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Silymarin is a polyphenolic flavonoid extracted from milk thistle. It has potent immunomodulatory effects and can inhibit the replication of influenza A virus (IAV). The present study aimed to determine the inflammatory and anti-inflammatory cytokine secretion patterns in mice before and after silibinin treatment. For this, bronchoalveolar lavage (BAL) fluids were collected from the thoracic cavity 5 days after the intervention, and viral quantification was performed using TaqMan Real-time PCR. Enzyme-linked immunosorbent assay (ELISA) was used to evaluate IFN‐γ and IL-10 levels in serum and BAL samples. Finally, pathological damage to lung tissue was assessed by pathologists. The results reveal that silibinin pretreatment exhibits a dose-dependent immunomodulatory effect on IFN-γ and IL-10 levels. After the virus challenge, silibinin reduced immune cell infiltration in mouse BAL fluid. These data similarly suggest a remarkable immunomodulatory effect of silibinin. Silibinin also decreased lung damage following the virus challenge in the post-treatment group, but its lung protective properties seem to be due to a different mechanism than when it was administered before infection. Finally, high doses of silibinin (post-treatment) significantly reduced viral load in BAL fluid compared to the virus challenge group. These results support the idea that therapies aimed at moderating immune and inflammatory responses are essential to decrease the mortality rate caused by IAV infection. Silibinin has strong immunomodulatory properties, can inhibit IAV infection, and reduces lung tissue damage in a dose-dependent manner.

Aim Since COVID-19 has set the state of health of the country in an emergency, it is natural that in such circumstances, violation of some principles of professional ethics is inevitable. This study aimed to identify and prioritize ethical challenges in the clinical services of patients with confirmed coronavirus disease in Iran's hospitals. Design This study was a mixed method with an exploratory sequential design. Methods This study was done in 2 qualitative and quantitative phases. In the qualitative phase, a systematized review was conducted and in the quantitative phase, a questionnaire of 35 questions based on the results of Phase 1 was formulated and completed. Results The challenges related to the provider of clinical services (physicians and nurses), the recipients of clinical services (patients), and the organizational challenges had the most significant importance, respectively ( P

Abstract COVID-19 is a highly contagious virus that uses Angiotensin-converting enzyme 2 (ACE2) as a receptor to enter human cells. The virus leads to an increase in inflammatory cytokines (i.e. IL-6) and an impaired coagulation system, which can cause serious complications during and after the disease. Physical exercise has been shown to improve COVID-19 complications through various mechanisms, such as modulation of the immune and coagulation systems. Therefore, this study investigated the effects of 8 weeks of training on inflammatory, coagulation, and physical factors in patients with COVID-19 during the recovery phase. Twenty-seven male and female volunteers (age 20–45 years) who recently recovered from COVID-19 were assigned to the control (n = 13) or the training group (n = 14). Blood samples, aerobic capacity and muscle endurance were collected 24 h before the start of the interventions and 24 h after the final training session in week 4 and 48 h after the final training session in week 8. IL-6, ACE2, fibrinogen, and D-dimer were measured using ELISA. The training group showed a significant increase in muscle endurance (p = 0.004) and aerobic capacity (p = 0.009) compared to the control group. Serum levels of IL-6 and fibrinogen decreased in the training group but this decrease was not statistically significant (p > 0.05). Despite a slight increase in the quality of life and sleep in the training group, no statistically significant difference was observed between the training and the control group. It appears that physical training has beneficial effects on the coagulation system, inflammatory factors, and sleep quality and can facilitate the recovery of COVID-19 patients.

Abstract Background The antiviral properties of metal nanoparticles against various viruses, including those resistant to drugs, are currently a subject of intensive research. Recently, the green synthesis of nanoparticles and their anti-viral function have attracted a lot of attention. Previous studies have shown promising results in the use of Arabic gum for the green synthesis of nanoparticles with strong antiviral properties. In this study we aimed to investigate the antiviral effects of MnO2 nanoparticles (MnO2-NPs) synthesized using Arabic gum, particularly against the influenza virus. Methods Arabic gum was used as a natural polymer to extract and synthesize MnO2-NPs using a green chemistry approach. The synthesized MnO2-NPs were characterized using SEM and TEM. To evaluate virus titration, cytotoxicity, and antiviral activity, TCID50, MTT, and Hemagglutination assay (HA) were performed, respectively. Molecular docking studies were also performed to investigate the potential antiviral activity of the synthesized MnO2-NPs against the influenza virus. The molecular docking was carried out using AutoDock Vina software followed by an analysis with VMD software to investigate the interaction between Arabic gum and the hemagglutinin protein. Results Simultaneous combination treatment with the green-synthesized MnO2-NPs resulted in a 3.5 log HA decrement and 69.7% cellular protection, which demonstrated the most significant difference in cellular protection compared to the virus control group (p-value

Natural ventilation is one of the most important factors in creating thermal comfort. Wind catchers, which are considered as important and historical elements of Iranian architecture, have been recognized as a passive cooling system. These cooling systems provide air conditioning for buildings through renewable energy sources such as wind, and are used to ensure comfort for individuals in hot and dry areas. Today, considering the increase in environmental pollution and the importance of non-renewable energy sources, the role of natural ventilation in building construction is important in terms of environmental compatibility. Additionally, due to the significance of wind catchers in creating natural ventilation, this research has focused on examining this functional element in architecture. The wind catchers in Kerman city are an example of energy saving by buildings in hot and dry climates. Therefore, by studying and understanding the precise, quantitative, and numerical aspects of how wind catchers function and behave, they can be considered as an effective step in achieving climate-adaptive design solutions. The present study assumes that in spaces where natural ventilation is provided by wind catchers, there can be a significant relationship between proportions and form of space on wind speed and performance, and compares the performance of wind catchers in selected samples with different forms, dimensions, and proportions to identify the optimal form for natural ventilation in contemporary architecture. The research method used in this study is descriptive-analytical, which first used library resources and photography, then observations of the studied buildings, and finally, CFD analysis using Design Builder software. The results of the analysis indicate differences in wind speed and performance in the studied samples with different forms and proportions, and after performing calculations, the optimal form in terms of performance and wind behavior has been determined.

