated with the pathophysiology of several neurological disorders, such as Alzheimer's disease, multiple sclerosis, Parkinson's disease, amyotrophic lateral sclerosis, stress, anxiety, depression, autism, vascular dementia, schizophrenia, stroke, and neuromyelitis optica spectrum disorders, among others. This review will discuss the current evidence from the most significant studies dealing with some SCFAs from gut microbial metabolism with selected neurological disorders.
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http://dx.doi.org/10.1016/j.biopha.2021.111661DOI Listing
July 2021

The pathogenic, therapeutic and diagnostic role of exosomal microRNA in the autoimmune diseases.

J Neuroimmunol 2021 Sep 24;358:577640. Epub 2021 Jun 24.

Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran; Department of Virology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran. Electronic address:

Exosomes are a nano-vesicle surrounded by a bilipid layer that can release from almost all cells and could be detected in tissues and biological liquids. These vesicles contain lipids, proteins, and nucleic acids (including DNA, mRNA, and miRNA) inside and on the exosomes' surface constitute their content. Exosomes can transfer their cargo into the recipient cell, which can modify recipient cells' biological activities. Recently it has been deciphering that the miRNA pattern of exosomes reveals the cellular pathophysiological situation and modifies various biological processes. Increasing data regarding exosomes highlights that the exosomes and their cargo, especially miRNAs, are implicated in the pathophysiology of various disorders, such as autoimmune disease. The current evidence on the deciphering of mechanisms in which exosomal miRNAs contributed to autoimmunity was indicated that exosomal miRNA might hold information that can reprogram the function of many of the immune cells involved in autoimmune diseases' pathogenesis. In the present study, we summarized the pathogenic role of exosomal miRNAs in several autoimmune diseases, including myasthenia gravis (MG), psoriasis, inflammatory bowel disease (IBD), type 1 diabetes (T1D), multiple sclerosis (MS), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjogren's Syndrome (SS), systemic sclerosis (SSc), vitiligo, and autoimmune thyroid diseases (AITD). Moreover, in this work, we present evidence of the potential role of exosomal miRNAs as therapeutic and diagnostic agents in autoimmune diseases.
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http://dx.doi.org/10.1016/j.jneuroim.2021.577640DOI Listing
September 2021

A possible pathogenic role of Syndecan-1 in the pathogenesis of coronavirus disease 2019 (COVID-19).

Int Immunopharmacol 2021 Aug 17;97:107684. Epub 2021 Apr 17.

Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran; Department of Virology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran. Electronic address:

A cell-surface heparan proteoglycan called Syndecan-1 (SDC-1) has multiple roles in healthy and pathogenic conditions, including respiratory viral infection. In this study, we explore the dynamic alternation in the levels of SDC-1 in cases with COVID-19. A total of 120 cases definitely diagnosed with COVID-19 were admitted to the Firoozgar Hospital, Tehran, Iran, from December 1, 2020, to January 29, 2021, and included in our study. Also, 58 healthy subjects (HS) were chosen as the control group. Patients were classified into two groups: 1) ICU patients and (63 cases) 2) non-ICU patients (57 cases). The dynamic changes of serum SCD-1, CRP, IL-6, IL-10, IL-18, and Vit D levels a well as the disease activity were investigated in three-time points (T1-T3). Our results indicated that the COVID-19 patients had significantly increased SCD-1, CRP, IL-6, IL-10, and IL-18 levels than in HS, while the Vit D levels in COVID-19 patients were significantly lower than HS. Further analysis demonstrated that the SCD-1, CRP, IL-6, IL-10, and IL-18 levels in ICU patients were significantly higher than in non-ICU patients. Tracking dynamic changes in the above markers indicated that on the day of admission, the SCD-1, CRP, IL-6, IL-10, and IL-18 levels were gradually increased on day 5 (T2) and then gradually decreased on day 10 (T3). ROC curve analysis suggests that markers mentioned above, SDC-1, IL-6, and IL-18 are valuable indicators in evaluating the activity of COVID-19. All in all, it seems that the serum SDC-1 levels alone or combined with other markers might be a good candidate for disease activity monitoring.
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http://dx.doi.org/10.1016/j.intimp.2021.107684DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052477PMC
August 2021

Role of microbiota-derived short-chain fatty acids in cancer development and prevention.

