Myocarditis due to COVID-19 in a pediatric patient

Current knowledge about the COVID-19 pandemic is still limited, especially in the pediatric age group. So far, children are considered to be a minimally affected population;however, physicians from different parts of the world have recognized a new pediatric multi-systemic inflammatory syndrome, that provokes a multiple organ dysfunction, from which the heart is not exempted. The direct action of the virus on myocardial cells, as well as the cytokines storm -triggered by the infection- are responsible for the myocarditis developed in these patients. In this article a case with criteria of myocarditis associated with COVID-19 is described. Achieving an early diagnosis ofmyocarditis secondary to SARS-CoV-2 infection in the current epidemiological context allows a correct and timely therapeutic approach, avoiding the torpid evolution and fatal outcome of this disease, as well as other long-term complications.

Psychopharmacological assessment of antidepressant-like, anxiolytic, and sedative-hypnotic effects of tilia platyphyllos scop. Extract using experimental animal models

The prevalence of psychiatric disorders namely depression, anxiety, and sleep disturbances has been increased worldwide, particularly during the COVID-19 pandemic. In this regard, the interest of recent investigations is moved toward phytomedicines and bioactive substances derived from natural sources. Although Tilia platyphyllos Scop. contains high amounts of phenolic compounds such as quercetin, kaempferol, and catechin, there is no study on the possible effects of its extract on psychological disorders. The present study was carried out to determine the antidepressant-like, anxiolytic, and sedative-hypnotic effects of the hydroethanolic extract of T. platyphyllos leaves using forced swimming test (FST), tail suspension test (TST), elevated plus maze test (EPMT), pentobarbital-induced loss of righting reflex test and open field test (OFT). Following the ethanolic extraction of T. platyphyllos leaves, the extraction yield was 14% and the total phenolic and total flavonoid contents were found to be 135.23 +/- 0.14 mg gallic acid equivalent/g dry extract and 19.02 +/- 0.03 mg rutin equivalent/g dry extract, respectively. Both FTS and TST revealed a significant antidepressant-like activity for the tested extract at 400 mg/kg compared to the control group. In addition, the anxiolytic activity of the extract was proven through OFT and EPMT in the same dose. Finally, T. platyphyllos extract at 200 mg/kg and 400 mg/kg significantly increased the sleeping time when compared to the control group reflecting its potential hypnotic activity. Co-administration of T. platyphyllos extract at 400 mg/kg and flumazenil as the GABA-A receptor antagonist decreased the sleeping time but the observed effect was not statistically significant. Therefore, we cannot completely rule out the GABA-A receptor's involvement in the hypnotic activity of the extract. The biological results presented here led us to conclude that T. platyphyllos extract can be a prominent source of antidepressant, anxiolytic and hypnotic agents. Probably, the main phenolic compounds of T. platyphyllos such as quercetin, kaempferol, and catechin are involved in the observed effects. However, there is still a great need for additional investigations on the exact mechanisms.Copyright © 2022, Iranian Association of Pharmaceutical Scientists. All rights reserved.

Special Issue: Honor of Dr. Mike Bray on his retirement as the editor-in-chief of antiviral research. (Special Issue: Honor of Dr. Mike Bray on his retirement as the editor-in-chief of antiviral research.)

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.

[Antiviral activity of basidial fungus Inonotus obliquus aqueous extract against SARS-CоV-2 virus (Coronaviridae: Betacoronavirus: Sarbecovirus) in vivo in BALB/c mice model].