Angiogenesis is a hallmark of cancer biology, and neoadjuvant therapies targeting either tumor vasculature or VEGF signaling have been developed to treat solid malignant tumors. However, these therapies induce complete vascular depletion leading to hypoxic niche, drug resistance, and tumor recurrence rate or leading to impaired delivery of chemo drugs and immune cell infiltration at the tumor site. Achieving a balance between oxygenation and tumor growth inhibition requires determining vascular normalization after treatment with a low dose of antiangiogenic agents. However, monotherapy within the approved antiangiogenic agents’ benefits only some tumors and their efficacy improvement could be achieved using immunotherapy and emerging nanocarriers as a clinical tool to optimize subsequent therapeutic regimens and reduce the need for a high dosage of chemo agents. More importantly, combined immunotherapies and nano-based delivery systems can prolong the normalization window while providing the advantages to address the current treatment challenges within antiangiogenic agents. This review summarizes the approved therapies targeting tumor angiogenesis, highlights the challenges and limitations of current therapies, and discusses how vascular normalization, immunotherapies, and nanomedicine could introduce the theranostic potentials to improve tumor management in future clinical settings.

Educational hub refers to centres of excellence in higher education and research whose aims are to provide high-quality education for both national and international students to enhance the competitiveness of the country. These educational hubs provide an opportunity for knowledge exchanges and innovation in local regions through education and training. In response to the COVID-19 pandemic, rapid shifts were made towards online learning in education around the world. Although the lockdown is over, remote learning will likely play an increasingly prominent role in education. The adoption of scaled remote learning during the pandemic provided evidence of the importance of online learning. They offer an insight into global society, helping prepare students for an increasingly interconnected world by facilitating links between different regions. Educational hubs can be tied to distance learning and are successful in attracting international students when offering a combination of distance learning methods and innovative programs. This paper examines the phenomenon of educational hubs in higher education for international education through online learning with digital technology. New opportunities for online and distance learning within the definition of educational hubs are analyzed, and three online and blended learning models that reflect the development of educational hubs based on COVID-19 conditions of education are offered. In addition, the successful cases and experiences of distance learning hubs in China and Iran in recent years are described.

Background and Objectives: Human rhinovirus (HRV), a major cause of common cold, was associated to the hospitalization of children and adults. This cross-sectional study aimed to determine the prevalence, and genotype distribution of HRV in the patients with mild to severe respiratory infections who were negative for SARS-Cov-2. Materials and Methods: Nasopharyngeal swab specimens (n = 356) from the patients aged 29 days to 82 years, received for the respiratory virus detection from January to December 2021, were analyzed for human rhinovirus (HRV) by RT- PCR. As a final step, genotyping was performed on obtained sequences. Results: A total of 37 HRV infections were identified (37/356, 10%). The highest rates of positive HRV tests were observed in February (21.6%), and January (18.9%), compared with June and August (0%). HRV-positive cases mainly appeared in winter. Among the age groups, those 2-55 years of age had the lowest detection rate (3%). Among HRV-positive samples, 30 (81%) were identified as type HRV-A, 5 (13.5%) as HRV-B, and 2 (5.5%) as HRV-C. Conclusion: Our results suggested that HRV frequency gradually decreased with the age of patients which is more active in Iran, especially in the cold months.

Abstract Background MDA-7/IL-24 cytokine has shown potent antitumor properties in various types of cancer without exerting any significant toxicity on healthy cells. It has also been proved to encompass pro-immune Th1 cytokine-like behavior. Several E7 DNA vaccines have developed against human papillomavirus (HPV)-related cervical cancer. However, the restricted immunogenicity has limited their clinical applications individually. To address this deficiency, we investigated whether combining the E7 DNA vaccine with MDA-7/IL-24 as an adjuvant would elicit efficient antitumor responses in tumor-bearing mouse models. Next, we evaluated how suppression of immunosuppressive IL-10 cytokine would enhance the outcome of our candidate adjuvant vaccine. Methods For this purpose, tumor-bearing mice received either E7 DNA vaccine, MDA-7/IL-24 cytokine or combination of E7 vaccine with MDA-7/IL-24 adjuvant one week after tumor challenge and boosted two times with one-week interval. IL-10 blockade was performed by injection of anti-IL-10 mAb before each immunization. One week after the last immunization, mice were sacrificed and the treatment efficacy was evaluated through immunological and immunohistochemical analysis. Moreover, the condition of tumors was monitored every two days for six weeks intervals from week 2 on, and the tumor volume was measured and compared within different groups. Results A highly significant synergistic relationship was observed between the E7 DNA vaccine and the MDA-7/IL-24 cytokine against HPV-16+ cervical cancer models. An increase in proliferation of lymphocytes, cytotoxicity of CD8+ T cells, the level of Th1 cytokines (IFN-γ, TNF-α) and IL-4, the level of apoptotic markers (TRAIL and caspase-9), and a decrease in the level of immunosuppressive IL-10 cytokine, together with the control of tumor growth and the induction of tumor regression, all prove the efficacy of adjuvant E7&IL-24 vaccine when compared to their individual administration. Surprisingly, vaccination with the DNA E7&IL-24 significantly reduced the population of Regulatory T cells (Treg) in the spleen of immunized mice compared to sole administration and control groups. Moreover, IL-10 blockade enhanced the effect of the co-administration by eliciting higher levels of IFN-γ and caspase-9, reducing Il-10 secretion and provoking the regression of tumor size. Conclusion The synergy between the E7 DNA vaccine and MDA-7/IL-24 suggests that DNA vaccines’ low immunogenicity can be effectively addressed by coupling them with an immunoregulatory agent. Moreover, IL-10 blockade can be considered a complementary treatment to improve the outcome of conventional or novel cancer therapies.