Biomed Pharmacother 2021 Jul 24;139:111619. Epub 2021 Apr 24.

Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran; Department of Virology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran. Electronic address:

Following cancer, cells in a particular tissue can no longer respond to the factors involved in controlling cell survival, differentiation, proliferation, and death. In recent years, it has been indicated that alterations in the gut microbiota components, intestinal epithelium, and host immune system are associated with cancer incidence. Also, it has been demonstrated that the short-chain fatty acids (SCFAs) generated by gut microbiota are vitally crucial in cell homeostasis as they contribute to the modulation of histone deacetylases (HDACs), resulting effected cell attachment, immune cell immigration, cytokine production, chemotaxis, and the programmed cell death. Therefore, the manipulation of SCFA levels in the intestinal tract by alterations in the microbiota structure can be potentially taken into consideration for cancer treatment/prevention. In the current study, we will explain the most recent findings on the detrimental or protective roles of SFCA (particularly butyrate, propionate, and acetate) in several cancers, including bladder, colon, breast, stomach, liver, lung, pancreas, and prostate cancers.
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http://dx.doi.org/10.1016/j.biopha.2021.111619DOI Listing
July 2021

The emerging role of exosomal miRNAs as a diagnostic and therapeutic biomarker in Mycobacterium tuberculosis infection.

Mol Med 2021 04 1;27(1):34. Epub 2021 Apr 1.

Department of Microbiology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), has been the world's driving fatal bacterial contagious disease globally. It continues a public health emergency, and around one-third of the global community has been affected by latent TB infection (LTBI). This is mostly due to the difficulty in diagnosing and treating patients with TB and LTBI. Exosomes are nanovesicles (40-100 nm) released from different cell types, containing proteins, lipids, mRNA, and miRNA, and they allow the transfer of one's cargo to other cells. The functional and diagnostic potential of exosomal miRNAs has been demonstrated in bacterial infections, including TB. Besides, it has been recognized that cells infected by intracellular pathogens such as Mtb can be secreting an exosome, which is implicated in the infection's fate. Exosomes, therefore, open a unique viewpoint on the investigative process of TB pathogenicity. This study explores the possible function of exosomal miRNAs as a diagnostic biomarker. Moreover, we include the latest data on the pathogenic and therapeutic role of exosomal miRNAs in TB.
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http://dx.doi.org/10.1186/s10020-021-00296-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017856PMC
April 2021

The emerging role of probiotics as a mitigation strategy against coronavirus disease 2019 (COVID-19).

Arch Virol 2021 Jul 20;166(7):1819-1840. Epub 2021 Mar 20.

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

COVID-19 is an acute respiratory infection accompanied by pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has affected millions of people globally. To date, there are no highly efficient therapies for this infection. Probiotic bacteria can interact with the gut microbiome to strengthen the immune system, enhance immune responses, and induce appropriate immune signaling pathways. Several probiotics have been confirmed to reduce the duration of bacterial or viral infections. Immune fitness may be one of the approaches by which protection against viral infections can be reinforced. In general, prevention is more efficient than therapy in fighting viral infections. Thus, probiotics have emerged as suitable candidates for controlling these infections. During the COVID-19 pandemic, any approach with the capacity to induce mucosal and systemic reactions could potentially be useful. Here, we summarize findings regarding the effectiveness of various probiotics for preventing virus-induced respiratory infectious diseases, especially those that could be employed for COVID-19 patients. However, the benefits of probiotics are strain-specific, and it is necessary to identify the bacterial strains that are scientifically established to be beneficial.
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http://dx.doi.org/10.1007/s00705-021-05036-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7980799PMC
July 2021

The emerging role of microRNAs in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Int Immunopharmacol 2021 Jan 13;90:107204. Epub 2020 Nov 13.