INTRODUCTION: The COVID-19 pandemic combined with seasonal epidemics of respiratory viral diseases requires targeted antiviral prophylaxis with restorative and immunostimulant drugs. The compounds of natural origin are low-toxic, but active against several viruses at the same time. One of the most famous compounds is Inonotus obliquus aqueous extract. The fruit body of basidial fungus I. obliquus is called Chaga mushroom. The aim of the work ‒ was to study the antiviral activity of I. obliquus aqueous extract against the SARS-CoV-2 virus in vivo. MATERIALS AND METHODS: Antiviral activity of I. obliquus aqueous extract sample (#20-17) was analyzed against strain of SARS-CoV-2 Omicron ВА.5.2 virus. The experiments were carried out in BALB/c inbred mice. The SARS-CoV-2 viral load was measured using quantitative real-time PCR combined with reverse transcription. The severity of lung tissue damage was assessed by histological methods. RESULTS: The peak values of the viral load in murine lung tissues were determined 72 hours after intranasal inoculation at dose of 2,85 lg TCID50. The quantitative real-time PCR testing has shown a significant decrease in the viral load compared to the control group by 4,65 lg copies/ml and 5,72 lg copies/ml in the lung tissue and nasal cavity samples, respectively. Histological methods revealed that the decrease in the number and frequency of observed pathomorphological changes in murine lung tissues depended on the introduction of the compound under study. CONCLUSION: The results obtained indicate the possibility of using basidial fungus Inonotus obliquus aqueous extract as a preventive agent against circulating variants of SARS-CoV-2 virus.

De Novo Human Angiotensin-Converting Enzyme 2 Decoy NL-CVX1 Protects Mice From Severe Disease After Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

The emergence of novel variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) underscores the need to investigate alternative approaches to prevent infection and treat patients with coronavirus disease 2019. Here, we report the preclinical efficacy of NL-CVX1, a de novo decoy that blocks virus entry into cells by binding with nanomolar affinity and high specificity to the receptor-binding domain of the SARS-CoV-2 spike protein. Using a transgenic mouse model of SARS-CoV-2 infection, we showed that a single prophylactic intranasal dose of NL-CVX1 conferred complete protection from severe disease following SARS-CoV-2 infection. Multiple therapeutic administrations of NL-CVX1 also protected mice from succumbing to infection. Finally, we showed that infected mice treated with NL-CVX1 developed both anti-SARS-CoV-2 antibodies and memory T cells and were protected against reinfection a month after treatment. Overall, these observations suggest NL-CVX1 is a promising therapeutic candidate for preventing and treating severe SARS-CoV-2 infections.

Aerosolized sulfated hyaluronan derivatives prolong the survival of K18 ACE2 mice infected with a lethal dose of SARS-CoV-2.

Despite several vaccines that are currently approved for human use to control the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there is an urgent medical need for therapeutic and prophylactic options. SARS-CoV-2 binding and entry in human cells involves interactions of its spike (S) protein with several host cell surface factors, including heparan sulfate proteoglycans (HSPGs), transmembrane protease serine 2 (TMPRSS2), and angiotensin-converting enzyme 2 (ACE2). In this paper we investigated the potential of sulphated Hyaluronic Acid (sHA), a HSPG mimicking polymer, to inhibit the binding of SARS-CoV-2 S protein to human ACE2 receptor. After the assessment of different sulfation degree of sHA backbone, a series of sHA functionalized with different hydrophobic side chains were synthesized and screened. The compound showing the highest binding affinity to the viral S protein was further characterized by surface plasmon resonance (SPR) towards ACE2 and viral S protein binding domain. Selected compounds were formulated as solutions for nebulization and, after being characterized in terms of aerosolization performance and droplet size distribution, their efficacy was assessed in vivo using the K18 human (h)ACE2 transgenic mouse model of SARS-CoV-2 infection.

Modeling the Tumor Microenvironment and Cancer Immunotherapy in Next-Generation Humanized Mice.

Cancer immunotherapy has brought significant clinical benefits to numerous patients with malignant disease. However, only a fraction of patients experiences complete and durable responses to currently available immunotherapies. This highlights the need for more effective immunotherapies, combination treatments and predictive biomarkers. The molecular properties of a tumor, intratumor heterogeneity and the tumor immune microenvironment decisively shape tumor evolution, metastasis and therapy resistance and are therefore key targets for precision cancer medicine. Humanized mice that support the engraftment of patient-derived tumors and recapitulate the human tumor immune microenvironment of patients represent a promising preclinical model to address fundamental questions in precision immuno-oncology and cancer immunotherapy. In this review, we provide an overview of next-generation humanized mouse models suitable for the establishment and study of patient-derived tumors. Furthermore, we discuss the opportunities and challenges of modeling the tumor immune microenvironment and testing a variety of immunotherapeutic approaches using human immune system mouse models.