One of the causes of financial crisis is the formation of price bubbles. In the economic literature, the deviation of stock prices from their long-term equilibrium has been introduced as a bubble that causes instability in financial markets and may, in some cases, lead to stock market crash and economic recession. The purpose of this article is to study the process of price bubble formation in conventional financial markets and to prove the claim that in the Islamic financial market there are fewer grounds for this. For this purpose, after theoretically proving the claim using Generalized Sup Augmented Dickey–Fuller (GSADF) and ARMA method and estimating the risk function based on logistic regression, the bubble in the conventional and Islamic financial market of Indonesia was investigated. The results show that despite the price bubble in the conventional and Islamic financial markets, its average and standard deviation in the former is much lower than in the latter.

Identification of key factors affecting the self-directed learning process in the virtual environment of medical education is vital. In this article, we designed a model that describes the self-directed learning process in the virtual learning environment for post graduate students of medical sciences in Iran. This study was carried out in two steps: first, using a qualitative study, we explored the formation of a self-directed learning process in the virtual environment. Second, a review of the literature was conducted to identify the conceptual models. Finally, based on the results, a self-directed learning model for virtual learning was developed. A total of 25 people were research participants in the qualitative part, and individual interviews were conducted with both faculty members and students. There were 1,049 codes, 80 subcategories, 15 categories, and 5 themes extracted from the interviews and through analysis. The themes included (a) backgrounds and requirements, (b) support, discipline, and coordination of the educational system, (c) students’ effort to manage to learn, (d) efficiency, attractiveness, and organization of educational environments and context, and (e) personal excellence, growth, and development. The self-directed learning process in virtual environments consists of some elements and structures, and a description of the relationship between these elements can be the basis of educational planning to develop and compile an effective evaluation of this skill.

In peer observation of teaching, an experienced colleague in the educational environment of a faculty member observes the educational performance of that faculty member and provides appropriate feedback. The use of peer review as an alternative source of evidence of teaching effectiveness is increasing. However, no research has been done in the field of tool design and development to peer review in classrooms that use a learning management system (LMS). This study used mixed methods. In the qualitative stage, after studying sources and interviewing professors active in virtual education, a question bank was prepared and a 26-item initial questionnaire created. In the quantitative stage, the psychometric properties of the developed instruments, such as the face, content, and structural validity, were examined, and reliability tests were performed. IBM SPSS Statistics (Version 20) was used for analysis. Five categories, including content preparation, content presentation, effective interactions, motivation management, and support services, and 26 subcategories were determined to be effective indicators in peer observation in LMS-based classes in medical sciences. During content analysis, 9 items were removed due to lack of necessary criteria. Then, using principal component analysis and varimax rotation in the present mode )Watkins, 2018), 5 components with eigenvalues ​​higher than 1 were extracted, which explained a total of 70.55% of the total variance. The inter-cluster correlation coefficient (ICC) was 0.88. Thus, the peer observation measurement tool, designed with 17 expressions using the answer method “yes/no”, showed good validity and reliability. The research results demonstrate that the evaluation of virtual classes of professors by their peers is effective and that the results can be used in e-learning promotion plans.

Background and Objectives: Parvovirus B19 (B19V) is usually transmitted through respiratory tract, but can also be received through blood transfusion. This study evaluated the seroprevalence, DNA existence, and circulating genotypes of B19V in hemophilia patients. Materials and Methods: Serum samples of cases and controls were analyzed for B19V using ELISA and real-time PCR. Finally, obtained sequences were used for genotyping. Results: Among cases, 3% were anti-B19V IgM positive and 47% were anti-B19V IgG positive and B19V DNA was detected in 16% of them. However, among controls, 38% were anti-B19V IgG positive (P>0.05) and 5% were B19V DNA positive (P= 0.019). Also ~13% of cases were positive and all of controls were negative for IgG avidity test (P= 0.029). Viral load in case group was higher than control group (P = 0.037). Conclusion: Since hemophilia patients receive large amounts of blood factors, prevalence of B19V in these patients might be higher than normal subjects.

Abstract Background The expansion and metastasis of colorectal cancers are closely associated with the dynamic growth of cancer stem cells (CSCs). This study aimed to explore the possible effect of LXR (a regulator of glycolysis and lipid hemostasis) in the tumorgenicity of human colorectal CD133 cells. Methods Human HT-29 CD133+ cells were enriched by MACS and incubated with LXR agonist (T0901317) and antagonist (SR9243) for 72 h. Cell survival was evaluated using MTT assay and flow cytometric analysis of Annexin-V. The proliferation rate was measured by monitoring Ki-67 positive cells using IF imaging. The modulation of LXR was studied by monitoring the activity of all factors related to ABC transporters using real-time PCR assay and western blotting. Protein levels of metabolic enzymes such as PFKFB3, GSK3β, FASN, and SCD were also investigated upon treatment of CSCs with LXR modulators. The migration of CSCs was monitored after being exposed to LXR agonist using scratch and Transwell insert assays. The efflux capacity was measured using hypo-osmotic conditions. The intracellular content of reactive oxygen species was studied by DCFH-DA staining. Results Data showed incubation of CSCs with T0901317 and SR9243 reduced the viability of CD133 cells in a dose-dependent manner compared to the control group. The activation of LXR up-regulated the expression and protein levels of ABC transporters (ABCA1, ABCG5, and ABCG8) compared to the non-treated cells (p

