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Background: Lassa fever is an acute viral haemorrhagic disease caused by the Lassa virus (LASV). It is endemic in West Africa and infects about 300,000 people each year, leading to approximately 5000 deaths annually. The development of the LASV vaccine has been listed as a priority by the World Health Organization since 2018. Considering the accelerated development and availability of vaccines against COVID-19, we set out to assess the prospects of LASV vaccines and the progress made so far. Materials and Methods: We reviewed the progress made on twenty-six vaccine candidates listed by Salami et al. (2019) and searched for new vaccine candidates through Google Scholar, PubMed, and DOAJ from June to July 2021. We searched the articles published in English using keywords that included "vaccine" AND "Lassa fever" OR "Lassa virus" in the title/. Results: Thirty-four candidate vaccines were identified - 26 already listed in the review by Salami et al. and an additional 8, which were developed over the last seven years. 30 vaccines are still in the pre-clinical stage while 4 of them are currently undergoing clinical trials. The most promising candidates in 2019 were vesicular stomatitis virus-vectored vaccine and live-attenuated MV/LASV vaccine;both had progressed to clinical trials. Conclusions: Despite the focus on COVID-19 vaccines since 2020, LASV vaccine is under development and continues to make impressive progress, hence more emphasis should be put into exploring further clinical studies related to the most promising types of vaccines identified.
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Introduction: Covid-19 epidemic results from an infection caused by SARS-CoV2. Evolution-based analyses on the nucleotide sequences show that SARS-CoV2 is a member of the genus Beta-coronaviruses and its genome consists of a single-stranded RNA, encoding 16 proteins. Among the structural proteins, the nucleocapsid is the most abundant protein in virus structure, highly immunogenic, with sequence conservatory. Due to a large number of mutations in the spike protein, the aim of this study was to investigate bioinformatics, expression of nucleocapsid protein and evaluate its immunogenicity as an immunogenic candidate. Materials and Methods: B and T cell epitopes of nucleocapsid protein were examined in the IEDB database. The PET28a-N plasmid was transferred to E. coli BL21(DE3) expression host, and IPTG induced recombinant protein expression. The protein was purified using Ni-NTA column affinity chromatography, and the Western blotting method was utilized to confirm it. Finally, mice were immunized with three routes of purified protein. Statistical analysis of the control group injection and test results was carried out by t-test from SPSS software. Results: The optimized gene had a Codon adaptation index (CAI) of 0/97 Percentage of codons having high- frequency distribution was improved to 85%. Expression of recombinant protein in E. coli led to the production of BoNT/B-HCC with a molecular weight of 45 kDa. The total yield of purified protein was 43 mg/L. Immunization of mice induced serum antibody response. Statistical analysis showed that the antibody titer ratio was significantly different compared to the control sample and the antibody titer was acceptable up to a dilution of 1.256000. Conclusion: According to the present study results, the protein can be used as an immunogenic candidate for developing vaccines against SARS-CoV2 in future research.
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This special issue contains 23 articles that discuss various aspects of antiviral research, focusing on the contributions and legacy of Dr. Mike Bray, the retiring Editor-in-Chief of Antiviral Research. The articles cover a range of topics, including the underappreciated mouse model for Ebola virus disease, the history and impact of the mouse-adapted Ebola virus model, and the characterisation of CD-1 mice infected with different strains of Ebola virus. Other articles delve into transplacental vertical transmission of flaviviruses, the development of reverse genetic systems for SARS-CoV-2, and the mechanisms of action and drug resistance of nucleotide analogues against the virus. The special issue also explores therapeutics for flaviviral infections, alternative splicing in RNA virus infections, and targeted protein degradation as an antiviral approach.
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Fructus Aurantii (FA) is the dry and immature fruit of Citrus aurantium L. and its rutaceous cultivars. FA has been widely used to treat digestive system diseases since ancient China, and it promotes gastrointestinal (GI) motility in functional dyspepsia (FD), but its potential therapeutic mechanisms remain unclear. We examined the effects of FA ethanol extracts in an iodoacetamide (IA)-induced FD rat model. Firstly, key FA therapy targets for FD were gathered using systematic pharmacology. Combined with systemic pharmacological analyses, plasma metabolomics based on UPLC-QTOF-MS were conducted. Then, MetaboAnalyst was used to jointly analyze systemic pharmacology targets and metabolomic metabolites to select key metabolic pathways. Finally, the key path is verified by experiments. FA exerted distinct therapeutic effects in anti-inflammation and promoting gastrointestinal motility in our IA-induced FD rat model. When compared with the model group, FA down-regulated the inflammatory factors interleukin 1beta and tumor necrosis factor-a. At the same time, FA up-regulated tight junction proteins in the intestinal epithelial barrier. Through the integrated analysis of metabolomics and systemic pharmacology, we conducted experimental verification on Fc epsilon RI signaling pathway. When compared with the model group, FA down-regulatedphospho-mitogen activated protein kinase, phospho-extracellular signal regulated kinase1/2, myosin light chain kinase, and phospho-myosin regulatory light chain protein levels. Thus, FA ameliorated FD by regulating the Fc epsilon RI signaling pathway. Our integrated strategy identified underlying FA mechanisms toward FD treatment and provided a foundation for FA development as a clinical agent for FD.
