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Background & Aim: With larger accessibility and increased number of patients being treated with CART cell therapy, real-world toxicity continues to remain a significant challenge to its widespread adoption. We have previously shown that allogeneic umbilical cord blood derived (UCB) regulatory T cells (Tregs) can resolve uncontrolled inflammation and can treat acute and immune mediated lung injury in a xenogenic model as well as in patients suffering from COVID-19 acute respiratory distress syndrome. The unique properties of UCB Tregs including: i) lack of plasticity when exposed to inflammatory micro-environments;ii) no requirement for HLA matching;iii) long shelf life of cryopreserved Tregs;and iv) immediate product availability for on demand treatment, makes them an attractive source for treating acute inflammatory syndromes. Therefore, we hypothesized that add-on therapy with UCB derived Tregs may resolve uncontrolled inflammation responsible for CART cell therapy associated toxicity. Methods, Results & Conclusion(s): UCB Tregs were added in 1:1 ratio to CART cells, where no interference in their ability to kill CD19+ Raji cells, was detected at different ratios : 8:1 (80.4% vs. 81.5%);4:1 (62.0% vs. 66.2%);2:1 (50.1% vs. 54.7%);1:1 (35.4% vs. 44.1%) (Fig 1A). In a xenogenic B cell lymphoma model, multiple injections of Tregs were administered after CART injection (Fig 1B), which did not impact distribution of CD8+ T effector cells (Fig 1C) or CART cells cells (Fig 1D) in different organs. No decline in the CAR T levels was observed in the Tregs recipients (Fig 1E). Specifically, no difference in tumor burden was detected between the two arms (Fig 2A). No tumor was detected in CART+Tregs in liver (Fig 2B) or bone marrow (Fig 2C). A corresponding decrease in multiple inflammatory cytokines in peripheral blood was observed in CART+Tregs when compared to CART alone (Fig 2D). Here we show "proof of concept" for add-on therapy with Tregs to mitigate hyper-inflammatory state induced by CART cells without interference in their on-target anti-tumor activity. The timing of Tregs administration after CART cells have had sufficient time for forming synapse with tumor cells allows for preservation of their anti-tumor cytotoxicity, such that the infused Tregs home to the areas of tissue damage to bind to the resident antigen presenting cells which in turn collaborate with Tregs to resolve inflammation. Such differential distribution of cells allow for a Treg "cooling blanket" and lays ground for clinical study. [Figure presented]Copyright © 2023 International Society for Cell & Gene Therapy
ABSTRACT
Covid-19 virus variants identified so far are due to viral genetic diversity, genetic evolution, and variable infectivity, suggesting that high infection rates and high mortality rates may be contributed by these mutations. And it has been reported that the targeting strategies for innate immunity should be less vulnerable to viral evolution, variant emergence and resistance. Therefore, the most effective solution to Covid-19 infection has been proposed to prevent and treat severe exacerbation of patients with moderate disease by enhancing human immune responses such as NK cell and T cell. In previous studies, we demonstrated for the first time that gamma-PGA induced significant antitumor activity and antiviral activity by modulating NK cell-mediated cytotoxicity. Especially intranasal administration of gamma-PGA was found to effectively induce protective innate and CTL immune responses against viruses and we found out that gamma-PGA can be an effective treatment for cervical intraepithelial neoplasia 1 through phase 2b clinical trial. In this study, the possibility of gamma-PGA as a Covid-19 immune modulating agent was confirmed by animal experiments infected with Covid-19 viruses. After oral administration of gamma-PGA 300mug/mouse once a day for 5 days in a K18-hACE2 TG mouse model infected with SARS-CoV-2 (NCCP 43326;original strain) and SARS-CoV-2 (NCCP 43390;Delta variant), virus titer and clinical symptom improvement were confirmed. In the RjHan:AURA Syrian hamster model infected with SARS-CoV-2 (NCCP 49930;Delta variant), 350 or 550 mug/head of gamma-PGA was administered orally for 10 days once a day. The virus for infection was administered at 5 x 104 TCID50, and the titer of virus and the improvement of pneumonia lesions were measured to confirm the effectiveness in terms of prevention or treatment. In the mouse model infected with original Covid-19 virus stain, the weight loss was significantly reduced and the survival rate was also improved by the administration of gamma-PGA. And gamma-PGA alleviated the pneumonic lesions and reduced the virus titer of lung tissue in mice infected with delta variant. In the deltavariant virus infected hamster model, gamma-PGA showed statistically significant improvement of weight loss and lung inflammation during administration after infection. This is a promising result for possibility of Covid-19 therapeutics along with the efficacy results of mouse model, suggesting gammaPGA can be therapeutic candidate to modulate an innate immune response for Covid-19.
