sayed-hamidreza mozhgani

Adult T-cell leukemia/lymphoma (ATLL) is a cancer with a very poor prognosis. ATLL has four subgroups, acute, chronic, lymphoma, and smoldering, with very different prognoses. In this study, we tried to better understand the pathogenesis of ATLL and the differences between its subgroups by using gene expression data and bioinformatics methods.

Genes with altered expression were identified among different types of ATLL. In order to determine the key genes, the network of protein interactions between the resulting genes was constructed. After screening the hub genes based on the network centrality indices, the cell signaling pathways related to them were identified.

Comparing the acute type with the chronic and silent types, the cell signaling pathways involved in regulating the function of the immune system are expressed differently. In comparison of acute and chronic type with healthy people, genes related to malignancy are involved. In comparing the silenced type with healthy individuals, the pathways related to infections are disrupted. In the secondary comparison, it was found that the genes related to cell proliferation and malignancy in the acute form were expressed more and the genes related to the immune system were less expressed in these patients than in the rest of the population.

It seems that manipulations by the virus resulting in immune escape and also in increased proliferation of infected cells have a decisive role in the occurrence of the aggressive type of the disease. Further investigations can lead to the development of new diagnostic methods, determining prognosis and even the detection of targets for gene therapy.

HTLV-1 is responsible for two important diseases, HAM/TSP and ATLL. Approximately 10 to 20 million people are infected with HTLV-1 worldwide. Identifying altered genes in different cancers is crucial for finding potential treatment strategies. One of the proteins of the RAS/MAPK signaling pathway is MEK1, which is made from the MAP2K1 gene. The effects of the MAP2K1 gene on the MAPK signaling pathway are not yet fully elucidated. The current study aims to determine the MAP2K1 gene mutations and the level of MAP2K1 gene expression in ATLL patients compared to healthy individuals.

Ten ATLL and 10 healthy control individuals were investigated in this study. We used ELISA test to screen anti-HTLV-I antibodies and PCR for confirmation of infection. Then, we extracted total RNA from fresh whole blood, and cDNA was synthesized. The expression levels of the MAP2K1 gene were examined by qRT-PCR, and to check possible mutations in the MAP2K1 gene; all samples were sequenced and analyzed by BioEdite Software.

MAP2K1 gene expression in the ATLL group was significantly higher than in the healthy control (P=0.001). The mutational sequencing analysis showed nucleotide 212 (S→R) change and identification mutations at different nucleotides that were entirely different from the nucleotide mutations defined in the UniProt database.

These results could be a perspective in the prevention, prognosis, and targeted treatment of diseases in which the MAP2K1 gene plays a vital role.

Human parechoviruses (HPeV) are rapidly evolving picornaviruses that may cause sepsis-/meningitis-like illness in infants. The present study aimed to evaluate the occurrence and quantity of human parechovirus in 160 cerebrospinal fluid samples of children under 5 years old with meningitis and meningoencephalitis hospitalized at Karaj Imam Ali Hospital.

160 CSF samples were collected during September 2019 to October 2020 in karaj province, Iran from hospitalized children with meningitis and meningoencephalitis. They were subject to detect HPeV using consensus primers targeted to their 5′UTR s.

Out of 160 samples of cerebrospinal fluid, two samples (1.25%) were positive for human parechovirus. The maximum viral load of HPeV was 5.6 × 106 copies / ml in December and in a 3.5 years old female patient and the minimum viral load was 3.2 × 104 copies / ml in February in a 4.5 years old female patient.

In this study for the first time, the presence of human parecovirus in the cerebrospinal fluid samples of children under 5 years of age with meningitis and meningoencephalitis hospitalized in Imam Ali Karaj Hospital reported. Two samples out of 160 cerebrospinal fluid samples were positive. It indicates the relationship between human parechovirus and neurological disorders

The coronavirus disease 2019 (COVID-19) pandemic has prompted researchers to look for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogenicity in depth. Immune system dysregulation was one of the major mechanisms in its pathogenesis. The evidence regarding the levels of interferons (IFNs) and pro- and anti-inflammatory cytokines in COVID-19 patients is not well-established.

This study evaluated the expression level of type-I, II, III IFNs, along with interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-10 (IL-10), and FOXP3 genes in patients with severe COVID-19 to provide additional insights regarding the regulation of these cytokines during COVID-19 infection.

Peripheral blood mononuclear cells were isolated from two groups, including severe COVID-19 patients and healthy controls. Ribonucleic acid was extracted to evaluate the expression level of IFN-a, IFN-b, IFN-g, IFN-la, IL-1, IL-6, IL-10, and FOXP3 genes using real-time polymerase chain reaction. The correlations between the expression levels of these genes were also assessed.