Department of Virology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran; Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran. Electronic address:

The novel coronavirus disease 2019 (COVID-19) pandemic has imposed significant public health problems for the human populations worldwide after the 1918 influenza A virus (IVA) (H1N1) pandemic. Although numerous efforts have been made to unravel the mechanisms underlying the coronavirus, a notable gap remains in our perception of the COVID-19 pathogenesis. The innate and adaptive immune systems have a pivotal role in the fate of viral infections, such as COVID-19 pandemic. MicroRNAs (miRNAs) are known as short noncoding RNA molecules and appear as indispensable governors of almost any cellular means. Several lines of evidence demonstrate that miRNAs participate in essential mechanisms of cell biology, regulation of the immune system, and the onset and progression of numerous types of disorders. The immune responses to viral respiratory infections (VRIs), including influenza virus (IV), respiratory syncytial virus (RSV), and rhinovirus (RV), are correlated with the ectopic expression of miRNAs. Alterations of the miRNA expression in epithelial cells may contribute to the pathogenesis of chronic and acute airway infections. Hence, analyzing the role of these types of nucleotides in antiviral immune responses and the characterization of miRNA target genes might contribute to understanding the mechanisms of the interplay between the host and viruses, and in the future, potentially result in discovering therapeutic strategies for the prevention and treatment of acute COVID-19 infection. In this article, we present a general review of current studies concerning the function of miRNAs in different VRIs, particularly in coronavirus infection, and address all available therapeutic prospects to mitigate the burden of viral infections.
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http://dx.doi.org/10.1016/j.intimp.2020.107204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7664359PMC
January 2021

Overview of the current promising approaches for the development of an effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine.

Int Immunopharmacol 2020 Nov 24;88:106928. Epub 2020 Aug 24.

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

Coronavirus disease 2019 (COVID-19) is a pandemic infectious disease caused by the novel coronavirus called SARS-CoV-2. There is a gap in our understanding regarding the immunopathogenesis of COVID-19. However, many clinical trials are underway across the world for screening effective drugs against COVID-19. Nevertheless, currently, no proven effective therapies for this virus exists. The vaccines are deemed as a significant part of disease prevention for emerging viral diseases, since, in several cases, other therapeutic choices are limited or non-existent, or that diseases result in such an accelerated clinical worsening that the efficacy of treatments is restricted. Therefore, effective vaccines against COVID-19 are urgently required to overcome the tremendous burden of mortality and morbidity correlated with SARS-CoV-2. In this review, we will describe the latest evidence regarding outstanding vaccine approaches and the challenges for vaccine production.
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http://dx.doi.org/10.1016/j.intimp.2020.106928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7444935PMC
November 2020

Corrigendum to "HIV-1 Tat protein attenuates the clinical course of experimental autoimmune encephalomyelitis (EAE)" [Int. Immunopharmacol. 78 (2020) 105943].

Int Immunopharmacol 2020 Nov 14;88:106742. Epub 2020 Aug 14.

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

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http://dx.doi.org/10.1016/j.intimp.2020.106742DOI Listing
November 2020

Coronavirus disease 2019 (COVID-19): Immunological approaches and emerging pharmacologic treatments.

Int Immunopharmacol 2020 Nov 8;88:106885. Epub 2020 Aug 8.

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

The SARS-CoV-2 virus is an etiological agent of pandemic COVID-19, which spreads rapidly worldwide. No proven effective therapies currently exist for this virus, and efforts to develop antiviral strategies for the treatment of COVID-19 are underway. The rapidly increasing understanding of SARS-CoV-2 virology provides a notable number of possible immunological procedures and drug targets. However, gaps remain in our understanding of the pathogenesis of COVID-19. In this review, we describe the latest information in the context of immunological approaches and emerging current antiviral strategies for COVID-19 treatment.
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http://dx.doi.org/10.1016/j.intimp.2020.106885DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7414363PMC
November 2020

Bacterial co-infections with SARS-CoV-2.

IUBMB Life 2020 10 8;72(10):2097-2111. Epub 2020 Aug 8.

