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Dear Editor, With the global spread of the COVID-19 pandemic, symptoms such as fever, cough, myalgia, and fatigue, along with laboratory findings of leukocyte count abnormalities and chest radiographic evidence, have been reported as nonspecific symptoms in various variants. Fever was the most common symptom in all variants of the SARS-CoV-2 virus, although evidence suggest that children with the beta variant experienced less fever. Other manifestations, such as diarrhea, vomiting, abdominal pain, and dizziness, have been less common, but may sometimes be the only symptom. In a systematic review on the characteristics of infants with SARS-CoV-2 infection in England, it was reported that the main symptoms at presentation were heatstroke, poor feeding, vomiting, respiratory symptoms, crysis, and lethargy. The clinical symptoms of COVID-19 in children vary depending on the virus variant and correspond to the World Health Organization peak variants of concern. Therefore, clinical guidelines are recommended to perform protected deliveries and reduce the possibility of contracting Covid-19 during delivery and after delivery in infected pregnant women. Standardized testing protocol, avoiding mother-to-child transmission, and providing the best treatment for symptomatic infants are central issues in the management of infections in infants and children with suspected or suspected COVID-19. It is better to use breast milk in the form of expressed milk or powdered milk. PCR-positive neonates should be admitted to a negative pressure isolation room and provided with intubation or airway management services.

Systemic lupus erythematosus (SLE), an autoimmune disease, is among the most prevalent rheumatic autoimmune disorders. It affects autologous connective tissues caused by the breakdown of self-tolerance mechanisms. During the last two decades, stem cell therapy has been increasingly considered as a therapeutic option in various diseases, including parkinson's disease, alzheimer, stroke, spinal cord injury, multiple sclerosis, inflammatory bowel disease, liver disease, diabete, heart disease, bone disease, renal disease, respiratory diseases, and hematological abnormalities such as anemia. This is due to the unique properties of stem cells that divide and differentiate to the specialized cells in the damaged tissues. Moreover, they impose immunomodulatory properties affecting the diseases caused by immunological abnormalities such as rheumatic autoimmune disorders.In the present manuscript, efficacy of stem cell therapy with two main types of stem cells, including mesenchymal stem cell (MSC), and hematopoietic stem cells (HSC) in animal models or human patients of SLE, has been reviewed. Taken together, MSC and HSC therapies improved the disease activity, and severity in kidney, lung, liver, and bone (improvement in the clinical manifestation). In addition, a change in the immunological parameters occurred (improvement in immunological parameters). The level of autoantibodies, including antinuclear antibody (ANA), and anti-double-stranded deoxyribonucleic acid antibodies (dsDNA Abs) reduced. A conversion of Th1/Th2 ratio (in favor of Th2), and Th17/Treg (in favor of Treg) was also detected.In spite of many advantages of MSC and HSC transplantations, including efficacy, safety, and increased survival rate of SLE patients, some complications, including recurrence of the disease, occurrence of infections, and secondary autoimmune diseases (SAD) were observed after transplantation that should be addressed in the next studies.

Today, the world is affected by a COVID-19 epidemic. Early diagnosis can play an important role in the control and prevention of this disease, so the study and practice of biosafety among staff of diagnostic laboratories have a key role in the healthiness of health fighters against COVID-19. In this study, we will review laboratory biosafety considerations for the diagnosis process of SARS-CoV-2 in three phases: (1) the preanalytical phase, (2) the analytical phase, and (3) the postanalytical phase. It should be noted that employees with high-risk underlying health conditions, like lung or heart disease or diabetes, should be moved to lower-risk environments. We believe that this review will help to restrict the risk of developing COVID-19, while working in clinical laboratories.

Abstract Autoimmune diseases, including rheumatoid arthritis that is the most prevalent rheumatic autoimmune disorder, affect autologous connective tissues caused by the breakdown of the self‐tolerance mechanisms of the immune system. During the last two decades, cell‐based therapy, including stem cells and none‐stem cells has been increasingly considered as a therapeutic option in various diseases. This is partly due to the unique properties of stem cells that divide and differentiate from the specialized cells in the damaged tissue. Moreover, stem cells and none‐stem cells, impose immunomodulatory properties affecting the diseases caused by immunological abnormalities such as rheumatic autoimmune disorders. In the present review, the efficacy of cell‐based therapy with four main types of stem cells, including mesenchymal stem cells, hematopoietic stem cells, embryonic stem cells, and human amniotic membrane cells, as well as none‐stem cells, including regulatory T cells, chimeric antigen receptor T cells, and tolerogenic dendritic cells will be evaluated. Moreover, other related issues, including safety, changes in immunological parameters, suitable choice of stem cell and none‐stem cell origin, conditioning regimen, limitations, and complications will be discussed.

Systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and systemic sclerosis (SSc) are the most common rheumatic autoimmune diseases/disorders (RADs) that affect autologous connective tissues as a result of the breakdown of the self-tolerance mechanisms of the immune system. Prolactin, a glycoprotein hormone, has been known for its crucial role in the pathogenesis of these rheumatic autoimmune diseases. In addition to regulating lymphocyte proliferation and antibody synthesis, prolactin is also responsible for regulating cytokine production. Moreover, it contributes to the breakdown of central and peripheral tolerance mechanisms of B lymphocytes. Given the crucial role of prolactin in the pathogenesis of the mentioned RADs, prolactin may contribute to their pathogenesis by the breakdown of tolerance. In the present study, the key role of prolactin to the breakdown of B lymphocyte tolerance and its possible implication for the pathogenesis of these diseases is discussed. Current literature supports prolactin's role in the breakdown of B lymphocyte central and peripheral tolerance mechanisms, such apoptosis, receptor editing, and also anergy. Therefore, prolactin may contribute to the pathogenesis of RADs by the breakdown of B lymphocyte tolerance. However, more investigations, particularly in RA and SSc animal models, are required to precisely address the pathologic role of prolactin.

Background: Interferon-gamma [IFN-γ) is the most important cytokine in the immune system. This protein has been expressed in bacterial cells. However, bacterial cloning is not an easy task. We aimed to clone, express, and purify recombinant mouse IFN-γ and overcome problems in favor of commercial purposes. Materials and Methods: To amplify the gene product for cloning, we primarily designed two specific primers for the target gene. Following PCR amplification, the amplicon was inserted into the pET-21b[+) vector. The E. coli BL21 [DE3) CodonPlus strain was chosen for the expression of the target gene. Finally, the expressed recombinant mouse IFN-γ was assessed through the western blotting method. Results: We performed a cloning process and produced recombinant mouse IFN-γ in an optimal condition. We also noticed that monomeric protein could be transformed to a homodimeric structure which can be observed using the SDS PAGE [SDS-polyacrylamide gel electrophoresis) and western blotting. Conclusion: Experimental conditions strongly affect the large-scale cloning procedures required to be optimized in each laboratory. The expressed recombinant mouse IFN-γ described here is appropriate for commercial purposes.

Since the edifice of conventional medicine is built on the pillars of past achievements, review or re-investigate the old medical manuscripts may lead to significant achievements. Avicenna was a famous Persian medieval physician and one of the pioneers of neuroscience. The aim of this study is to evaluate Avicenna's approach to traumatic brain injury (TBI), based on his main book on medicine, “Canon of Medicine”. Avicenna divided the TBI treatments into three categories: topical therapies, oral therapies, such as diets and medications, and manipulation therapies including phlebotomy, enema, foot bath, cupping, and massage. Although some of these recommendations are supported by current knowledge, many of them are still unknown and need scientific investigation to expand our knowledge of TBI treatments in the medieval period.

Abstract Generally, autoimmune diseases are more prevalent in females than males. Various predisposing factors, including female sex hormones, X chromosome genes, and the microbiome have been implicated in the female bias of autoimmune diseases. During embryogenesis, one of the X chromosomes in the females is transcriptionally inactivated, in a process called X chromosome inactivation (XCI). This equalizes the impact of two X chromosomes in the females. However, some genes escape from XCI, providing a basis for the dual expression dosage of the given gene in the females. In the present review, the contribution of the escape genes to the female bias of autoimmune diseases will be discussed.