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This journal issue includes 31 articles that discuss salt stress in plants and amelioration strategies;algal biorefinery;in-silico docking studies of selected phytochemicals against papain like protease of SARS-Cov-2;development of an effective strategy using green synthesized nanoparticles;effect of methyl jasmonate in enhanced growth, antioxidants and reduced Pb uptake in contrasting cluster bean cultivars;biosynthesis of silver nanoparticles using mushroom extract and its toxicity assessement in zebrafish embryos;phytogenic synthesis of metallic nanoparticles;abiotic stress responses and strategies of microbes mediated mitigation for sustainable agriculture.
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The issues of practicality in using perfluorocarbon gas transport emulsions (or pure perfluorocarbons) in severe virus-associated pneumonia treatment were considered, including those caused by coronavirus infection. Perfluorocarbons are fully fluorinated carbon compounds, on the basis of which artificial blood substitutes have been developed - gas transport perfluorocarbon emulsions for medical purposes. Perfluorocarbon emulsions were widely used in the treatment of patients in critical conditions of various genesis at the end of the last-the beginning of this century, accompanied by hypoxia, disorders of rheological properties and microcirculation of blood, perfusion of organs and tissues, intoxication, and inflammation. Large-scale clinical trials have shown a domestic plasma substitute advantage based on perfluorocarbons (perfluoroan) over foreign analogues. It is quite obvious that the inclusion of perfluorocarbon emulsions in the treatment regimens of severe virus-associated pneumonia can significantly improve this category's treatment results after analyzing the accumulated experience. A potentially useful area of therapy for acute respiratory distress syndrome is partial fluid ventilation with the use of perfluorocarbons as respiratory fluids as shown in the result of many studies on animal models and existing clinical experience. There is no gas-liquid boundary in the alveoli, as a result of which, there is an improvement in gas exchange in the lungs and a decrease in pressure in the respiratory tract when using this technique, due to the unique physicochemical properties of liquid perfluorocarbons. A promising strategy for improving liquid ventilation effectiveness using perfluorocarbon compounds is a combination with other therapeutic methods, particularly with moderate hypothermia. Antibiotics, anesthetics, vasoactive substances, or exogenous surfactant can be delivered to the lungs during liquid ventilation with perfluorocarbons, including to the affected areas, which will enhance the drugs accumulation in the lung tissues and minimize their systemic effects. However, the indications and the optimal technique for conducting liquid ventilation of the lungs in patients with acute respiratory distress syndrome have not been determined currently. Further research is needed to clarify the indications, select devices, and determine the optimal dosage regimens for perfluorocarbons, as well as search for new technical solutions for this technique.
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Discovered in late 2019 in a market in the city of Wuhan, Hubei Province, China, SARS-CoV-2 is an important member of the Coronaviridae family, responsible for bringing the whole world into a state of alert causing a global pandemic. The virus has been identified as causing a characteristic clinical condition known as "Corona-virus disease 2019" (COVID-19), causing an Acute Respiratory Syndrome. Being a respiratory virus, transmitted by direct contact with an infected person and by touching contaminated surfaces, SARS-CoV-2 quickly spread throughout the world, causing a pandemic, having today more than 535 million people infected and causing more than million deaths. In addition to the respiratory system, the virus is present in other cells in the body. Findings show the presence of SARS-CoV-2 in cerebrospinal fluid associated with changes in the expression of neuronal inflammation markers, as well as an increased expression of cytokines released by astrocytes, indicating an alteration in the Central Nervous System (CNS). In this project, we analyzed the effects of SARS-CoV-2 infection directly on astrocytes, glial cells that are extremely important for the maintenance of homeostasis and CNS defense. Therefore, we produced astrocytes from three human iPSC strains to verify aspects of cell morphology and physiology, as well as gene and protein expression, after infection with the virus. We found that SARS-CoV-2 is capable of infecting astrocytes, but some studies are still needed to better elucidate its role in the interaction with this cell type in the CNS.