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

The pandemic coronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has affected millions of people worldwide. To date, there are no proven effective therapies for this virus. Efforts made to develop antiviral strategies for the treatment of COVID-19 are underway. Respiratory viral infections, such as influenza, predispose patients to co-infections and these lead to increased disease severity and mortality. Numerous types of antibiotics such as azithromycin have been employed for the prevention and treatment of bacterial co-infection and secondary bacterial infections in patients with a viral respiratory infection (e.g., SARS-CoV-2). Although antibiotics do not directly affect SARS-CoV-2, viral respiratory infections often result in bacterial pneumonia. It is possible that some patients die from bacterial co-infection rather than virus itself. To date, a considerable number of bacterial strains have been resistant to various antibiotics such as azithromycin, and the overuse could render those or other antibiotics even less effective. Therefore, bacterial co-infection and secondary bacterial infection are considered critical risk factors for the severity and mortality rates of COVID-19. Also, the antibiotic-resistant as a result of overusing must be considered. In this review, we will summarize the bacterial co-infection and secondary bacterial infection in some featured respiratory viral infections, especially COVID-19.
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http://dx.doi.org/10.1002/iub.2356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7436231PMC
October 2020

The importance of intracellular bacterial biofilm in infectious diseases.

Microb Pathog 2020 Oct 22;147:104393. Epub 2020 Jul 22.

Department of Microbiology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran. Electronic address:

Various bacterial species, previously known as extracellular pathogens, can reside inside different host cells by adapting to intracellular modes by forming microbial aggregates with similar characteristics to bacterial biofilms. Additionally, bacterial invasion of human cells leads to failure in antibiotic therapy, as most conventional anti-bacterial agents cannot reach intracellular biofilm in normal concentrations. Various studies have shown that bacteria such as uropathogenic Escherichia coli, Pseudomonas aeruginosa, Borrelia burgdorferi,Moraxella catarrhalis, non-typeable Haemophilus influenzae, Streptococcus pneumonia, and group A Streptococci produce biofilm-like structures within the host cells. For the first time in this review, we will describe and discuss the new information about intracellular bacterial biofilm formation and its importance in bacterial infectious diseases.
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http://dx.doi.org/10.1016/j.micpath.2020.104393DOI Listing
October 2020

The role of human herpesvirus-6 and inflammatory markers in the pathogenesis of multiple sclerosis.

J Neuroimmunol 2020 Jul 4;346:577313. Epub 2020 Jul 4.

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

Multiple sclerosis (MS) is a destructive autoimmune neuroinflammatory and neurodegenerative disorder of the central nervous system (CNS) with unknown etiology and mechanism of pathogenesis. Pathogens, especially human herpes viruses, have been suggested as environmental factors of the MS and other neuroinflammatory disorders. This study aimed to determine the prevalence of HHV-6 antibody response in MS patients and investigate the levels of pro/anti-inflammatory cytokine and chemokines in MS patients in comparison with healthy subjects. Two hundred sixty-three patients with clinically defined MS (140 females and 123 males), along with 263 healthy subjects (140 females and 123 males), were recruited for this study. After the analysis of HHV-6 seropositivity/seronegativity, the levels of some pro/anti-inflammatory cytokines, including TNF-α, IFN-γ, IL-1β, IL-6, and IL-12 as well as two chemokines, namely CCL-2 and CCL-5 were determined by the enzyme-linked immunosorbent assay (ELISA) method in HHV-6 seropositive/seronegative MS patients and healthy subjects. Our results showed that the serum concentrations of TNF-α, IFN-γ, IL-1β, IL-6, and CCL-5 elevated in HHV-6 seropositive compared with seronegative MS patients (P < .05). Moreover, the levels of IL-12, IL-10, and CCL-2 levels were significantly lower in seropositive MS patients when compared with seronegative MS patients (P < .05). Also, our results revealed that the mean values of the expanded disability status scale (EDSS) were significantly higher in HHV-6 seropositive versus seronegative MS patients (P < .05). In conclusion, we proposed that HHV-6 infection may play a role in MS pathogenesis by changing cytokine signaling in MS patients that may lead to peripheral inflammation.
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http://dx.doi.org/10.1016/j.jneuroim.2020.577313DOI Listing
July 2020

A contemporary review on pathogenesis and immunity of COVID-19 infection.

Mol Biol Rep 2020 Jul 29;47(7):5365-5376. Epub 2020 Jun 29.

Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran.