The innovation management process still lacks the methodological foundations to deal with the turbulent and complex conditions of the future in various fields. One of the new and powerful methods for companies in this situation is scenario-based planning, using scenario planning in companies in the process of innovation management, to face the complex situation of businesses in the future and to predict market trends and information technology, identify and interpret alternative futures, Identifying weak signals and entering new markets is useful and necessary. Therefore, the present study intends to use the capacities and potentials of scenario planning in order to promote and improve innovation management. In the meantime, the qualitative approach and intuitive logic of scenario planning is very effective and efficient for managing innovation. The method of this research is case-contextual and strategically has a qualitative approach and according to the purpose, it is a fundamental research. A combination of documentary methods (library studies) and interviews with experts have been used to collect data. The study population is information technology companies and purposive sampling method has been used. In order to analyze the data, the method of "Grounded Theory" with Glaser "classical design" approach has been used. The product of data analysis in three stages of open, pivotal and selective coding, resulted in the identification of components in the form of an advanced scenario planning method for innovation management that provides valuable insights and knowledge for decision makers and managers.

Abstract Background Influenza virus infection is among the most detrimental threats to the health of humans and some animals, infecting millions of people annually all around the world and in many thousands of cases giving rise to pneumonia and death. All those health crises happen despite previous and recent developments in anti-influenza vaccination, suggesting the need for employing more sophisticated methods to control this malign infection. Main body The innate immunity modules are at the forefront of combating against influenza infection in the respiratory tract, among which, innate T cells, particularly gamma-delta (γδ) T cells, play a critical role in filling the gap needed for adaptive immune cells maturation, linking the innate and adaptive immunity together. Upon infection with influenza virus, production of cytokines and chemokines including CCL3, CCL4, and CCL5 from respiratory epithelium recruits γδ T cells at the site of infection in a CCR5 receptor-dependent fashion. Next, γδ T cells become activated in response to influenza virus infection and produce large amounts of proinflammatory cytokines, especially IL-17A. Regardless of γδ T cells’ roles in triggering the adaptive arm of the immune system, they also protect the respiratory epithelium by cytolytic and non-cytolytic antiviral mechanisms, as well as by enhancing neutrophils and natural killer cells recruitment to the infection site. Conclusion In this review, we explored varied strategies of γδ T cells in defense to influenza virus infection and how they can potentially provide balanced protective immune responses against infected cells. The results may provide a potential window for the incorporation of intact or engineered γδ T cells for developing novel antiviral approaches or for immunotherapeutic purposes.

Abstract Background Human papillomavirus (HPV)-associated malignancy remain a main cause of cancer in men and women. Cancer immunotherapy has represented great potential as a new promising cancer therapeutic approach. Here, we report Mesenchymal stem cells (MSCs) as a carrier for the delivery of oncolytic Newcastle disease virus (NDV) for the treatment of HPV-associated tumor. Methods For this purpose, MSCs obtained from the bone marrow of C57BL mice, then cultured and characterized subsequently by the flow cytometry analysis for the presence of cell surface markers. In this study, we sought out to determine the impacts of MSCs loaded with oncolytic NDV on splenic T cell and cytokine immune responses, caspase-3 and -9 expression, and myeloid and myeloid-derived suppressor cells (MDSCs) by histological and immunohistochemical studies in the tumor microenvironment (TME). Results Our findings proved that MSCs possess both migratory capacity and tumor tropism toward transplanted tumor tissue after peritumoral administration. Tumor therapy experiments indicated that oncolytic NDV delivered by MSCs-engineered system significantly reduces tumor growth, which is associated with the enhancement of E7-specific lymphocyte proliferation, CD8+ T cell cytolysis responses, and splenic IFN-γ, IL-4 and IL-12 responses compared with control groups. Moreover, the treatment upregulated the concentration of apoptotic proteins (caspase 9) and increased infiltration of tumor microenvironment with CD11b + myeloid and Gr1 + MDSCs cells. Conclusions Our data suggest MSCs carrying oncolytic NDV as a potentially effective strategy for cancer immunotherapy through inducing splenic Th1 immune responses and apoptosis in the tumor microenvironment.

Abstract Compared with conventional cancer treatments, the main advantage of oncolytic virotherapy is its tumor-selective replication followed by the destruction of malignant cells without damaging healthy cells. Accordingly, this kind of biological therapy can potentially be used as a promising approach in the field of cancer management. Given the failure of traditional monitoring strategies (such as immunohistochemical analysis (in providing sufficient safety and efficacy necessary for virotherapy and continual pharmacologic monitoring to track pharmacokinetics in real-time, the development of alternative strategies for ongoing monitoring of oncolytic treatment in a live animal model seems inevitable. Three-dimensional molecular imaging methods have recently been considered as an attractive approach to overcome the limitations of oncolytic therapy. These noninvasive visualization systems provide real-time follow-up of viral progression within the cancer tissue by the ability of engineered oncolytic viruses (OVs) to encode reporter transgenes based on recombinant technology. Human sodium/iodide symporter (hNIS) is considered as one of the most prevalent nuclear imaging reporter transgenes that provides precise information regarding the kinetics of gene expression, viral biodistribution, toxicity, and therapeutic outcomes using the accumulation of radiotracers at the site of transgene expression. Here, we provide an overview of pre-clinical and clinical applications of hNIS-based molecular imaging to evaluate virotherapy efficacy. Moreover, we describe different types of reporter genes and their potency in the clinical trials.

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.

Effective classroom management methods are well known, but effective ways of managing classes of beginner teachers remain elusive. Classroom management refers to the wide range of skills and techniques that teachers use to ensure that classes are conducted without destructive student behavior. The present study is applied nonexperimental research. The purpose of this study was to design a tool to measure the effective management of the virtual classroom from the perspective of professors and students in e-learning and evaluate its validity and reliability. The research sample was taken randomly from all universities that make use of e-learning in Tehran, Iran, during the 2019–2020 semesters. The results show that the professional development of online classroom management is necessary for preparing teachers to teach in digital environments. The results of this research in the form of a validated questionnaire can be considered as an indicator for educators and students working in online environments, and this tool can be used for effective teaching and learning in the digital age.