A total of 40 samples were divided into two groups, with each group consisting of 20 samples. When comparing the severe COVID-19 group to the controls, the expression levels of IFN-g, tumor necrosis factor-alpha (TNF-), IL-6, and IL-10 genes were significantly higher in the severe COVID-19 group. The two groups had no significant differences in IFN-a, IFN-b, IFN-la, IL-1, and FOXP3 expression. The correlation analysis revealed a negative correlation between type I and type III IFNs (i.e., IFN-a and IFN-la) and proinflammatory cytokines (i.e., IL-1 and IL-10).

This study suggests the possible upregulation of IFN-g, IL-6, IL-10, and TNF-during SARS-CoV-2 pathogenicity. The preliminary findings of this study and those reported previously show that the levels of IFNs and pro- and anti-inflammatory cytokines are not uniformly expressed among all COVID-19 patients and might differ as the disease progresses to the severe stage.

 Human T-cell lymphotropic virus type 1 (HTLV-1) is the etiological agent of adult T-cell leukemia/lymphoma (ATLL) without any specific antiviral.

 This study aimed to evaluate the expression level of inflammatory chemokines and pro-inflammatory cytokines in ATLL patients, asymptomatic carriers (ACs), and healthy individuals to assess the role of these inflammatory markers in ATLL pathogenicity.

 This study was conducted from May 2021 to August 2022. The ATLL blood samples were collected from the oncology wards of Imam Khomeini, Shariati, and Imam Hossein hospitals, in Tehran, Iran. The blood samples of ACs and normal control subjects were collected from blood donors referred to blood transfusion centers of Tehran and Alborz provinces, Iran. RNA extraction, complementary DNA (cDNA) synthesis, and real-time polymerase chain reaction (PCR) were done in targeted sample groups to investigate the correlation and expression rate of C-C motif chemokine ligand 3 (CCL3), C-C motif chemokine ligand 4 (CCL4), C-X-C motif chemokine ligand 8 (CXCL8), interleukin 23 subunit alpha (IL-23A), and interleukin 17 A (IL-17A).

 A total of 30 samples were collected from 3 groups. The CCL3, CCL4, CXCL8, and IL-17A messenger RNA (mRNA) expression levels were significantly upregulated in the ATLL groups. There was a significant difference between CCL3 expression between the ACs and ATLL groups. In addition, CCL4 and CXCL8 expression levels were more significant in the ATLL group than in the normal control group. The IL-17A expression level significantly increased between groups. The IL-23A expression levels had no significant differences between the ATLL, ACs, and normal control groups.

 This study showed significant upregulation of pro-inflammatory cytokines and chemokines mRNAs in HTLV-1–associated ATLL compared to the ACs and normal control groups. Conducting more experiments to investigate the therapeutic effect of chemokines/cytokines in ATLL is essential.

There are reports of ocular tropism due to respiratory viruses such as severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Various studies have shown ocular manifestation in coronavirus disease-2019 (COVID-19) patients. We aimed to identify ophthalmic manifestations in COVID-19 patients and establish an association between ocular symptoms and SARS-CoV-2 infection.

A systematic search of Medline, Scopus, Web of Science, Embase, and Cochrane Library was conducted for publications from December 2019 to April 2021. The search included MeSH terms such as SARS-CoV-2 and ocular manifestations. The pooled prevalence estimate (PPE) with 95% confidence interval (CI) was calculated using binomial distribution and random effects. The meta-regression method was used to examine factors affecting heterogeneity between studies.

Of the 412 retrieved articles, 23 studies with a total of 3,650 COVID-19 patients were analyzed. The PPE for any ocular manifestations was 23.77% (95% CI: 15.73-31.81). The most prevalent symptom was dry eyes with a PPE of 13.66% (95% CI: 5.01-25.51). The PPE with 95% CI for conjunctival hyperemia, conjunctival congestion/conjunctivitis, and ocular pain was 13.41% (4.65-25.51), 9.14% (6.13-12.15), and 10.34% (4.90-15.78), respectively. Only two studies reported ocular discomfort and diplopia. The results of meta-regression analysis showed that age and sample size had no significant effect on the prevalence of any ocular manifestations. There was no significant publication bias in our meta-analysis.

There is a high prevalence of ocular manifestations in COVID-19 patients. The most common symptoms are dry eyes, conjunctival hyperemia, conjunctival congestion/conjunctivitis, ocular pain, irritation/itching/burning sensation, and foreign body sensation.

HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a neuroinflammatory disorder associated with HTLV-1. Cytokines and inflammatory mediators have a major role in forming inflammation in HAM/TSP patients. This study aimed to measure the levels of IL-32, a proinflammatory cytokine associated with autoinflammatory disorders, and also cyclooxygenase -2 (COX-2) as a key mediator of inflammatory pathways in HAM/TSP patients and HTLV-1 asymptomatic carriers (ACs). Peripheral blood monocyte cells (PBMCs) were isolated from HAM/TSP patients, ACs, and healthy controls (HCs), and DNA and RNA were extracted to evaluate HTLV-1 proviral load (PVL) and expression of IL-32 and COX-2, using real-time PCR. Serum levels of IL-32 were determined by using an ELISA assay. The expression level of IL-32 was significantly higher in ACs compared with HAM/TSP patients and HCs (p 0.05, respectively). There were no statistically significant differences in the expression levels of Cox-2 and protein levels of IL-32 between the study groups.  HTLV-1 PVL was higher in HAM/TSP patients compared with ACs.  Results showed increased mRNA levels of IL-32 in ACs. Since HTLV-1 PVL in ACs is lower than in HAM/TSP patients, it could be concluded that IL-32 might be an HTLV-1 inhibitor that seems to control virus replication. Despite the difference in IL-32 mRNA levels between study groups, no statistically significant differences were observed in IL-32 serum levels. Also, there were no significant differences in COX-2 expression.

SARS-CoV-2 emerging from Wuhan, China is a member of the Coronaviridae family, which has so far infected and killed many people. The SARS-CoV-2 pandemic affected various aspects of life in Iran and Worldwide, and governments have imposed quarantines and travel bans on an unprecedented scale. The virus causes COVID-19, which can spread through close contact with the infected person, contaminated equipment, and suspended air droplets. The most common symptoms of the disease include fever, cough, shortness of breath, gastrointestinal symptoms, and diarrhea. In severe cases, the lung infection can occur, which causes Severe Acute Respiratory Syndrome that leads to ICU admission and even death.   Besides, this infection can cause gastrointestinal, neurological, and renal impairments. Not merely, this new coronavirus has infected many more people worldwide in comparison to MERS and SARS, but also it has killed more people. Patients with underlying diseases such as hypertension, diabetes, respiratory problems, kidney disease, heart disease and Immunodeficiency are at higher risk of infection and potential death. Also, the risk of death and complication increases in older adults, while most of the infected children are asymptomatic. Some infected people may have mild or no symptoms but can still transmit the disease and spread it to others. To diagnose COVID-19, serology tests, and level of ESR, CRP and other acute-phase reactants are helpful, whereas molecular tests, such as RT-PCR tests, that detect the virus’s genetic material are still the golden standard. Also, CT scan detects lung involvement; Ground-glass opacification, especially in lower lobes and subpleural region, is the most common CT characteristic, although it is not specific for COVID-19. Because the disease is difficult to diagnose, hard to prevent and challenging to treat, it has become a major concern for many countries. This review aims to gather existing information in the fields of virology, molecular pathogenesis, disease symptoms, epidemiology, clinical presentations, diagnosis, treatment, and the spread of the disease. This study also provides evidence-based prevention and treatment strategies for health policymakers, doctors, nurses, and practitioners in the field of public health, including researchers and students.

The ‘a’ determinant domain of hepatitis B surface antigen (HBsAg) (positions 124 to 147) is recognized by antibodies raised either naturally or induced by vaccine. Failure to protect against hepatitis B virus (HBV) infection may occur due to the conformational changes of ‘a’ determinant induced by mutations.
The present study analyzed the molecular and three-dimensional (3D) characteristics of the HBsAg ‘a’ determinant mutations among Iranian chronic hepatitis B (CHB) patients, who were vaccine and drug naive.
Eighty patients with HBsAg positive test results were selected according to the data extracted from questionnaires. Serologic and molecular assays were performed using real-time Polymerase Chain Reaction (PCR) and subsequently surface nested PCR on CHB patients. Next, an extensive mutational analysis was applied following direct sequencing on HBsAg amplified genes. The potential impacts of altered antigenic and 3D properties of amino acid substitutions were carried out using bioinformatics approaches.
All patients were negative for HBeAg and positive for anti-HBe. Mutational analysis showed that 60 (75%) of 80 patients had at least one amino acid substitution. Several mutations were found in ‘a’ determinant (P127L, P127T, G130N, and S136Y). Bioinformatics investigations indicated that all mutations induced a conformational change in ‘a’ determinant region. P127L substitution led to a considerable decreased HBsAg antigenicity compared to other mutants.
The current analyses revealed that the studied mutations induced a local change in the ‘a’ determinant conformation. These findings could be useful for the design of HBsAg detection assays, which may significantly improve the ability to detect particular HBsAg mutants.