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The susceptibility of animal species to SARS-CoV-2, under experimental conditions, is a subject of great interest for the international scientific community. Compared to observational studies of natural disease outbreaks in different animal species, experimental studies based on in silico, in vitro and in vivo research, are important alternatives to evaluate the prediction of potential hosts for SARS-CoV-2 infection. In order to determine the susceptibility of a host species and the risk of acting as a potential animal reservoir, a large number of different animal species, domestic and wild, were experimentally infected with SARS-CoV-2, which were classified as permissive or resistant. Experimental infections have proven to be crucial for clarifying aspects of the pathogenetic mechanism, viral persistence and elimination, immune response, antiviral sensitivity, vaccine production, immunotherapy and improving diagnostic methods. In this article, some experimental infections carried out in different animal species will be reviewed, according to the data from the literature.
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In general, B and T lymphocytes, which are involved in adaptive immunity, are in charge of cell-mediated response and antibody-mediated immunity, respectively. Another subset of lymphocytes, known as natural killer (NK) cells, are innate effector cells. They serve as the body's initial line of defence against viral infections. They perform the task of eliminating stressed cells and are crucial for tumour immunity. These cells are capable of performing their killing function without clonal expansion and differentiation following activation. The NK cells will immediately eliminate infected host cells but other lymphocytes need lymphocyte proliferative response which takes several days and further differentiate into effector cells, so that they eliminate host cells infected by the viral pathogen. The NK cells also form a bridge between the adaptive and innate immunity and play significant roles during respiratory infection. Number and the role of NK cells correlate with the severity of severe acute respiratory syndrome (SARS);the number and the percentage of CD158b+ NK cells in severe SARS infection were significantly less in number than those with mild cases. Innate defence mechanisms, particularly NK cells, are able to control SARS infection even in the absence of T cells and antibodies, according to cellular immunological responses to SARS infection in mice. As a result, NK cells are crucial in the fight against viral infections of the respiratory system. As an innate immune system, they serve as the initial line of virus protection. It is possible to do additional research to take advantage of this NK cell trait and develop a cutting-edge therapeutic approach to fight developing respiratory viral diseases.
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The role of dietary fiber in highland barley in lowering blood lipids has been continuously studied in recent years. However, its effects on diabetes and diabetic nephropathy are rarely studied. Considering that highland barley bran is rich in dietary fiber, the effective use of dietary fiber in highland barley bran can not only alleviate the symptoms of diabetes but also improve the local economy. This article aimed to study the effects of highland barley fiber-rich powder (T-fiber) with a high-quality natural dietary fiber ratio (insoluble fiber/soluble fiber = 3 : 1) on the symptoms of hyperglycemia in a diabetic mouse model. Compared with the model group's blood glucose level (30.80 mmol/L), glucose tolerance (28.57 mmol/L), and glycosylated serum protein (2.43 mmol/L), T-fiber presented significant reductions in blood glucose (23.69 mmol/L), better glucose tolerance (21.32 mmol/L), and glycosylated serum protein (1.78 mmol/L) in the diabetic mouse model. Meanwhile, T-fiber effectively alleviated hepatocellular lesions. In addition, T-fiber not only improved kidney function by reducing the 24-hour urine output (8.25 ml), urine protein levels (11.51 mg), and serum creatinine (13.80 mol/L) but also alleviated renal pathology, including glomerular hypertrophy, mesangial expansion, and fibrosis. The above results proved the ability of T-fiber to reduce blood glucose and alleviate liver and renal function in diabetic mice. Altogether, T-fiber is a capable formula for utilizing highland barley bran dietary fiber, which alleviates diabetes symptoms and endows highland barley with promising value.
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This special issue includes 15 articles that discuss the mutagenic effect of tobacco smoke on male fertility;environmental and occupational exposure of metals and female reproductive health;free radical biology in neurological manifestations;paternal factors in recurrent pregnancy loss;mechanical dependency of the SARS-CoV-2 virus and the renin-angiotensin-aldosterone (RAAS) axis;a perspective review on medicinal plant resources for their antimutagenic potentials;asystematic review and meta-analysis of the impacts of glyphosate on the reproductive hormones;impact of ginseng on neurotoxicity induced by cisplatin in rats.
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This paper describes the pathogenesis and immunology of Macaca mulatta, Macaca fascicularis, ferrets, Syrian golden hamsters (Mesocricetus auratus), mice, cats, mink, pigs and rabbits used as models for SARS-CoV-2 infection.