Abstract Background Numerous investigations have previously evaluated the association of interleukin (IL) 4 gene polymorphisms and the risk of asthma, conferring inconsistent results. To resolve the incongruent outcomes yielded from different single studies, we conducted the most up-to-date meta-analysis of IL4 gene −589C/T (rs2243250) polymorphism and susceptibility to asthma. Methods A systematic literature search was performed in ISI web of science, Scopus, Medline/PubMed databases prior to September 2020, and the pooled odds ratio (OR) and their corresponding 95% CI were calculated to determine the association strength. Results Literature search led to retrieving of 49 publications (55 case-control studies) containing 9572 cases and 9881 controls. It was revealed that IL4 gene −589C/T polymorphism increased the risk of asthma across all genetic models, including dominant model (OR = 1.22), recessive model (OR = 1.17), allelic model (OR = 1.21), and TT vs. CC model (OR = 1.34), but not the CT vs. TT model. The subgroup analysis by age indicated that IL4 gene -589C/T polymorphism was significantly associated with asthma risk in both pediatrics and adults. Additionally, the subgroup analysis by ethnicity revealed significant association in Asian, American, and Europeans. Finally, subgroup analysis by East Asian and non-East Asian populations indicated significant associations. Conclusions The current meta-analysis revealed that IL4 gene -589C/T polymorphism was a susceptibility risk in both pediatrics and adults in the whole and different ethnic groups.

Background: Fucoidans are a group of sulfated fucose-rich polysaccharides that are isolated from brown marine algae and echinoderms, and recently have been found in seagrasses. Fucoidans, as well as their derivatives, have several beneficial biological effects and therapeutic potentials. In the present study, we aimed to evaluate the anticoagulative effects of two species of brown algae, namely Sargassum angustifolium (S. angustifolium) and Cystoseira indica (C. indica). Methods: Fucoidan C and fucoidan S were extracted by an ethanol/water solvent system from S. angustifolium and C. indicia, respectively. The anticoagulative effects of fucoidan C and fucoidan S were tested on 10 normal serum samples by evaluating the rate of thrombin time (PT) and prothrombin time (PTT). Results: Both fucoidan C and fucoidan S significantly increased PTT. However, no significant difference was observed in PT. Fucoidan C had a greater effect on PTT prolongation compared with fucoidan S. Conclusion: Both fucoidans extracted from S. angustifolium and C. indicia can be used as anticoagulants in biotechnology and human disorders.

Abstract Based on available metabolomic studies, influenza infection affects a variety of cellular metabolic pathways to ensure an optimal environment for its replication and production of viral particles. Following infection, glucose uptake and aerobic glycolysis increase in infected cells continually, which results in higher glucose consumption. The pentose phosphate shunt, as another glucose-consuming pathway, is enhanced by influenza infection to help produce more nucleotides, especially ATP. Regarding lipid species, following infection, levels of triglycerides, phospholipids, and several lipid derivatives undergo perturbations, some of which are associated with inflammatory responses. Also, mitochondrial fatty acid β-oxidation decreases significantly simultaneously with an increase in biosynthesis of fatty acids and membrane lipids. Moreover, essential amino acids are demonstrated to decline in infected tissues due to the production of large amounts of viral and cellular proteins. Immune responses against influenza infection, on the other hand, could significantly affect metabolic pathways. Mainly, interferon (IFN) production following viral infection affects cell function via alteration in amino acid synthesis, membrane composition, and lipid metabolism. Understanding metabolic alterations required for influenza virus replication has revealed novel therapeutic methods based on targeted inhibition of these cellular metabolic pathways.

Background: The production of recombinant proteins in Escherichia coli is one of the most valuable achievements in biotechnology, with many therapeutic and diagnostic applications; however, the aggregation and misfolding of proteins that result in the formation of insoluble inclusion bodies is a disruptive factor in this process. Various solubilization and refolding methods can be used to improve recombinant protein conformation. In this study, we applied a dilution method with a refolding buffer to produce a native form of soluble immature mouse TGF-β1. Materials and Methods: The TGF-β1 cDNA which encodes the protein without the signal peptide, was cloned into the pET21-b (+) vector. The target protein was expressed by the transformation of E. coli BL21 cells with the plasmid. The resulting inclusion bodies were solubilized and then diluted in the refolding buffer to make a protein with native structure. Results: Following PCR of the recombinant plasmid with T7 primers, electrophoresis and sequencing of the amplified product indicated 100% identity of the target sequence with the murine TGF-β1 gene. Finally, the protein solubility and immuno-reactivity were confirmed a 44 kDa protein which conducted with the anti-TGF-β1-specific polyclonal antibody on a western blot. Conclusion: Our dilution method and refolding buffer effectively converted aggregated immature mouse TGF-β1 to a soluble and immuno-reactive form.