ABSTRACT
mRNA is a new class of drugs that has the potential to revolutionize the treatment of brain tumors. Thanks to the COVID-19 mRNA vaccines and numerous therapy-based clinical trials, it is now clear that lipid nanoparticles (LNPs) are a clinically viable means to deliver RNA therapeutics. However, LNP-mediated mRNA delivery to brain tumors remains elusive. Over the past decade, numerous studies have shown that tumor cells communicate with each other via small extracellular vesicles, which are around 100 nm in diameter and consist of lipid bilayer membrane similar to synthetic lipidbased nanocarriers. We hypothesized that rationally designed LNPs based on extracellular vesicle mimicry would enable efficient delivery of RNA therapeutics to brain tumors without undue toxicity. We synthesized LNPs using four components similar to the formulation used in the mRNA COVID19 vaccines (Moderna and Pfizer): ionizable lipid, cholesterol, helper lipid and polyethylene glycol (PEG)-lipid. For the in vitro screen, we tested ten classes of helper lipids based on their abundance in extracellular vesicle membranes, commercial availability, and large-scale production feasibility while keeping rest of the LNP components unchanged. The transfection kinetics of GFP mRNA encapsulated in LNPs and doped with 16 mol% of helper lipids was tested using GL261, U87 and SIM-A9 cell lines. Several LNP formations resulted in stable transfection (upto 5 days) of GFP mRNA in all the cell lines tested in vitro. The successful LNP candidates (enabling >80% transfection efficacy) were then tested in vivo to deliver luciferase mRNA to brain tumors via intrathecal administration in a syngeneic glioblastoma (GBM) mouse model, which confirmed luciferase expression in brain tumors in the cortex. LNPs were then tested to deliver Cre recombinase mRNA in syngeneic GBM mouse model genetically modified to express tdTomato under LoxP marker cassette that enabled identification of LNP targeted cells. mRNA was successfully delivered to tumor cells (70-80% transfected) and a range of different cells in the tumor microenvironment, including tumor-associated macrophages (80-90% transfected), neurons (31- 40% transfected), neural stem cells (39-62% transfected), oligodendrocytes (70-80% transfected) and astrocytes (44-76% transfected). Then, LNP formulations were assessed for delivering Cas9 mRNA and CD81 sgRNA (model protein) in murine syngeneic GBM model to enable gene editing in brain tumor cells. Sanger sequencing showed that CRISPR-Cas9 editing was successful in ~94% of brain tumor cells in vivo. In conclusion, we have developed a library of safe LNPs that can transfect GBM cells in vivo with high efficacy. This technology can potentially be used to develop novel mRNA therapies for GBM by delivering single or multiple mRNAs and holds great potential as a tool to study brain tumor biology.
ABSTRACT
Many zoonotic diseases are found in wild animals and present a serious risk to human health, in particularly the virus carried by birds flying freely around the world is hard to control. There are three main bird migration routes which cover the most areas of China. It is important to investigate and fully understand the types of avian transmitted diseases in key areas on the bird migration routines and its impacts on both birds and human health. However, no literature is available in how about the risk of virus carried by migrating birds, and how to predict and reduce this risk of virus spreading to human being so far. In this paper, we first reviewed the main pathogen types carried by birds, including coronaviruses, influenza viruses, parasites, Newcastle disease virus (NDV), etc., and then discussed the spread risk of avian viruses to human being and animals in key areas of biosafety prevention. We also analyzed and discussed the risk of cross-spread of diseases among different bird species in nature reserves located on bird migration routes which provide sufficient food sources for migratory birds and attract numerous birds. Diseases transmitted by wild birds pose a serious threat to poultry farms, where high density of poultry may become avian influenza virus (AIV) reservoirs, cause a risk of avian influenza outbreaks. Airports are mostly built in suburban areas or remote areas with good ecological environment. There are important transit places for bird migration and densely populated areas, which have serious risk of disease transmission. Finally, this paper puts forward the following prevention suggestions from three aspects. First, establish and improve the monitoring and prediction mechanism of migratory birds, and use laser technology to prevent contact between wild birds and poultry. Second, examine and identify virus types carried by birds in their habitats and carry out vaccination. Third, protect the ecological environment of bird habitat, and keep wild birds in their natural habitat, so as to reduce the contact between wild birds and human and poultry, and thus reduce the risk of virus transmission.