Covid-19 Era in the Coastal Areas: The Cookies Formulation Gonad of Diadema setosum and its Impacts on Malnutrition During Infection

Infection with Salmonella typhi bacteria during the COVID-19 era has the potential to worsen malnutrition in children in low- and middle-income nations, particularly around the coast. Recent studies have demonstrated that one of the best strategies for preventing malnutrition is consuming local food sources from the sea, which are easy to acquire, inexpensive, and high in nutrients. In this study, 15 male mice were used as the test subjects. They were split into two groups: the intervention group and the control group, both before and after intraperitoneal injection of Salmonella typhi. The intervention group was given dosages of cookies containing Diadema setosum gonad (0.40 mg/kg of body weight), whereas the control group received only a natural diet. The blood samples were then analyzed to measure their hemoglobin levels using the Sahli haemometer method, and serum albumin concentrations were determined using the bromocresol green method. The results show that the treatment with Diadema setosum gonad cookies had a significant effect on the levels of albumin and hemoglobin (Hb), as well as the body weights of the intervened mice, with a statistically significant increase (p<0.05). Conversely, BALB/c mice in the control group demonstrated a decrease in their initial food intakes, resulting in a significant reduction in body weight, albumin, and hemoglobin (Hb). This finding implies that the cookie formula with Diadema setosum gonad as the principal ingredient has potential benefits in lowering the incidence of malnutrition for children. © 2023 The Author(s). Published by Enviro Research Publishers.

Preparation and identification of broad-spectrum monoclonal antibodies against N protein of avian infectious bronchitis virus

[Objective] To prepare broad-spectrum monoclonal antibody against N protein of avian infectious bronchitis virus (IBV), so as to lay a foundation for identifying conservative domain epitope of N protein and establish a universal IBV detection method. [Method] N protein of GX-YL5, a representative strain of IBV dominant serotype in Guangxi, was expressed in prokaryote. BALB/c mice were immunized with the purified protein. After the serum titer of the immunized mice reached 104 or more, the splenocytes were fused with SP2/0 myeloma cells. After screening by indirect ELISA, monoclonal antibody was prepared by ascites-induced method. Western blotting, IFA and indirect ELISA were used to identify the titer, subtype, reaction specificity and cross-reaction spectrum. And the prepared monoclonal antibody was used for immunohistochemical detection. And the prepared monoclonal antibody was used to detect the IBV in the trachea and kidney tissues of SPF chickens artificially infected with 4 representative IBV variants (GX-N130048, GX-N160421, GX-QZ171023 and GX-QZ170728). [Result] The prepared monoclonal antibody N2D5 had a titer greater than 217 and its subtype was IgG2b. The Western blotting and IFA results showed that the monoclonal antibody N2D5 only reacted with IBV, and were negative with Newcastle disease virus (NDV), infectious laryngotracheitis virus (ILTV), avian metapneumovirus (aMPV), infectious bursal disease virus (IBDV), avian leukosis virus (ALV) and Marek's disease virus (MDV). Monoclonal antibody N2D5 reacted with many genotypes in China and all 7 serotypes of IBV currently prevalent in Guangxi, including commonly used standard strains, vaccine strains and field strains. Immunohistochemistry showed that the virus signals could be detected in the trachea and kidney tissues of SPF chickens at different time after artificial infection of 3 representative IBV strains from chicken and 1 isolated strain from duck, which further proved its broad spectrum. [Conclusion] The monoclonal antibody N2D5 of IBV prepared based on hybridoma technology belongs to the IgG2b subtype. It has the characteristics of high specificity, wide response spectrum and strong binding ability with IBV. It can be used as a specific diagnostic antibody for clinical diagnosis of IBV and the study of virus distribution.

Maternal antibiotic administration during gestation can affect the memory and brain structure in mouse offspring.