Although SARS-CoV-2 entry to cells strictly depends on angiotensin-converting enzyme 2 (ACE2), the virus also needs transmembrane serine protease 2 (TMPRSS2) for its spike protein priming. It has been shown that the entrance of SARS-CoV-2 through ACE2 can be blocked by cellular TMPRSS2 blockers. The main aim of this study was to find potential inhibitor(s) of TMPRSS2 through virtual screening against a homology model of TMPRSS2 using the library of marine natural products (MNPs). The homology modeling technique for generating a three-dimensional structure of TMPRSS2 was applied. Molecular docking, MM-GBSA and absorption, distribution, metabolism, excretion (ADME) evaluations were performed to investigate the inhibitory activity of marine natural products (MNPs) against TMPRSS2 and their pharmacokinetic properties. Camostat and nafamostat mesylate were used as the standard inhibitory molecules. Seven MNPs were able to inhibit TMPRSS2 better than the standard compounds. MNP 10 with CAS number 107503-09-3, called Watasenia β-D- Preluciferyl glucopyrasoiuronic acid, was found to be the best inhibitor of TMPRSS2 with acceptable pharmacokinetic properties. Herein, for the first time, a new marine natural product was introduced with potent inhibitory effects against TMPRSS2. MNP 10 exhibited favorable drug-like pharmacokinetic properties and it promises a novel TMPRSS2 blocker to combat SARS-CoV-2.

Background: At the beginning of the New Year 2020, China alerted the world health organization (WHO) to a cluster of unusual pneumonia cases in Wuhan. After extensive speculation, eventually a new species of coronavirus introduced as the causative pathogen of the disease. Coronavirus disease 2019 (COVID-19) is a name for the disease, and the virus that causes it is known SARS-CoV-2. The very rapid spread of the COVID-19 in China and in many other countries has caused fear among people across the world. The novel coronavirus outbreak declared a Public Health Emergency of International Concern on 30 January 2020. Materials and Methods: Several databases such as PubMed, Scopus, Google scholar, and BioRxiv were searched for publications reporting on the novel coronavirus up to 29 February 2020. Literature searches were performed using keywords including “Coronavirus 2019”, “2019-nCoV”, “COVID-19”, and “SARS-CoV-2”. Moreover, websites such as the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC) were searched to retrieve updated data and statistics regarding the novel coronavirus. We extracted data on the epidemiology, pathogenesis, virology, clinical manifestations, transmission routes, diagnosis, treatment, and prevention measures. Results: From the 1416 articles identified in the initial search, 53 were remained after title and abstract screening. After full-text review, 37 articles were eligible to include in our study. Incubation period for COVID-19 is between 2-10 days, according to the World Health Organization (WHO). The case fatality rate in patients infected with SARC-CoV-2 is 4.3%, and the results indicate that the mortality is higher in elderly individuals and patients with chronic conditions including patients with coronary artery disease, diabetes, chronic pulmonary disease, and hypertension. The mortality rate in healthy subjects is less than 1%. Conclusion: The outbreak caused by the novel coronavirus is larger than the previous human coronaviruses, showing that the SARS-CoV-2 is an extremely contagious virus. However, the mortality rate of COVID-19 is lower than that of other coronaviruses diseases such as SARS or MERS and other viruses like HIV and Ebola. Currently, due to the lack of an effective treatment and vaccine, the best way to deal with the COVID-19 disease is to prevent transmission and spread of the virus and to execute personal protective measures.

In this work, the dispersed phase holdup in a Kühni extraction column is predicted using intelligent methods and a new empirical correlation. Intelligent techniques, including multilayer perceptron and radial basis functions network are used in the prediction of the dispersed phase holdup. To design the network structure and train and test the networks, 174 sets of experimental data are used. The effects of rotor speed and the flow rates of the dispersed and continuous phases on the dispersed phase holdup are experimentally investigated, and then the artificial neural networks are designed. Performance evaluation criteria consisting of R2, RMSE, and AARE are used for the models. The RBF method with R2, RMSE, and AARE respectively equal to 0.9992, 0.0012, and 0.9795 is the best model. The results show that the RBF method well matches the experimental data with the lowest absolute percentage error (2.1917%). The rotor speed has the most significant effect on the dispersed phase holdup comparing to the flow rates of the continuous and dispersed phases.

Abstract Background The increased levels of blood cytokines is the main immunopathological process that were attributed to severe clinical outcomes in cases of influenza A, influenza B and people with influenza-like illness (ILI). Functional genetic polymorphisms caused by single nucleotide polymorphisms (SNPs) in inflammatory cytokines genes can influence their functions either qualitatively or quantitatively, which is associated with the possibility of severe influenza infections. The aim of the present case-control study was to investigate the association of polymorphisms in inflammatory cytokines genes with influenza patients and ILI group in an Iranian population. Methods Total number of 30 influenza B, 50 influenza A (H1N1) and 96 ILI inpatient individuals were confirmed by Real-time RT-PCR and HI assays. The genotype determination was assessed for defined SNPs in IL-1β, IL-17, IL-10 and IL-28 genes. Results The frequencies of the IL-1β rs16944 (P = 0.007) and IL-17 rs2275913 (P = 0.006) genotypes were associated with severe influenza disease, while the frequencies of IL-10 rs1800872 and IL-28 rs8099917 were not associated with the disease (P > 0.05). Also, the absence of A allele in IL-17 rs2275913 SNP increased the risk of influenza A (H1N1) infection (P = 0.008). Conclusions This study demonstrated that influenza A- (H1N1) and B-infected patients and also ILI controls have different profiles of immune parameters, and individuals carrying the specific cytokine-derived polymorphisms may show different immune responses towards severe outcome.