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We examine the relationship of home food procurement (HFP) during COVID-19 to emotional eating and stress using a statewide representative survey (n = 600) in Vermont. Women and people with a job change since COVID-19 were more likely to experience higher stress and emotional eating. Engaging in HFP, especially gardening, is associated with less emotional eating. However, people who fished, hunted, or canned more since the pandemic began were more likely to eat for emotional reasons and experience higher stress. These results suggest that gardening, even during a pandemic, may contribute to stress reduction, more so than other nature-based food production activities.Copyright © 2022 Taylor & Francis Group, LLC.
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Delivery of self-amplifying mRNA (SAM) has high potential for infectious disease vaccination due to its self-adjuvanting and dose-sparing properties. Yet a challenge is the susceptibility of SAM to degradation and the need for SAM to reach the cytosol fully intact to enable self-amplification. Lipid nanoparticles are successfully deployed at incredible speed for mRNA vaccination, but aspects such as cold storage, manufacturing, efficiency of delivery, and the therapeutic window can benefit from further improvement. To investigate alternatives to lipid nanoparticles, a class of >200 biodegradable end-capped lipophilic poly(beta-amino ester)s (PBAEs) that enable efficient delivery of SAM in vitro and in vivo as assessed by measuring expression of SAM encoding reporter proteins is developed. The ability of these polymers to deliver SAM intramuscularly in mice is evaluated, and a polymer-based formulation that yields up to 37-fold higher intramuscular (IM) expression of SAM compared to injected naked SAM is identified. Using the same nanoparticle formulation to deliver a SAM encoding rabies virus glycoprotein, the vaccine elicits superior immunogenicity compared to naked SAM delivery, leading to seroconversion in mice at low RNA injection doses. These biodegradable nanomaterials may be useful in the development of next-generation RNA vaccines for infectious diseases.Copyright © 2023 The Authors. Advanced Therapeutics published by Wiley-VCH GmbH.
ABSTRACT
Dayuanyin (DYY) has been shown to reduce lung inflammation in both coronavirus disease 2019 (COVID-19) and lung injury. This experiment was designed to investigate the efficacy and mechanism of action of DYY against hypoxic pulmonary hypertension (HPH) and to evaluate the effect of DYY on the protection of lung function. Animal welfare and experimental procedures are approved and in accordance with the provision of the Animal Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Science. Male C57/BL6J mice were randomly divided into 4 groups: control group, model group, DYY group (800 mg.kg-1), and positive control sildenafil group (100 mg.kg-1). The animals were given control solvents or drugs by gavage three days in advance. On day 4, the animals in the model group, DYY group and sildenafil group were kept in a hypoxic chamber containing 10% +/- 0.5% oxygen, and the animals in the control group were kept in a normal environment, and the control solvent or drugs continued to be given continuously for 14 days. The right ventricular systolic pressure, right ventricular hypertrophy index, organ indices and other metrics were measured in the experimental endpoints. Meantime, the expression levels of the inflammatory factors in mice lung tissues were measured. The potential therapeutic targets of DYY on pulmonary hypertension were predicted using network pharmacology, the expression of nuclear factor kappa B (NF- kappaB) signaling pathway-related proteins were measured by Western blot assay. It was found that DYY significantly reduced the right ventricular systolic pressure, attenuated lung injury and decreased the expression of inflammatory factors in mice. It can also inhibit hypoxia-induced activation of NF- kappaB signaling pathway. DYY has a protective effect on lung function, as demonstrated by DYY has good efficacy in HPH, and preventive administration can slow down the disease progression, and its mechanism may be related to inhibit the activation of NF-kappaB and signal transducer and activator of transcription 3 (STAT3) by DYY.Copyright © 2023, Chinese Pharmaceutical Association. All rights reserved.