Maternal antibiotics administration (MAA) is among the widely used therapeutic approaches in pregnancy. Although published evidence demonstrates that infants exposed to antibiotics immediately after birth have altered recognition memory responses at one month of age, very little is known about in utero effects of antibiotics on the neuronal function and behavior of children after birth. Therefore, this study aimed to evaluate the impact of MAA at different periods of pregnancy on memory decline and brain structural alterations in young mouse offspring after their first month of life. To study the effects of MAA on 4-week-old offspring, pregnant C57BL/6J mouse dams (2-3-month-old; n = 4/group) were exposed to a cocktail of amoxicillin (205 mg/kg/day) and azithromycin (51 mg/kg/day) in sterile drinking water (daily/1 week) during either the 2nd or 3rd week of pregnancy and stopped after delivery. A control group of pregnant dams was exposed to sterile drinking water alone during all three weeks of pregnancy. Then, the 4-week-old offspring mice were first evaluated for behavioral changes. Using the Morris water maze assay, we revealed that exposure of pregnant mice to antibiotics at the 2nd and 3rd weeks of pregnancy significantly altered spatial reference memory and learning skills in their offspring compared to those delivered from the control group of dams. In contrast, no significant difference in long-term associative memory was detected between offspring groups using the novel object recognition test. Then, we histologically evaluated brain samples from the same offspring individuals using conventional immunofluorescence and electron microscopy assays. To our knowledge, we observed a reduction in the density of the hippocampal CA1 pyramidal neurons and hypomyelination in the corpus callosum in groups of mice in utero exposed to antibiotics at the 2nd and 3rd weeks of gestation. In addition, offspring exposed to antibiotics at the 2nd or 3rd week of gestation demonstrated a decreased astrocyte cell surface area and astrocyte territories or depletion of neurogenesis in the dentate gyrus and hippocampal synaptic loss, respectively. Altogether, this study shows that MAA at different times of pregnancy can pathologically alter cognitive behavior and brain development in offspring at an early age after weaning.

The added value of One Health surveillance: data from questing ticks can provide an early signal for anaplasmosis outbreaks in animals and humans.

OBJECTIVE: In 2021, a first outbreak of anaplasmosis occurred in animals and humans in southern Québec, with 64% of confirmed human cases located in Bromont municipality. Ixodes scapularis ticks and Peromyscus mouse ear biopsies collected in Bromont from 2019 to 2021 were analyzed for Anaplasma phagocytophilum (Ap) with the objective of determining whether an early environmental signal could have been detected before the outbreak. METHODS: Samples were collected for a concurrent study aiming to reduce Lyme disease risk. Between 2019 and 2021, up to 14 experimental sites were sampled for ticks and capture of small mammals took place on three sites in 2021. Samples were screened for Ap using multiplex real-time PCR, and genetic strains were identified using a single-nucleotide polymorphism assay. RESULTS: Analyses showed an increase of 5.7% in Ap prevalence in ticks (CI95: 1.5-9.9) between 2019 and 2020, i.e., one year before the outbreak. A majority of Ap-positive ticks were infected with the zoonotic strain (68.8%; CI95: 50.0-83.9) during the study period. In 2021, 2 of 59 captured Peromycus mice were positive for Ap, for a prevalence of 3.4% (CI95: 0.4-11.7). CONCLUSION: We conclude that data collected in Bromont could have provided an early signal for an anaplasmosis risk increasing in the targeted region. This is a reminder that integrated surveillance of tick-borne diseases through structured One Health programs, i.e. systematically integrating data from humans, animals and the environment, can provide useful and timely information for better preparedness and response in public health.