Fibroblast-like synoviocytes (FLSs) produce lots of inflammatory molecules that trigger immune responses and intensification the inflammation and thereby play important roles in Rheumatoid Arthritis )RA( pathogenesis. Due to the important roles of toll-like receptor 4 (TLR4) in cytokine production and inflammation, we aimed to evaluate the effects of TAK-242 (Resatorvid) on interleukin (IL)1-β, IL-6, TNF-α, and TLR4 expression and two important proteins of nuclear factor-κB (NF-κB) signaling pathway (Ikβα and pIkβα) in RA and trauma FLSs. FLSs were isolated from synovial tissues of trauma (n=10) and RA (n=10) patients and cultured in Dulbecco's Modified Eagle Medium (DMEM). 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) was performed to evaluate the cytotoxicity effects of TAK-242 on the RA FLSs. Real-time PCR was performed to measure the expression level of IL1-β, IL-6, TNF-α, and TLR4 genes in Lipopolysaccharide (LPS) and TAK-242 treated FLSs. Furthermore, the treated FLSs were evaluated for protein levels of Ikβα and pIkβα by western blot. The baseline expression of IL1-β, IL-6, TNF-α, and TLR4 showed no significant differences between healthy and RA FLSs. LPS stimulated FLSs significantly increased mRNA levels of IL-1β, IL-6, TNF-α, and TLR4 genes in both the healthy and RA FLSs compared with that of their control groups, and pretreatment with TAK-242 reversed the effect. Furthermore, LPS-stimulated FLSs significantly increased the level of pIkβα in both the healthy and RA FLSs compared with that of their control groups, and pretreatment with TAK-242 reversed the effect. We provide the data that TAK-242 through inhibiting the NF-κB signaling pathway may modulate TLR4-mediated inflammatory responses and could be considered as a potential therapeutic agent for RA patients.

Backgrounds Many proteins have been expressed so far in bacterial host. Due to its simple culture conditions, having a short life cycle, and easily genetic manipulation, E.coli have been regarded as a preferable host to produce recombinant proteins, but protein cloning in bacterial host have many challenges. Therefore, we aimed to review some of these problems by an experience from mice IL-2 recombinant. Materials and methods: cDNA synthesis was performed after RNA extraction of mouse splenocytes. PCR product purification carried out after IL-2 coding sequence amplification and was ligated into the pET-21b (+) vector and transformed into the competent BL21 E.coli. Expression and purification of recombinant mouse IL-2 were done using IPTG inducer and metal affinity chromatography respectively. Results: DNA sequencing confirmed the accuracy of the insertion process. A 23 kDa exogenous protein was observed on the SDS-PAGE. Specificity and concentration of produced mouse recombinant IL-2 protein were confirmed by western blotting and BCA methods. Conclusion: Recombinant IL-2 was produced in BL21 and pET-21b (+) expression system at 24°C in the soluble form.

Fibroblast-like synoviocytes (FLSs) have been introduced in recent years as a key player in the pathogenesis of rheumatoid arthritis (RA), but the exact mechanisms of their transformation and intracellular pathways have not yet been determined. This study aimed to investigate the role of fibroblast activation protein-alpha (FAP-α) in the regulation of genes involved in the transformation and pathogenic activity of RA FLSs. Synovial FLSs were isolated from RA patients and non-arthritic individuals (n=10 in both groups) and characterized; using immunocytochemistry and flow cytometry analysis. FLSs were divided into un-treated and Talabostat-treated groups to evaluate the FAP-α effect on the selected genes involved in cell cycle regulation (p21, p53, CCND1), apoptosis (Bcl-2, PUMA), and inflammatory and destructive behavior of FLSs (IL-6, TGF-β1, MMP-2, MMP-9, P2RX7). Gene expression analysis was performed by quantitative real-time polymerase chain reaction (qRT-PCR), and immunoblotting was carried out to evaluate FAP-α protein levels. The basal level of FAP-α protein in RA patients was significantly higher than non-arthritic control individuals. However, no differences were observed between RA and non-arthritic FLSs, at the baseline mRNA levels of all the genes. Talabostat treatment significantly reduced FAP-α protein levels in both RA and non-arthritic FLSs, however, had no effect on mRNA expressions except an upregulated TGF-β1 expression in non-arthritic FLSs. A significantly higher protein level of FAP-α in FLSs of RA patients compared with that of healthy individuals may point to the pathogenic role of this protein in RA FLSs. However, more investigations are necessary to address the mechanisms mediating the FAP-α pathogenic role in RA FLSs.