The role of different viral proteins in the progression of the disease to cirrhosis is not completely understood. The ARFP/F protein is a newly described protein synthesized from the +1 or -2 reading frames of the core protein gene, which its function remains unknown. The purpose of this study is to detect specific antibodies to HCV-ARF/Core+1 protein in cirrhotic and non-cirrhotic patients with HCV and investigate any possible association. ARF/Core+1 recombinant proteins from HCV genotype 1a were expressed in Escherichia coli, and purified. Using an enzyme-linked immunosorbent assay, we assessed the prevalence of anti-ARF/Core+1 antibodies in 50 cirrhotic and 50 non-cirrhotic hepatitis C patients. All 50 cirrhotic patients were positive for anti-ARF/Core+1 antibody, while only 80% positive samples among non-cirrhotic patients were detected. The titer of anti-ARF/Core+1 antibody was also significantly higher in patients with cirrhosis than in non-cirrhotic patients. Compared to 80% positive samples among non-cirrhotic patients all 50 cirrhotic patients were positive for anti-ARF/Core+1 antibody and titer of anti-ARF/Core+1 antibody was significantly higher in patients with cirrhosis than in non-cirrhotic. These results suggest that ARF/Core+1 protein is associated with cirrhosis. A possible causative association between ARF/Core+1 and cirrhosis as well as the mechanism of this association needs to be further investigated.

Rabies is a widespread neurological zoonotic disease causing significant mortality rates, especially in developing countries. Although a vaccine for rabies is available, its production and scheduling are costly in such countries. Advances in recombinant DNA technology have made it a good candidate for an affordable vaccine. Among the proteins of rabies virus, the Glycoprotein (RVG) has been the major target for new vaccine development which plays the principalrole in providing complete protection against RV challenge. The aim of this study is to produce recombinant RVG which could be a DNA vaccine candidate and to evaluate the efficiency of this construct in a prime-boost vaccination regimen, compared to commercial vaccine. Cloning to pcDNA3.1(+) and expression of rabies virus glycoprotein gene in BSR cell line were performed followed by SDS-PAGE and Western blot analysis of the expressed glycoprotein. The resulting genetic construct was used as a DNA vaccine by injecting 80 µg of the plasmid to MNRI mice twice. Prime-Boost vaccination strategy was performed using 80 µg plasmid construct as prime dose and the second dose of an inactivated rabies virus vaccine. Production of rabies virus neutralizing antibody (RVNA) titers of the serum samples were determined by RFFIT. In comparisons between heterologous prime-boost vaccination strategy and DNA vaccinations, the potency of group D that received Prime-Boost vaccine with the second dose of pcDNA3.1(+)-Gp was enhanced significantly compared to the group C which had received pcDNA3.1(+)-Gp as first injection. In this study, RVGP expressing construct was used in a comparative approach between Prime-Boost vaccination strategy and DNA vaccination and compared with the standard method of rabies vaccination. It was concluded that this strategy could lead to induction of acceptable humoral immunity.

Rabies is an acute encephalitis that causes more than 60,000 deaths worldwide. The only way to save individuals bitten by a rabies-infected animal is the timely use of effective vaccines. Treatment with new generation vaccines is expensive. Therefore, there is a global movement towards the production of less expensive vaccines which retain and improve upon the quality and effectiveness of the vaccine. Production and evaluation of non-classical vaccines is one of the approaches taken in this regard. In this study, we describe a new eukaryotic expression system to express the nucleoprotein N gene of rabies virus which, if suitable, may be evaluated for anti-rabies vaccine production. The complete sequence of the N gene of rabies virus PV subtype was amplified by real-time polymerase chain reaction and cloned into the pCDNA3.1(+) vector. The cloned gene was excised from the vector by restriction enzyme digestion and sequenced. Due to mutations detected in the N gene, the gene coding sequence was purchased as a recombinant pGH/N vector. Vector pGH/N was amplified and following enzymatic digestion, the excised N gene was once again cloned into vector pCDNA3.1(+). Successful cloning was confirmed using restriction digests and quick check. The recombinant vector pCDNA3.1(+)/N was transformed into cultured BSR cells and protein N expression was analyzed using fluorescent antibody test (FAT). Electrophoresis confirmed amplification of the nucleoprotein N gene and subsequent restriction enzyme digestion showed that the N gene had been successfully cloned into the recombinant pCDNA3.1(+)/N vector. However, DNA sequencing revealed the presence of mutations within the N gene. Restriction digest of the commercial pGH/N vector showed that the N gene had been excised from the vector. Successful cloning of the N gene into the pCDNA3.1(+) expression vector was confirmed using restriction digests and quick check. Protein expression in BSR cells was assayed by immunostaining with anti-ribonucleocapsid FITC-conjugated antibody and visually confirmed by fluorescence microscopy. This study showed that the protein N of rabies virus subtype PV can be expressed in a eukaryotic expression system using the pCDNA3.1(+) expression vector.