RéSUMé: OBJECTIF: En 2021, suivant une éclosion d'anaplasmoses chez les animaux et les humains dans le sud du Québec, des tiques de l'espèce Ixodes scapularis et des biopsies de souris Peromyscus spp. échantillonées à Bromont, la municipalité où 64 % des cas humains confirmés était localisé, ont été testées pour Anaplasma phagocytophilum (Ap) avec pour objectif de déterminer si un signal environnemental précoce d'augmentation du risque aurait pu être détecté avant l'éclosion. MéTHODE: L'échantillonnage a été réalisé dans le cadre d'une étude visant à réduire le risque de maladie de Lyme. De 2019 à 2021, 14 sites expérimentaux ont été échantillonnés pour les tiques. En 2021, trois sites ont été sélectionnés pour la capture des micromammifères. Les échantillons ont été testés pour la présence d'Ap à l'aide d'un PCR multiplex en temps réelle et les lignées génétiques ont été identifiées grâce à un test de polymorphisme mononucléotidique. RéSULTATS: Les analyses ont montré une augmentation de 5,7 % (IC95% : 1,5­9,9) de la prévalence de Ap entre 2019 et 2020, c'est-à-dire un an avant l'éclosion. Cette augmentation est associée à la présence d'une majorité d'Ap de la lignée zoonotique (68,8 %; IC95% : 50,0­83,9) sur l'ensemble de la période étudiée. En 2021, deux Peromycus spp. capturées sur 59 étaient positives pour Ap pour une prévalence de 3,4 % (IC95% : 0,4­11,7). CONCLUSION: Les données environnementales échantillonnées à Bromont auraient pu fournir un signal précoce de l'augmentation du risque d'anaplasmose dans la région. C'est un rappel que la surveillance intégrée des maladies transmises par les tiques inspirée de l'approche Une seule santé, intégrant systématiquement des données humaines, animales et environnementales, peut fournir des informations utiles et opportunes aux autorités de santé publique.

Mouse models of lung-specific SARS-CoV-2 infection with moderate pathological traits.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) has been a global health concern since 2019. The viral spike protein infects the host by binding to angiotensin-converting enzyme 2 (ACE2) expressed on the cell surface, which is then processed by type II transmembrane serine protease. However, ACE2 does not react to SARS-CoV-2 in inbred wild-type mice, which poses a challenge for preclinical research with animal models, necessitating a human ACE2 (hACE2)-expressing transgenic mouse model. Cytokeratin 18 (K18) promoter-derived hACE2 transgenic mice [B6.Cg-Tg(K18-ACE2)2Prlmn/J] are widely used for research on SARS-CoV-1, MERS-CoV, and SARS-CoV-2. However, SARS-CoV-2 infection is lethal at ≥105 PFU and SARS-CoV-2 target cells are limited to type-1 alveolar pneumocytes in K18-hACE2 mice, making this model incompatible with infections in the human lung. Hence, we developed lung-specific SARS-CoV-2 infection mouse models with surfactant protein B (SFTPB) and secretoglobin family 1a member 1 (Scgb1a1) promoters. After inoculation of 105 PFU of SARS-CoV-2 to the K18-hACE2, SFTPB-hACE2, and SCGB1A1-hACE2 models, the peak viral titer was detected at 2 days post-infection and then gradually decreased. In K18-hACE2 mice, the body temperature decreased by approximately 10°C, body weight decreased by over 20%, and the survival rate was reduced. However, SFTPB-hACE2 and SCGB1A1-hACE2 mice showed minimal clinical signs after infection. The virus targeted type I pneumocytes in K18-hACE2 mice; type II pneumocytes in SFTPB-hACE2 mice; and club, goblet, and ciliated cells in SCGB1A1-hACE2 mice. A time-dependent increase in severe lung lesions was detected in K18-hACE2 mice, whereas mild lesions developed in SFTPB-hACE2 and SCGB1A1-hACE2 mice. Spleen, small intestine, and brain lesions developed in K18-hACE2 mice but not in SFTPB-hACE2 and SCGB1A1-hACE2 mice. These newly developed SFTPB-hACE2 and SCGB1A1-hACE2 mice should prove useful to expand research on hACE2-mediated respiratory viruses.