In the last two decades, we have witnessed three major epidemics of the coronavirus human disease namely, severe acute respiratory syndrome (SARS), Middle Eastern respiratory syndrome, and more recently an ongoing global pandemic of coronavirus disease 2019 (COVID-19). Iran, a country of nearly 84 million, in the Middle East, severely involved with the COVID-19 disease. A documented multidimensional approach to COVID-19 disease is therefore mandatory to provide a well-balanced platform for the concerned medical community in our county and beyond. In this review, we highlight the disease status in Iran and attempt to provide a multilateral view of the fundamental and clinical aspects of the disease including the clinical features of the confirmed cases, virology, pathogenesis, epidemiology, and laboratory methods needed for diagnosis.

Several studies have demonstrated that the genetic polymorphisms in the genes encoding immune regulatory molecules, namely cytotoxic T-lymphocyte-associated protein 4 (CTLA4) and CD28, play a fundamental role in susceptibility to rheumatoid arthritis (RA). Several disperse population studies have resulted in conflicting outcomes regarding the genetic polymorphisms in these genes and RA risk. This systematic review and meta-analysis study was performed to reach a conclusive understanding of the role of single-nucleotide polymorphisms (SNPs) of CTLA4-rs231775, CTLA4-rs5742909, and CD28-rs1980422 in susceptibility to RA. Databases (ISI Web of Science, MEDLINE/PubMed, and Scopus) were searched to find the case–control studies surveying the association of CTLA4 gene rs231775, CTLA4 gene rs5742909, and CD28 gene rs1980422 polymorphisms and RA susceptibility in different population until August 2020. Association comparison between the polymorphisms and RA proneness was assessed using pooled odds ratio (OR) and their corresponding 95% confidence interval. This study was conducted on 16 population studies, comprising 1078 RA patients and 1118 healthy controls for CTLA4-rs231775, 2193 RA patients and 2580 healthy controls for CTLA4-rs5742909, and 807 RA patients and 732 healthy controls for CD28-rs1980422. Analysis indicated that G-allele, GG and GA genotypes, and dominant model for rs231775, recessive model for rs5742909, and C-allele, CC and CT genotypes, and recessive model for rs1980422 were significantly associated with increased RA risk. This meta-analysis showed that genetic polymorphisms of both immune inhibitory and activating genes, including CTLA4-rs231775, CTLA4-rs5742909, and CD28-rs1980422 polymorphisms, may increase susceptibility to RA.

Survivin, an antiapoptotic molecule from inhibitor of apoptosis protein (IAP) family, is most known for its implication in cancer as there are some efforts to apply it for diagnostic as well as therapeutic purposes in oncology. On the other hand, it could be a useful molecule to be positively targeted when trying to save tissue and promote cells viability. Since protecting the allograft from ischemia reperfusion injury and inflammation-induced damage is a considerable objective in transplantation, it is reasonable to take advantage from antiapoptotic agents like survivin in order to achieve this goal. However, survivin’s potential ability to induce malignancies makes some concerns about its use in clinic. The other barrier is this molecule’s involvement in lymphocytes development and proliferation which might increase the risk of graft rejection due to adaptive immune system overactivation. In this review we summarize the few studies carried out about survivin’s effect on graft survival and probable advantages and disadvantages of its overexpression in transplantation.

Abstract This paper examines a new topology of the AC‐AC Z‐source converter based on asymmetric Gama structure is proposed. The proposed converter has all the common features such as common ground between input and output, realizing the continuous input current and the ability of boost in‐phase and buck out of‐phase. In order to generate a high voltage gain in the proposed converter, a coupled inductor with Gama structure is used. In this structure, as the turn ratio approaches to one, it gives a higher voltage gain. In order to damping the voltage and current overshoots on the proposed converter switches, a safe commutation strategy is used. Due to the specific topology of the proposed converter, the output filter has been eliminated, so the size and cost of the proposed converter are reduced. Circuit analysis and performance principles are presented in detail and a laboratory prototype implemented to confirm the practicality of the proposed converter.