Abstract Oncolytic virotherapy has currently emerged as a promising approach upon which scientists have been able to induce tumor-specific cell death in a broad spectrum of malignancies. Paramyxoviruses represent intrinsic oncolytic capability, which makes them excellent candidates to be widely used in oncolytic virotherapy. The mechanisms through which these viruses destroy the cancerous cells involve triggering the autophagic machinery and apoptosis in target cells. Interestingly, oncolytic paramyxoviruses have been found to induce autophagy and lead to tumor cells death rather than their survival. Indeed, the induction of autophagy has been revealed to enhance the immunogenicity of tumor cells via the release of damage-associated molecular patterns (DAMPs) and the activation of autophagy-related immunogenic cell death (ICD). Subsequent cross-presentation of tumor-associated antigens (TAA) through the MHC-I complex to CD8+ T cells results in the productive priming of the tumor-specific immune response. In this review, we first briefly discuss autophagy and explain the process of viral xenophagy. Finally, we focus on the interactions between virus and autophagy proteins, elaborating on the global preclinical studies on oncolytic paramyxoviruses.

This article describes the practical implementation of parts of Teaching in a Digital Age: Guidelines for Designing Teaching and Learning by A.W. Bates (2015) in a course for educators in Austria and the development of medical education for universities in Iran. With the publication of the second edition of Teaching in a Digital Age in 2019, the authors show the impact of the book in training educators and developers of educational content. This note from the field emphasizes the benefits of making informed decisions about educational technologies using Bates’ (2015) SECTIONS model and of learning about massive open online courses (MOOCs) and how to work with them using his book.

The emergence of viral pneumonia caused by a novel coronavirus (CoV), known as the 2019 novel coronavirus (2019-nCoV), resulted in a contagious acute respiratory infectious disease in December 2019 in Wuhan, Hubei Province, China. Its alarmingly quick transmission to many countries across the world and a considerable percentage of morbidity and mortality made the World Health Organization recognize it as a pandemic on March 11, 2020. The perceived risk of infection has led many research groups to study COVID-19 from different aspects. In this literature review, the phylogenetics and taxonomy of COVID-19 coronavirus, epidemiology, and respiratory viruses similar to COVID-19 and their mode of action are documented in an approach to understand the behavior of the current virus. Moreover, we suggest targeting the receptors of SARS-CoV and SARS-CoV-2 such as ACE2 and other proteins including 3CLpro and PLpro for improving antiviral activity and immune response against COVID-19 disease. Additionally, since phytochemicals play an essential role in complementary therapies for viral infections, we summarized different bioactive natural products against the mentioned respiratory viruses with a focus on influenza A, SARS-CoV, MERS, and COVID-19.Based on current literature, 130 compounds have antiviral potential, and of these, 94 metabolites demonstrated bioactivity against coronaviruses. Interestingly, these are classified in different groups of natural products, including alkaloids, flavonoids, terpenoids, and others. Most of these compounds comprise flavonoid skeletons. Based on our survey, xanthoangelol E (88), isolated from Angelica keiskei (Miq.) Koidz showed inhibitory activity against SARS-CoV PLpro with the best IC50 value of 1.2 μM. Additionally, hispidulin (3), quercetin (6), rutin (8), saikosaponin D (36), glycyrrhizin (47), and hesperetin (55) had remarkable antiviral potential against different viral infections. Among these compounds, quercetin (6) exhibited antiviral activities against influenza A, SARS-CoV, and COVID-19 and this seems to be a highly promising compound. In addition, our report discusses the obstacles and future perspectives to highlight the importance of developing screening programs to investigate potential natural medicines against COVID-19.

Background: JC polyomavirus (JCV) is an epitheliotropic and neurotropic virus that identified in relationship with some devastating complications such as progressive multifocal leukoencephalopathy (PML) and linked to colorectal cancer. The aim of current study was to identify the prevalence of JCV in colorectal cancer for the first time in Iran. Methods: This retrospective case-control study was conducted by the hospitals affiliated to Iran University of Medical Sciences, Tehran, Iran from 2011 to 2016. Formalin-fixed paraffin-embedded (FFPE) blocks were used for DNA extraction by QIAamp® DNA FFPE Tissue Kit. The SYBER Green Real-time PCR assay performed by specific primers for JCV T-Large Ag. Melting curve analysis used for evaluation of amplification specificity. Positive control cloned in pTZ57R/T plasmid by Generay Biotechnology system. Results: Of 157 specimens 66 were colorectal cancer by the mean age (y) ± std. deviation 59.35±14.48 and 91 healthy control by the mean age (y) ± std. deviation 57.21±14.66. All 157 specimens tested for JCV T-Large Ag gene by Real-time PCR method and we found that there was not any positive result although the melting analysis showed specificity of positive control amplification. Conclusion: Low prevalence of JCV infection in Iranian CRC population confirmed by the current study results; there was not any JCV positive result in CRC and healthy control groups. Further studies by broader and different populations are recommended.