Transgenic animal models for the functional analysis of ACE2

Angiotensin-converting enzyme 2 (ACE2) is a carboxypeptidase involved in the metabolism of biologically active peptides. Its most important physiological function is the conversion of angiotensin II to angiotensin-(1–7), which initiates the protective arm of the renin–angiotensin system (RAS). To evaluate the physiological relevance of this revision of the RAS, numerous different animal models have been engineered with genetic alterations in ACE2 expression. The characterization of ACE-deficient mice led to the discovery of a second function of the protein being responsible for the trafficking of the neutral amino acid transporter B(0)AT1 to the plasma membrane of gut epithelial cells, thereby promoting the intestinal uptake of certain amino acids. These two different functions are mediated by two domains of ACE2 with homologies to ACE and to collectrin, respectively, which have been fused during evolution. Moreover, some coronaviruses, such as SARS-CoV and SARS-CoV-2, hijack ACE2 for their entry into host cells, and again genetically altered mouse models expressing human ACE2 became instrumental to study virus infection and to develop therapeutic strategies. This chapter will summarize the different transgenic and knockout mouse and rat models with altered expression of ACE2 and the insights they have provided for the functions of this versatile protein. © 2023 Elsevier Inc. All rights reserved.

Lung Inflammation Induced by Inactivated SARS-CoV-2 in C57BL/6 Female Mice Is Controlled by Intranasal Instillation of Vitamin D.

The COVID-19 pandemic was triggered by the coronavirus SARS-CoV-2, whose peak occurred in the years 2020 and 2021. The main target of this virus is the lung, and the infection is associated with an accentuated inflammatory process involving mainly the innate arm of the immune system. Here, we described the induction of a pulmonary inflammatory process triggered by the intranasal (IN) instillation of UV-inactivated SARS-CoV-2 in C57BL/6 female mice, and then the evaluation of the ability of vitamin D (VitD) to control this process. The assays used to estimate the severity of lung involvement included the total and differential number of cells in the bronchoalveolar lavage fluid (BALF), histopathological analysis, quantification of T cell subsets, and inflammatory mediators by RT-PCR, cytokine quantification in lung homogenates, and flow cytometric analysis of cells recovered from lung parenchyma. The IN instillation of inactivated SARS-CoV-2 triggered a pulmonary inflammatory process, consisting of various cell types and mediators, resembling the typical inflammation found in transgenic mice infected with SARS-CoV-2. This inflammatory process was significantly decreased by the IN delivery of VitD, but not by its IP administration, suggesting that this hormone could have a therapeutic potential in COVID-19 if locally applied. To our knowledge, the local delivery of VitD to downmodulate lung inflammation in COVID-19 is an original proposition.

Aggravated pneumonia and diabetes in SARS-CoV-2 infected diabetic mice.

Multiple clinical and epidemiological studies have shown an interconnection between coronavirus disease 2019 (COVID-19) and diabetes, but experimental evidence is still lacking. Understanding the interplay between them is important because of the global health burden of COVID-19 and diabetes. We found that C57BL/6J mice were susceptible to the alpha strain of SARS-CoV-2. Moreover, diabetic C57BL/6J mice with leptin receptor gene deficiency (db/db mice) showed a higher viral load in the throat and lung and slower virus clearance in the throat after infection than C57BL/6J mice. Histological and multifactor analysis revealed more advanced pulmonary injury and serum inflammation in SARS-CoV-2 infected diabetic mice. Moreover, SARS-CoV-2 infected diabetic mice exhibited more severe insulin resistance and islet cell loss than uninfected diabetic mice. By RNA sequencing analysis, we found that diabetes may reduce the collagen level, suppress the immune response and aggravate inflammation in the lung after infection, which may account for the greater susceptibility of diabetic mice and their more severe lung damage after infection. In summary, we successfully established a SARS-CoV-2 infected diabetic mice model and demonstrated that diabetes and COVID-19 were risk factors for one another.

Natural killer (NK) cells: an innate defense shield against respiratory viral infections

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.