Emerging of the COVID-19 pandemic has raised interests in the field of biology and pathogenesis of coronaviruses; including interactions between host immune reactions specific, and viral factors. Deep knowledge about the interaction between coronaviruses and the host factors could be useful to provide a better support for the disease sufferers and be advantageous for managing and treatment of the lung infection caused by the virus. At this study, we reviewed the updated information on the pathogenesis of the COVID-19 and the immune responses toward it, with a special focus on structure, genetics, and viral accessory proteins, viral replication, viral receptors, the human immune reactions, cytopathic effects, and host-related factors.
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http://dx.doi.org/10.1007/s11033-020-05621-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7323602PMC
July 2020

Role of microRNAs in Staphylococcus aureus infection: Potential biomarkers and mechanism.

IUBMB Life 2020 09 9;72(9):1856-1869. Epub 2020 Jun 9.

Department of Microbiology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.

Staphylococcus aureus is known as a common pathogen that colonizes 30% of healthy humans. Additionally, this bacterium can cause a number of serious infections, that is, endocarditis, bacteremia, pneumonia, wound, skin infections, and tissue abscesses. A variety of cellular and molecular pathways and targets are involved in response against S. aureus. Among them, microRNAs (miRNAs) have crucial roles in response against S. aureus. In this regard, it has been shown that these molecules exert their regulatory roles via modulating a wide range of events, such as inflammatory reactions, host innate, and adaptive immunity. Current works have provided insight into the crucial involvement of miRNAs in immune defense toward Staphylococcal infections. Herein, we highlighted the current findings on the deregulation of different miRNAs in S. aureus-infected cells. Moreover, we summarized the mechanisms and targets of miRNAs in S. aureus infections.
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http://dx.doi.org/10.1002/iub.2325DOI Listing
September 2020

Serum levels of matrix metalloproteinase-2, -9, and vitamin D in patients with multiple sclerosis with or without herpesvirus-6 seropositivity.

Braz J Infect Dis 2020 Mar - Apr;24(2):144-149. Epub 2020 Mar 31.

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

In recent years, extreme attention has been focused on the role of human herpesvirus-6 (HHV-6) in multiple sclerosis (MS) pathogenesis. However, the pathogenesis of MS associated with HHV-6 infection remains unknown. In this study, we measured the serum levels of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and vitamin D levels in MS patients with HHV-6 infection and MS patients without HHV-6 infection. Five hundred sixty (including 300 females and 260 males) MS patients along with 560 healthy subjects were analyzed for HHV-6 seropositivity using enzyme-linked immunosorbent assay (ELISA). Subsequently, we measured the serum levels of MMP-2, MMP-9, and vitamin D levels in MS patients with HHV-6 infection and MS patients without HHV-6 infection by ELISA. About 90.7% of MS patients (508/560) were seropositive for HHV-6, while 82.3% (461/560) of healthy subjects were seropositive for this virus (p = 0.001). Moreover, there was a significant increase in the levels of MMP-2, MMP-9, and lower vitamin D in the serum samples of MS patients when compared with healthy subjects. Additionally, we demonstrated that the MMP-9 levels in seropositive MS patients were significantly higher than seronegative MS patients (p =  0.001). Finally, our results demonstrated that the mean of expanded disability status scale (EDSS) in seropositive MS patients was significantly higher in comparison to seronegative MS patients (p < 0.05). In conclusion, we suggest that the HHV-6 infection may play a role in MS pathogenesis.
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http://dx.doi.org/10.1016/j.bjid.2020.02.001DOI Listing
June 2020

The biofilm-associated bacterial infections unrelated to indwelling devices.

IUBMB Life 2020 07 9;72(7):1271-1285. Epub 2020 Mar 9.

Department of Microbiology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.

Biofilms are microbial communities established in the self-produced extracellular substances that include up to 80% of associated microbial infections. During biofilm formation, bacterial cells shift from the planktonic forms to aggregated forms surrounded by an extracellular polymeric substance. The bacterial biofilm shows resistance against immune reactions as well as antibiotics and is potentially able to cause disorders by both device-related and nondevice-related infections. The nondevice-related bacterial biofilm infections include dental plaque, urinary tract infections, cystic fibrosis, otitis media, infective endocarditis, tonsillitis, periodontitis, necrotizing fasciitis, osteomyelitis, infectious kidney stones, and chronic inflammatory diseases. In this review, we will summarize and examine the literature about bacterial biofilm infections unrelated to indwelling devices.
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http://dx.doi.org/10.1002/iub.2266DOI Listing
July 2020

Bacterial biofilm in colorectal cancer: What is the real mechanism of action?