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The eyes, which were not previously the subject of investigation, have emerged as one of the more intriguing aspect of COVID-19 infection. The probable pathways for SARS-CoV-2 infection through the eyes are either through the tear film and draining tear ducts leading to the upper respiratory tract and gastrointestinal tract, or through the conjunctiva into limbal superficial cells into the inner eye, where distribution via the blood or nervous system appears to be possible. Virus pathogenesis through tear and conjunctiva has been established in animal models of several coronavirus eye diseases, and preliminary research have shown that SARS-CoV-2 may do the same in humans. Given that COVID-19 cases have reached pandemic proportions and are on the rise, it is vital to recognize the illness's ocular manifestations and avert potentially vision-threatening effects. Coronaviruses may be transmitted between animals and humans through evolution, therefore investigating them in animal models could be crucial in the future to discover further elements of ocular involvement. It is recommended that health care and individual personnel take steps to avoid infection and limit viral transmission. More study is needed to understand the transmission pathways and the alternatives for COVID-19 prevention and therapy disseminated through the ocular surfaces for prompt recovery of the patients.
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In this review we summarize the current data about the etiopathogenesis of the virus myocarditis and inflammatory cardiomyopathy. Knowledge gaps, available experimental models and future directions are discussed. Unclear questions about the cardiovascular effects associated with COVID-19 infection are commented. This review is based on the latest published data of European, American and Japanese Heart Failure Association from 2021.
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Objective: To explore the antiviral effect of baricitinib in the SARS-CoV-2 infection and influence on cytokine levels.
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[Objective] At present, a novel emerging Coronavirus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has caused an epidemic in the world, seriously threatening human life and health. To establish a basis for a rapid detection method for SARS-CoV-2, the monoclonal antibodies targeting nucleocapsid (N)gene were prepared and identified in this study. [Methods] BA LB/c mice were immunized with purified SARS-CoV-2 N recombinant protein. After four times of immunization. the spleen cells of the mice were fused with SP2/0 myeloma cells. The positive hybridoma cell lines stably secreting monoclonal anti-body were screened through ELISA, and the reactivity of the monoclonal antibody was further determined by western blot and indirect immunofluorescence assay. [Results] After three subclones, two hybridoma cell lines designated as 2D11 and 8G6 were obtained. and the prepared antibodies showed good reactivity with the eukaryotic expression of SARS-CoV-2 N protein. [Conclusion] The monoclonal antibody manufactured in this study can be used for SARS-CoV-2 detection.
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This journal issue includes 48 articles that discuss development and validation of a novel quality assessment tool to measure the quality of nutrition information online;longitudinal association between takeaway food environment and secondary school adolescents BMI and body fat percentage;dietary practices, beliefs, and behaviours among adults with inflammatory bowel disease;postpartum depression in Irish mothers and associations with infant feeding practices;the impact of dietary saturated fat replacement with unsaturated fat on the plasma lipidome and cardiometabolic disease risk;ole of brain serotonin in age-related decline in physical activity in mice;ey stakeholder perceptions of food allergies within the airline industry;sleep quality of higher education students during COVID-19 and its association with diet quality and lifestyle behaviours.
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Objective: To investigate the molecular mechanism of the action by which the MERS-CoV E proxein induces autophagy in 293T cells.
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Since the outbreak of the new crown pneumonia, the new coronavirus (SARSCoV-2) has been mutating continuously, and it has now become prevalent in more than 200 countries. The cumulative number of confirmed cases in the world has exceeded 460 million, and the number of deaths has exceeded 6 million. The rapid mutation of SARS-CoV-2 highlights the importance of preventive and therapeutic drugs, however, effective therapeutic drugs for new coronary pneumonia are still very scarce. It is still the common goal of scientists from all over the world to develop a safe and effective drug for the treatment of new coronary pneumonia that can inhibit the infection of multiple SARS-CoV-2 mutant strains.
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Stress such as uncertainty about the future, including the problem of new coronavirus infection, is a very serious problem not only for physical health but also for mental health. It is certain that stress is one of the risk factors for developing mental disorders. We have found stress-responsive biomarker (stress marker) candidates through studies on the process from stress to disease onset. Recently, we have been trying to prove the stress-suppressing effect of aroma with brain factors. We analyzed how aroma affects behavioral changes due to stress and the expression of stress marker candidates in the brain. In this article, the data on aroma that we have accumulated so far will be introduced. Specifically, we will describe changes happened in experimental animals when they smelled coffee beans, lavender, cypress, a-pinene, and thyme linalool. When considering the biological effects of aroma, it is inevitable that not only the olfactory pathway but also odor molecules act through the bloodstream by nasal and transdermal absorption. The brain transferability of odor molecules may be a bottleneck in analyzing the biological effects of volatile components. Thus, we would like to discuss on this issue.