Reduced social behavior and heightened anxiety as indicators of depression in SERT knockout mice

Major depressive disorder (MDD) is the most commonly diagnosed psychiatric disorder with a 12-month prevalence rate of 6.7% (Waraich et al., 2004). Now, MDD is one of the leading causes to the global health-related burden, and its prevalence was exacerbated even more by the ramifications of the COVID-19 pandemic and its impact on individuals' mobility and health across most cultures. The link between depression and serotonin suggests that reduced 5-HT signaling is a potential risk factor in the etiology of MDD (Ruhe et al., 2007). One of the classic neurotransmitters in the central nervous system, 5-HT plays an important role in the neural transduction that involves, for example, mood and cognition. Thus, it has been the pharmacological target for effective MDD medications. Young et al. (2014) found when 5-HT levels increase, socially desirable behaviors tend to increase as well. The serotonergic system in the brain involves 5HT and SERT. Previous studies have shown a reduced role capacity of SERT impacts one's vulnerability to anxiety and depression. In this protocol, social motivation was measured in mice through a pair of open and operant conditioning paradigms. Comparisons were made between 13 SERT+/+, 16 SERT+/-, and 8 SERT-/- mice siblings from Any-maze tracking data. Results support the conclusion that SERT-/- mice displayed reduced social functioning and showed more depressive-like symptoms and social memory deficits compared to their SERT+/+ and SERT +/- siblings. This suggests the observed differences in social behavior between SERT+/+, SERT+/-, and SERT-/- mice are directly associated with changes in the SERT gene expression. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

Truncated expression of S1 protein of Feline infectious peritonitis virus and preparation of its monoclonal antibody

In order to develop monoclonal antibody against Feline infectious peritonitis virus (FIPV) S1 protein, the truncated S1 protein (rS1) was expressed through Escherichia coli and subsequently purified. Then BALB/c mice were immunized with purified rSl. Three hybridoma cell strains, named 2D7,3D8 and 5G1, stably secreting antibodies against rSl were obtained by cell fusion and indirect ELISA screening. The identification of antibody subtype showed that antibody subtypes of 2D7,5G1 and 3d8 strains were IgG2a,IgG2a and IgGl,respectively. And the light chain of those three hybridoma cell strains was Kappa. Result of karyotype identification of hybridoma cells showed that the chromosome numbers of those three hybridoma cells were about 102,101 and 103, which was belonged to the karyotype of hybridoma. The titer of ascites antibody for indirect ELISA was 1 : 204 800, and monoclonal antibodies were purified. Moreover, all of 2D7,3D8 and 5G1 could react with rS1 by Western-blot and FIPV in cells by IFA. These data suggest that three monoclonal antibodies against rSl with good activities were ideal materials in the study of early diagnosis of FIPV and the biological function of FIPV in the future.

Evaluation of antiviral effects and toxicity of herbal medicine Vipdervir capsules

Background: Antiviral vaccine is not effective, synthetic antiviral drugs are highly toxic, leading to increased interest in herbal medicines as promising antiviral drugs. Recently, Vipdervir has been developed from medicinal herbs with the aim to support and treat diseases caused by viruses such as H5N1 and SARSCoV- 2. In the present study, we assessed Vipdervir's antiviral activity against H5N1 and SARS-CoV-2. In addition, we also evaluated the acute toxicity and repeated dose toxicity of Vipdervir in mice and rabbits, respectively. Methods: H5N1 inhibitory effect of Vipdervir was assessed using hemagglutination inhibition assay. Vipdervir's SARS-CoV-2 inhibitory effect was evaluated by Plaque Reduction Neutralization assay. Acute and repeated dose oral toxicities of Vipdervir were determined according to OECD 423 and OECD 407 guidelines, respectively. Results: Data show that Vipdervir is effective against both H5N1 and SARSCoV- 2. At concentrations of 3 mg/mL and 5 mg/mL Vipdervir completely inhibits H5N1. At a concentration of 50 g/mL Vipdervir showed an inhibitory effect on SARS-CoV-2. Acute toxicity data revealed that the LD50 of Vipdervir is greater than 35200 mg/kg, b.wt. in mice. Repeated toxicity data indicated that Vipdervir did not induce significant differences in body weight gain, hematology and clinical biochemistry in compared to the control group. The No Observed Adverse Effect Level of Vipdervir is greater than 613.8 mg/kg b.wt./day in rabbits. No delayed toxicity effects of Vipdervir were observed. Conclusion: Vipdervir capsules were found to be antiviral effective and relatively safe in the tested doses and experimental conditions.