Microb Pathog 2020 Feb 8;142:104052. Epub 2020 Feb 8.

Department of Microbiology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran. Electronic address:

Human colorectal cancer is the third most common cancer around the world. Colorectal cancer has various risk factors, but current works have bolded a significant activity for the microbiota of the human colon in the development of this disease. Bacterial biofilm has been mediated to non-malignant pathologies like inflammatory bowel disease but has not been fully documented in the setting of colorectal cancer. The investigation has currently found that bacterial biofilm is mediated to colon cancer in the human and linked to the location of human cancer, with almost all right-sided adenomas of colon cancers possessing bacterial biofilm, whilst left-sided cancer is rarely biofilm positive. The profound comprehension of the changes in colorectal cancer can provide interesting novel concepts for anticancer treatments. In this review, we will summarize and examine the new knowledge about the links between colorectal cancer and bacterial biofilm.
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http://dx.doi.org/10.1016/j.micpath.2020.104052DOI Listing
February 2020

Maraviroc attenuates the pathogenesis of experimental autoimmune encephalitis.

Int Immunopharmacol 2020 Mar 30;80:106138. Epub 2020 Jan 30.

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

It has been shown that the blockade of chemokine receptor type 5 can dampen inflammatory reaction within the central nervous system (CNS). In the present study, we utilized maraviroc, a potent antagonist o CCR5, to examine whether this drug can mitigate neuroinflammation in the spinal cord of mice induced by experimental autoimmune encephalitis (EAE), considered a murine model of multiple sclerosis (MS). For this aim, mice were immunized with myelin oligodendrocyte glycoprotein 35-55 (MOG35-55), followed by pertussis toxin to induce paralysis in EAE mice. The animals intraperitoneally received various doses of maraviroc (5, 25, and 50 mg/kg body weight) when the early clinical signs of EAE appeared. The results demonstrated that the administration of maraviroc led to a marked decrease in the clinical score and improvement in behavioral motor functions. Moreover, our finding indicated that the administration of maraviroc significantly attenuates the infiltration of inflammatory cells to the spinal cord, microgliosis, astrogliosis, pro-inflammatory cytokines, and cell death in EAE mice. The flow cytometry data indicated that a decreased number of CD4+ and CD8+ T cells in the peripheral blood of mice with EAE without affecting the number of T regulatory cells (CD4 + CD25+ forkhead box protein 3+). Finally, it seems that maraviroc is well-tolerated, and targeting CCR5 could open up a new horizon in the treatment of MS.
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http://dx.doi.org/10.1016/j.intimp.2019.106138DOI Listing
March 2020

HIV-1 Tat protein attenuates the clinical course of experimental autoimmune encephalomyelitis (EAE).

Int Immunopharmacol 2020 Jan 9;78:105943. Epub 2019 Dec 9.

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

A growing body of evidence has shown that the human immunodeficiency virus (HIV) infection is associated with a significantly decreased risk of developing multiple sclerosis (MS) in patients with acquired immunodeficiency virus (AIDS). It is thought that two mechanisms are in charge of protection against MS, which include immunosuppression induced by chronic HIV infection (depletion of CD4 + T cells) and antiretroviral medications. HIV-1 encodes several regulatory (Tat and Rev) and accessory (Vpr, Vif, Vpu, and Nef) proteins that have immunosuppressive and immunomodulatory properties. HIV-1 Tat protein is a strongly immunosuppressive agent and can cross the blood-brain barrier (BBB). In this study, we examined the effect of HIV-1 Tat, which is classified into clade B and C, on inflammation, gliosis, apoptosis, and behavioral function in a murine model of MS called experimental autoimmune encephalomyelitis (EAE). For this aim, mice were immunized with myelin oligodendrocyte glycoprotein 35-55 (MOG35-55), followed by pertussis toxin to induce paralysis in EAE mice. After the induction of EAE in mice, the animals intraperitoneally received serial doses of HIV-1 Tat clade B and C (5, 10, and 20 µg/kg body weight) when the early clinical manifestations of EAE were initiated. The results showed that the administration of both clades of the Tat protein led to a marked decrease in the clinical score of EAE mice, as well as improvement in motor-neuron functions. In line with this, Tat considerably reduced the number of apoptotic cells in the sacral region of the spinal cord through the upregulation expression of the Bcl-2 protein. Besides, proinflammatory cytokines such as, IFN-γ, TNF-α, IL-6, and IL-17 were significantly diminished in the serum and spinal cord of EAE mice receiving HIV-1 Tat clade B and C. Conversely, anti-inflammatory cytokines, including IL-10 and IL-4 were elevated in the serum and spinal cord of EAE mice receiving HIV Tat clade B and C when compared with the control group. The immunohistochemical analysis indicated that HIV-1 Tat clade B and C mitigated microgliosis and astrogliosis. The flow cytometry analysis demonstrated that the number of Th1 and Th17cells was significantly decreased in response to TAT administration while the frequency of Th2 cells was markedly increased in the peripheral blood of mice with EAE without influencing the number of T regulatory cells (CD4 + CD25 + forkhead box protein 3 + ). It seems that HIV-1 Tat could be a bona fide therapeutic protein for the alleviation of MS since it has beneficial roles in the suppression of neuroinflammation in MS pathology.
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http://dx.doi.org/10.1016/j.intimp.2019.105943DOI Listing
January 2020