ABSTRACT
The aim of this study was to measure the effect of equine assisted services (EAS) on mood and anxiety in health-care workers. While the emotional toll of the COVID-19 pandemic has been felt in every aspect of our society, health-care workers have been hit especially hard. A survey conducted by Mental Health America during June - September in 2020, found 93% of health-care workers were experiencing stress and 86% reported experiencing anxiety. There is research to support a wide range of interventions to address stress, low mood, and anxiety, including pharmaceuticals, physical exercise, and animal interaction. While several studies have shown an improvement in anxiety and mood after interaction with horses, few studies have included a physically active control group to consider the effect of exercise on results. In this study conducted in October 2021, participants were recruited from area hospitals and randomly assigned to a control group (30-min guided walk with no horse interaction, n = 17), a low level EAS group (30-min self-guided farm tour, n = 20), or a mid-level EAS group (30 min of grooming a horse, n = 19). Before the intervention, participants completed a demographic survey. Pre and post activity, participants completed the Brief Mood Introspection Scale (BMIS) and State Anxiety Inventory for AdultsTM that measured currentfeelings of mood and anxiety, respectively. Data were analyzed using the repeated measures one-way ANOVA procedure in SPSS. This study was approved by the MSU Human Research and Protection Program and the Institutional Animal Care and Use Committee. Fifty-six health-care workers participated in the study, with 32% having worked in health care for less than 5 years and 33.9% having worked in health care for over 20 years. All participants had a significant improvement in State-Anxiety scores after completing their group activity (P < 0.001), with no differences among groups. Similarly, all groups had an improved BMIS score (P < 0.001). However, there was significantly greater improvement in BMIS scores in the mid-level EAS (P < 0.01) when compared with the control group. While all participants in this study improved both their current feelings of anxiety and mood after completing an activity on the farm, there was a greater improvement in mood in those individuals who spent 30 min grooming a horse when compared with the walk group without horse interaction. The results from this study provide further support for the impact of equine assisted services as a means of improving mood.Copyright © 2023
ABSTRACT
Objective: In the twenty-first century, despite the development in infection management, and improvement of vaccines and therapeutic agents in the field of health, new viral outbreaks that can still be fatal in humans and animals are emerging. The infection of zoonosis COVID-19 from bat origin, the intermediate host of which is still being unclear, has appeared in people who visited animal bazaar in December 2019, in Wuhan, China. The World Health Organization declared this infection a pandemic in February 2020. Millions of people have been affected by this pandemic. The fight against the pandemic has had a great economic cost and continues to do so. Even people have changed their lifestyle. In this context, there have been concerns about companion animals with COVID-19 transmission, from human to animal or animal to human. The purpose of this review was to examine the studies on the presence and transmission of COVID-19 in companion animals such as cats, dogs, hamsters and horses. Result and Discussion: It has been reported in studies that most of the companion animals (cat, dog and hamster) were susceptible to SARS-CoV-2, and humans could be a source of infection for them. However, the potential role of companion animals in transmission to humans is not fully known. It is clear from this pandemic that the necessity of epidemiological investigation of infectious agents, especially zoonotic ones, in one health concept has emerged once again.Copyright © 2022 University of Ankara. All rights reserved.
ABSTRACT
Broiler chicken eggs are one of the main and strategic foods for the people of Indonesia and contribute to regional and national inflation. Broiler egg production in Indonesia differs between regions. Areas with a surplus of eggs tend to have lower prices than areas with a deficit. This research is to measure the transmission of broiler egg prices between markets in surplus and deficit areas, using weekly price time series data for the period January 2018-December 2021. Areas of surplus broiler eggs, East Java Province (the highest broiler egg production in Indonesia) which become one of the main suppliers to the Province of East Nusa Tenggara as a deficit area. Using the Johannsen cointegration test it is found that there is no cointegration or there is no relationship between the surplus and deficit regions in the long term but not in the short term. Factors of marketing infrastructure, market information systems, and geographical conditions can be obstacles to the absence of cointegration. The VAR (Vector Auto-Regressive) Vector Error Correction model (VECM) test, found that price transmission occurred between surplus and deficit areas, meaning that between the two regions, there was market integration prior to Covid. The transmission has weakened, and due to the Covid situation, there have been restrictions on the movement of people and goods. The government and other market players need to study the response of the broiler egg market, in the short and long term so that market players can make the right policies.
ABSTRACT
Ionizable amino lipids are a major constituent of the lipid nanoparticles for delivering nucleic acid therapeutics (e.g., DLin-MC3-DMA in ONPATTRO , ALC-0315 in Comirnaty , SM-102 in Spikevax ). Scarcity of lipids that are suitable for cell therapy, vaccination, and gene therapies continue to be a problem in advancing many potential diagnostic/therapeutic/vaccine candidates to the clinic. Herein, we describe the development of novel ionizable lipids to be used as functional excipients for designing vehicles for nucleic acid therapeutics/vaccines in vivo or ex vivo use in cell therapy applications. We first studied the transfection efficiency (TE) of LNP-based mRNA formulations of these ionizable lipid candidates in primary human T cells and established a workflow for engineering of primary immune T cells. We then adapted this workflow towards bioengineering of CAR constructs to T cells towards non-viral CAR T therapy. Lipids were also tested in rodents for vaccine applications using self-amplifying RNA (saRNA) encoding various antigens. We have then evaluated various ionizable lipid candidates and their biodistribution along with the mRNA/DNA translation exploration using various LNP compositions. Further, using ionizable lipids from the library, we have shown gene editing of various targets in rodents. We believe that these studies will pave the path to the advancement in nucleic acid based therapeutics and vaccines, or cell gene therapy agents for early diagnosis and detection of cancer, and for targeted genomic medicines towards cancer treatment and diagnosis.