Conservation-restoration is an empirical science devoted to the preventive and remedial treatment of cultural heritage objects. At a professional level, it can be characterised as a blend of theoretical knowledge and practical skills. Although conservation-restoration originates from the historical accumulation of the skills of master craftsmen and artists, it has been developed into an academic field during the 20th century, having associations with a wide range of humanities and natural sciences, applied chemistry and physics, as well as analytical, organisational and philosophical elements.Recent studies of conservation-restoration are characterised by interdisciplinary approaches. Despite the discipline’s academic structure having remained intact, commonalities between conservation-restoration and other disciplines have resulted in further overlaps. Nowadays, multidisciplinary and interdisciplinary researches are developing at the boundaries of the scientific disciplines. In the present paper, boundaries, commonalities and collaborations between the conservation-restoration of monuments and other disciplines such as architecture, civil engineering, archaeology and social science, have been explained. Multi-specialism has its history in disciplines such as agriculture, industry and vocational training in Iran. However, when it comes to restoration, and despite the original multidisciplinary intentions in the design of BA courses in this field, the view towards curriculum is still predominantly single-disciplinary. The discipline’s isolation from other disciplines of similar nature such as architecture has generated obstacles for a useful teaching. The present study makes use of logical reasoning together with a review of the history of the pedagogy in the discipline from the beginning to the initiation of academic institutions. The main aim of this paper is to offer a correct description of the discipline, which is different from what is considered interdisciplinary or sub-disciplinary. To do so, attempts are made to analyse the curriculum content and its relation with other disciplines with close ties with restoration. The conclusion is that a restoration graduate is of a nature beyond one from architecture, structure, chemistry or sociology, and that this difference must be taken into account for planning the curriculum.

Background: Xenotropic murine leukemia virus-related virus (XMRV) is a gamma retrovirus, which has been detected in patients with prostate cancer, chronic fatigue syndrome, and general population with a number of acquired infections such as infection with human T-cell lymphotropic virus (HTLV) and human immunodeficiency virus (HIV). The aim of this study was to determine the HTLV-1 and XMRV coinfection for the first time in Iranian patients who were admitted to the Tehran hospitals. Materials and Methods: Two hundred and ninety one patients suspected with HTLV-1 were referred to the hospitals affiliated to the Iran University of Medical Sciences, Tehran, Iran from April 2012 to October 2016. Genomic deoxyribonucleic acid (DNA)/ribonucleic acid (RNA) from peripheral blood mononuclear cells/cerebrospinal fluids was extracted by High Pure Viral Nucleic Acid Kit (Roche, Germany). After complementary DNA synthesis, conventional reverse transcriptase polymerase chain reaction was used for the detection of HTLV-1 or XMRV-infected patients. Statistical Package for Social Sciences (SPSS) software, version 16 (SPSS, Chicago, IL, USA) was used for statistical analyses. Results: Of the 291 patients suspected of HTLV infection, 123 (42.3%) were male with a mean age of 38±15 years. HTLV-1 RNA was found in 93 (31.9%) specimens comprising 40 men (41.3%) and 53 women (56.9%). Of the 93 patients who were HTLV-1 positive, one sample (1%) was positive for XMRV env gene. Conclusion: These findings suggest that the lack of significant detection of XMRV in patients who were HTLV-1 positive could not be associated with complications of HTLV-1. Although this is a preliminary report from Iranian patients with HTLV-1, further studies are needed to show the actual prevalence of XMRV infection by geographical distribution and various populations.

Influenza epidemics and pandemics cause notable morbidity and mortality. Mortality cases are mostly associated with immunopathogenic mechanisms, although still poorly understood. Human studies help to understand the immunopathogenesis of influenza. However, there is limited information in this regard. Recent studies using experimental animal models have significantly improved our knowledge on complex mechanisms involved in the immunopathogenesis during influenza infections including acute inflammatory responses of neutrophils, dendritic cells, macrophages, toll-like receptors, chemokines, cytokines, CD4+ and CD8+ T cells. Due to influenza infection, elevated levels of cytokines and chemokines are produced during influenza-induced inflammation which are known as cytokine storm which is a severe immune response characterized by the recruitment of inflammatory leukocytes and increased levels of cytokines and chemokines at the site of infection. This review aimed to discuss the most recent findings on mechanisms of influenza immunopathogenesis.

The objective evidence of research in various domains shows that companies are in danger because of lack of a framework to address the ambiguous and complex situations of the future. Meanwhile, corporate foresight is trying to respond to this need. In this situation, companies are working to develop their innovations in order to create value and wealth. One of the new and powerful tools and methods for companies in this way is corporate foresight that improves and develops the innovation management process. The present study seeks to explore the capabilities and potentials of corporate foresight in order to improve and promote innovation management. In the meantime, it utilizes the appropriateness and capabilities of the scenario methodology. The research findings combine a quantitative analysis of structural equations that examine the effects of corporate foresight on innovation management with the qualitative method through a feedback process, referral to experts and content analysis. It is worth mentioning in the qualitative analysis that researchers could return to the previous stage or stages and review the course ahead in each of the semi-structured in-depth interviews with experts and content analysis them in order to achieve the indicators and components of the framework. Research findings include effective factors of corporate foresight on innovation management in the quantitative part and, along with this, provide a corporate foresight framework for the development and improvement of innovation management, and then the development of corporate foresight framework which is based on scenario for improving innovation management.

The Middle East respiratory syndrome coronavirus (MERS-CoV) as a causative agent of severe lower respiratory tract infection in humans, considered as a global threat, especially against to Persian Gulf countries. Since its discovery in 2012, MERS-CoV has spread 27 countries affecting about 1800 people and caused more than 600 deaths in worldwide. In comparison to SARS (severe acute respiratory syndrome), MERS-CoV appears to have a higher mortality rate (40% versus 10%) and is particularly more severe in patients with underlying medical conditions. Until now, the most MERS-CoV cases (more than 85 percent) have had a history of travel or residence in the Middle East countries. A possible intermediate host for MERS-CoV is camel. Clinical manifestations of MERS range from mild or asymptomatic disease to acute respiratory syndrome and multi-organ failure resulting in death, mostly in individuals with preexisting medical co-morbidities. There is no specific antiviral treatment for MERS and infection prevention and control practices are necessary to prevent spread of MERS-CoV in health care facilities. In present study, we have briefly outlined the recent information about the epidemiology, clinical features, diagnosis, treatment and prevention of MERS-CoV.