The protective effect of Helicobacter Pylori infection on the susceptibility of multiple sclerosis.

J Neuroimmunol 2019 12 14;337:577069. Epub 2019 Sep 14.

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

In recent years, a possible protective role of Helicobacter pylori (Hp) against autoimmune disease has been reported in an experimental murine model of multiple sclerosis (MS), and there are restricted conflicting epidemiologic data concerning Hp serology in MS patients. This study was aimed to determine the seroprevalence of Hp in MS patients and then investigates pro/anti-inflammatory cytokine levels in MS patients infected with HP and seronegative MS patients. Three hundred eighty-seven patients with MS were included in the study and were adjusted by gender and age to 420 healthy subjects. An enzyme-linked immunoassay (ELISA) was used to determine the presence of specific IgG antibodies against H. pylori in the serum sample of both groups. Some pro/anti-inflammatory cytokines levels were evaluated in seropositive/seronegative MS patients and healthy individuals. Our result showed that in patients with MS HP seropositivity was significantly lower than the healthy individual (P < .0001). Also, we showed that HP seropositive MS patients had lower Expanded Disability Status Scale (EDSS) when compared with seronegative MS patients (P < .011). Moreover, we illustrated that proinflammatory cytokine levels include IFN-γ, TNF-α, IL-6, and IL-17 in MS patients infected with HP were lower than seronegative MS patients. Besides, the levels of anti-inflammatory cytokines include IL-4 and IL-10 was significantly higher in MS patients infected with HP when compared with MS patients seronegative for HP infection. In this study, we indicated that HP infection negatively correlated with MS, and conceivably may act as a protective agent against MS. The precise mechanism behind this protective effect remains elusive. However, it seems HP can modulate cytokine signaling, which involved in MS pathogenesis.
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http://dx.doi.org/10.1016/j.jneuroim.2019.577069DOI Listing
December 2019

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

The frequency of varicella-zoster virus infection in patients with multiple sclerosis receiving fingolimod.

J Neuroimmunol 2019 03 26;328:94-97. Epub 2018 Dec 26.