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PurposeThis research conceptualises the hallmark event, Melbourne Cup in Australia, as a major sporting brand experience. While numerous studies have explored consumer engagement and experiences in major sporting events, few research studies highlight the negative issues, such as alcoholism, gambling and violence, that may affect consumer engagement and experience. This article addresses the challenges and opportunities of providing immersive and transformative experiences through transformative service research (TSR) approaches when such negative issues are swirling around.Design/methodology/approachThe paper is conceptual. It uses the example of Melbourne Cup to illuminate aspects of the conceptual framework.FindingsThe article unpacks a myriad of positive and negative immersive brand experiences and contributes a conceptual framework to understand the sporting brand experience phenomenon and shows how authentically responsible marketing approaches can improve the sport spectator experience.Research limitations/implicationsInsights from the extended TSR framework presents implications for various organisations that are involved with strategic destination marketing approaches. It guides key stakeholders to engage in dialogue and collaborate in order to improve the attendee transformative experience. Inviting collaborators will facilitate the exchange of ideas that will improve event organisation. Consistent approaches among hospitality service providers would improve alcohol service and create a safe environment for attendees. The TSR framework guides players of the experience to engage in meaningful dialogue with a common goal to improve consumer wellbeing. Education and training therefore are key elements in the consumer sporting brand experience.Practical implicationsThe adapted TSR framework offers insights to destination marketers such as sporting agencies, tour operators and sporting organisations/clubs. Marketers may promote bigger sporting events and organise tours via travel agencies and ignore key elements that may influence attendee decision. Destination marketing organisations (DMOs) can use the framework to promote effective planning and the key initiatives that the iconic event is involved with. The framework can be used as a guide to manage similar international events. Events of major or mega size and international reputation need specific frameworks that address crowd behaviours of similar sizes.Originality/valueAn extended transformative service approach is being conceptualised for major sporting brand experiences. Practical implications are also highlighted for DMOs when raising the profile of city brands.
ABSTRACT
Glioblastoma is an extremely aggressive and difficult cancer to treat, which may partly be due to its limited ability to induce T-cell responses. However, combining viral vector vaccines with other therapies to generate tumor-specific T cells may provide a meaningful benefit to patients. Here, we investigated whether heterologous prime-boost vaccination with chimpanzee-derived adenoviral vector ChAdOx1 and modified vaccinia Ankara (MVA) vaccines could generate therapeutically effective CD8+ T-cell responses against a model antigen P1A, a mouse homolog of human tumorassociated Melanoma Antigen GenE (MAGE)-type antigens, expressed by a BGL-1 mouse glioblastoma cell line. We demonstrated that heterologous prime-boost vaccination with ChAdOx1/MVA vaccines targeting P1A generated a high magnitude of CD8+ T cells specific for the P1A35-43 epitope presented by the MHC class I molecule H-2Ld . Prophylactic vaccination with ChAdOx1/MVA-P1A significantly prolonged the survival of syngeneic mice subcutaneously challenged with P1A-expressing BGL-1 tumors. Furthermore, different vaccination schedules significantly impact the magnitude of antigen-specific CD8+ T-cell responses and may impact protective efficacy. However, the substantial induction of myeloid-derived suppressor cells (MDSCs) by this tumor model presents a significant challenge in the therapeutic setting. Future work will investigate the efficacy of this vaccination strategy on intracranial P1A-expressing BGL-1 models.