Gold nanoparticles (GNPs) have been recently applied for various diagnostic and therapeutic purposes. The unique properties of these nanoparticles (NPs), such as relative ease of synthesis in various sizes, shapes and charges, stability, high drug-loading capacity and relative availability for modification accompanied by non-cytotoxicity and biocompatibility, make them an ideal field of research in bio-nanotechnology. Moreover, their potential to alleviate various inflammatory factors, nitrite species, and reactive oxygen production and the capacity to deliver therapeutic agents has attracted attention for further studies in inflammatory and autoimmune disorders. Furthermore, the characteristics of GNPs and surface modification can modulate their toxicity, biodistribution, biocompatibility, and effects. This review discusses in vitro and in vivo effects of GNPs and their functionalized forms in managing various autoimmune disorders (Ads) such as rheumatoid arthritis, type 1 diabetes, and multiple sclerosis.

Rotavirus is associated with increased risk for severe diarrhea in infants and young children worldwide. This systematic review and meta-analysis was performed to determine the prevalence rate of rotavirus from different parts of Iran and provide an overall relative frequency (RF) for Iran. We performed a systematic literature review from several databases including PubMed, ISI Web of Science, Scopus, OVID, MAG IRAN, IranMedex, and Iranian Scientific Information Database. We searched the following keywords: “rotavirus,” “rotavirus infection,” “acute gastroenteritis,” “diarrhea,” “children,” “infant,” and “Iran.” The purpose of this study was to report the prevalence of rotavirus with the application of meta-analysis. We selected 43 researches out of 1147 for our study. From all the samples, the pooled estimate of prevalence (95% confidence interval) =39.9% (0.396%–0.409%) were rotavirus positive. It should be noted that rotavirus infection's RF varied from 6.4% to 79.3% in Birjand and Tehran Provinces, respectively. Thereupon, it is divergent in different studies. According to our study result, rotavirus RF has a wide range in Iran and is associated with diarrhea in children. Thus, further researches should be taken to minimize the emergence and transmission of rotavirus.

In this study, the extraction of phenol from wastewater was simulated using intelligent methods which include multi-layer perceptron, radial basis functions network, and support vector regression. To design the network structure and to train and test it, 184 experimental data sets were used. Inputs to the network consisted of organic–aqueous volume ratio, rotor speed, temperature, pH, and time while extraction efficiency was the output. Root mean square error and correlation coefficient were used in all the three models as network performance and network stop criteria. Comparison of the results obtained from the three models revealed that the support vector regression was the best model with a correlation coefficient of 0.684 and a root mean square error of 0.99. Moreover, model results showed good agreement with experimental data. Optimal process operational parameters included an organic to aqueous volume ratio of 0.22, a rotor speed of 350 rpm, a temperature of 22.86 °C, a pH equal to 7.5, and an agitation time of 15.86 minutes; the corresponding extraction efficiency was obtained to be 96.35.

An amendment to this paper has been published and can be accessed via the original article.

An amendment to this paper has been published and can be accessed via the original article.

Annual influenza vaccination is the best means of prevention and control of influenza virus infection and its complications. Efforts to increase influenza vaccines coverage, especially in high-risk groups including young children, the elderly, pregnant women and immunocompromised individuals have led to substantial reduction in health burden, severity and duration of infection. This review will focus on vaccination coverage against influenza infection among different population groups in Iran. Also, available evidence suggesting the effectiveness and adverse effects of currently licensed influenza vaccines will be discussed.

We previously developed an influenza virus like particle with HA, M, and NA proteins using Bac-to-Bac expression system and SF9 cell line. To evaluate the immunogenicity of our construct, we assessed the humoral, cytokine induced by H1N1-VLP in BALB/c mice immunized intranasally and intramuscularly. Enzyme-linked immunosorbent assay and Relative quantitative real-time PCR were used to evaluate the antibody (IgG and IgA) and mRNA levels of IL-6, IL-4, IL-10 and IFN-g in PBMCs. Our results showed that VLP was capable of intranasal (I.N.) and intramuscular (I.M.) induction of serum IgG and IgA responses. Interestingly, I.N. route induced higher IgG and IgA titer than I.M. route, which was statistically significant. Moreover, mRNA levels of IL-6 (4.2-4.5 folds), IFN-g (5.5-5.7 folds), and the anti-inflammatory cytokine IL-10 (2.5-3 folds) and IL-4 (2.4-2.8 folds) were significantly elevated in mice immunized I.N. and I.M. with H1N1-VLP compared to the control group. Our findings indicated that a non-infectious genome-less VLP approach mimics parenteral virus with multiple viral antigens and epitopes that stimulate a diverse set of immune responses such as innate immunity, specific serum IgG antibody, cell-mediated immunity, and local antibodies.

After publication of this article [1], it was brought to our attention that there are some errors in the section of ‘Authors’ contributions’.

In this study, the appropriateness of existing quality standards and their use in practice in educational organizations were discussed. The study shows how the quality standard of TQM and QMTL and the possibility of their articulation to develop a holistic model can contribute to change this situation. The study alsoinvestigated whether this standard is an adequate basis for quality development in organizations. To implement a quality system in an educational organization, four main steps are necessary: context setting, model adaptation, model implementation/adoption, and quality development. Each step should be performed with a broad range of actors to raise awareness and consensus. To facilitate this process and to develop a quality system for an organization, the use of the holistic model for the description of quality approaches was recommended. Since the model is very generic, more research is necessary, especially to find specific solutions to different contexts of usage (e.g., for schools). Additionally, research has been initiated to analyze the differences and adaptation requirements for different countries and regions to include cultural aspects. Finally, a variety of tools is being developed to support this process, such as the initial choice of a quality approach or the choice of quality instruments. For the future, it can be expected that a variety of tools will be available to support this process and to integrate quality into a broad range of educational organizations.