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

Multiple Sclerosis (MS) is thought to be an autoimmune disease of the central nervous system (CNS), in which the immune system becomes activated, cross the blood-brain barrier (BBB), and cause neuroinflammation and neurodegeneration. Fingolimod is considered a disease-modifying therapy (DMT), possessing immunomodulatory effects on the immune system, especially autoreactive T cells being licensed in lymph nodes. Although the fidelity of the drug is undeniable in the management of disease course, various adverse effects have been reported in some patients taking this medication. In this study, 420 MS patients, consisted of 210 patients receiving interferon-beta (IFN-beta) and 210 patients receiving fingolimod therapies. As a control group, 210 age- and sex-matched healthy individuals were recruited in our study. The levels of anti-VZV IgG and IgM were determined using enzyme-linked immunosorbent assay (ELISA). The presence of VZV DNA in peripheral blood mononuclear cells (PBMCs) was also investigated using the PCR method. The percentage of seropositivity for anti-VZV IgG and anti-VZV IgM in MS patients was 94.8% and 0%, respectively in those taking fingolimod therapy. In patients receiving IFN-beta, the rate of seropositivity for anti-VZV IgG and anti-VZV IgM was 93.8% and 0%, respectively. In healthy individuals, the rate of seropositivity for anti-VZV IgG and anti-VZV IgM was 84.3% and 0%, respectively. The PCR results showed that 7.6% of patients receiving fingolimod were positive for VZV DNA, while none of the healthy subjects nor MS patients taking IFN-beta were positive for DNA of VZV. The statistical analysis indicated that the frequency of VZV DNA in patients receiving fingolimod was significantly (p = .00) higher than MS patients taking IFN-beta and healthy subjects. It seems that the use of fingolimod should be carefully prescribed as the occurrence of VZV infection/reactivation is increased in comparison to other MS patients who receive different therapy.
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http://dx.doi.org/10.1016/j.jneuroim.2018.12.009DOI Listing
March 2019

The Human Immune System against Staphylococcus epidermidis.

Crit Rev Immunol 2019 ;39(3):151-163

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

Staphylococcus epidermidis is one of the major causes of nosocomial infections in humans. This organism can exist as a commensal on the skin. However, it can also lead to severe infections. The immune system has evolved mechanisms to deal with microorganisms and has strategies to combat bacteria. The initial defense against S. epidermidis infections includes the activation of complement complex, recruitment and then killing of the microorganism by effectors. The success of pathogenic S. epidermidis strains has been attributed to their capacity to evade innate immune cells. Extracellular matrix binding protein, polysaccharide intercellular adhesin, and accumulation-associated protein have been found to suppress killing of S. epidermidis by effector cells. PSM constitutes the only kind of exported toxins in S. epidermidis strains and has strong cytolytic features against leukocyte cells. The human innate immune system can be stimulated against S. epidermidis via toll-like receptors that enhance antibacterial reactions, trigger inflammation, and result in the stimulation of immune system effectors, e.g., type-1 interferon (IFN-alpha and IFN-beta), proinflammatory cytokines, and nitric oxide. Proinflammatory cytokines, e.g., interleukin-1, interleukin-6, and tumor necrosis factor are formed from resident human cells and result in migration of the lymphocyte and fever. In this review we will examine the immune system's response against S. epidermidis.
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http://dx.doi.org/10.1615/CritRevImmunol.2019031282DOI Listing
August 2020

The levels of soluble forms of CD21 and CD83 in multiple sclerosis.

J Neuroimmunol 2018 07 13;320:11-14. Epub 2018 Apr 13.

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

Multiple Sclerosis (MS) is a neuroinflammatory disease of the central nervous system (CNS) in which immune system plays a crucial role in progression of the disease. An enormous amount of research has been shown that immune mediators such as cytokines and chemokines are the culprits of MS propagation suggesting that modulation of such molecules may pave the path to hinder the disease development. It has been shown that both CD21 and CD83 contribute to the resolution of inflammation occurred in MS. CD21 and CD83 have also been ascribed to Epstein Barr virus (EBV) infection (the prime suspect of MS causality) and the levels of vitamin D, respectively. Hence, in this study, we measured the serum concentrations of soluble forms of CD21 and CD83 in 255 patients with MS divided into two groups who were receiving interferon-beta (185 MS patients) and fingolimod (70 MS patients) in comparison to 384 healthy individuals. The levels of EBV titers including anti-VCA IgM, anti-VCA IgG and anti-EBNA-1 IgG were also measured. The results showed that the concentration of soluble CD21 (sCD21) was markedly decreased in serum samples of MS patients with respect of controls. Contrarily, the level of soluble CD83 (sCD83) was elevated in MS patients compared to healthy individuals. In addition, the levels of sCD21 and sCD83 were correlated with the titers of EBV. The data showed the significant association between the expanded disability status scale (EDSS) and the levels of both sCD21 and sCD83. It seems that both sCD21 and sCD83 might be good candidate for disease monitoring and can be considered potential biomarkers for the disease activity.
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http://dx.doi.org/10.1016/j.jneuroim.2018.04.005DOI Listing
July 2018
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