ABSTRACT
Lung cancer is the leading cause of cancer related deaths worldwide, with a relatively low 5-year survival rate. Although there are some therapies against lung cancer, new effective treatment options are urgently required. Recently during the COVID-19 pandemic, we have seen that SARSCoV-2 binds to its receptor angiotensin-converting enzyme 2 (ACE2) via spike S1 to enter the cells. This study underlines the importance of SARS-CoV-2 spike S1 in inducing death in human lung cancer cells. Interestingly, we have seen that recombinant spike S1 treatment at very low doses led to death of human A549 lung cancer cells. On the other hand, boiled recombinant SARS-CoV-2 spike S1 remained unable to induce death, suggesting that the induction of cell death in A549 cells was due to native SARS-CoV-2 spike S1 protein. SARS-CoV-2 spike S1-induced A549 cell death was also inhibited by neutralizing antibodies against spike S1 and ACE2. Moreover, our newly designed wild type ACE2-interacting domain of SARS-CoV-2 (wtAIDS), but not mAIDS, peptide also attenuated SARS-CoV-2 spike S1-induced cell death, suggesting that SARS-CoV-2 spike S1- induced death in lung cancer cells depends on its interaction with ACE2 receptor. Similarly, recombinant spike S1 treatment also led to death of H1299 and H358 human lung cancer cells. Finally, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) intoxication led to the formation tumors in lungs of A/J mice and alternate day intranasal treatment with low dose of recombinant SARS-CoV-2 spike S1 from 22-weeks of NNK insult (late stage) led to induced apoptosis and tumor regression in the lungs. These studies indicate that recombinant SARS-CoV-2 Spike S1 protein may have implications in the treatment of lung cancer.
ABSTRACT
Canine parvovirus (CPV), canine coronavirus (CCoV) and canine rotavirus (CRV) are the three main causative viruses of diarrhea in dogs with similar clinical symptoms;thereby it is necessary to establish a high effective molecular detection method for differentiating the above pathogens. By optimizing the primer concentration and annealing temperature, a triple PCR method was established for simultaneous detection of CPV, CCoV and CRV, and then the specificity, sensitivity and repeatability of the method were tested. The results showed that the target fragments of CPV VP2 gene (253 bp), CCoV ORF-1b gene (379 bp) and CRV VP6 gene (852 bp) could be accurately amplified by the triple PCR method with high specificity, the detection limits of CPV, CCOV and CRV were 6.44x10-1 pg/L, 8.72x10-1 pg/L and 8.35x10-1 pg/L respectively with high sensitivity, and the method had good stability. Using this triple PCR method, 135 canine diarrhea fecal samples collected in Chengdu region from 2019 to 2020 were detected, and compared with those of single PCR method. The detection rates of CPV, CCoV and CRV were 16.30%, 20.74% and 4.44%, respectively, and the total infection rate was 51.11% (65/135) with 20.00% (13/65) co-infection rate. The detection results were consistent with three single PCR methods. In conclusion, CPV/CCoV/CRV triple PCR method successfully established in this paper can be applied as an effective molecular method to detection of related pathogens and to the epidemiological investigation.
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The current ethical paradigm condones the use of nonhuman animals for biomedical research experiments. Such use of animals has been acknowledged as a practice that comes with a considerable moral burden, and thus certain regulations have been established to control it. The singularity of nonhuman primates (NHPs), in terms of their cognitive and emotional complexity, grants them virtual personhood status, which is reflected in a stricter legislation, that nonetheless allows their use in certain cases. The pandemic brought about by SARS-CoV-2 has accelerated the classical drug development design model, and NHPs have been among the species used to test novel therapies. In this study, a search on the characteristics of NHPs and experimental techniques performed for COVID-19 vaccine development purposes will be used to weigh the costs and benefits of these practices. Taking a critical viewpoint, the results of these studies will be analyzed beyond their quantitative dimensions, considering the harm entailed for humans and NHPs, as well as the extension of potential benefits. © 2022, BAU College of Arts and Design Barcelona. All rights reserved.
ABSTRACT
Introduction: Lactate is a common biomarker used in multiple surgical subspecialties. No one has previously measured coronary sinus lactate reduction as a result of drug administration. We therefore tested the hypothesis that IV geranylgeranylacetone (GGA), a novel agent used to treat human peptic ulcer disease, would result in reduced coronary sinus lactate production. Method(s): New Zealand adult rabbits (N=5 each) received IV 50 mg/kg GGA 24 hours before intervention, which consisted of Langendorff perfusion, 30 min of global normothermic cardioplegic arrest, followed by reperfusion. Myocardial release of lactate was measured. HSP70 was quantified by western blot. Differences between GGA+ and GGA- groups pre- and post-ischemia were analyzed by unpaired t-tests. Result(s): In the GGA- group, lactate increased immediately at one minute and throughout the duration of reperfusion. However, in GGA+ hearts, lactate also increased at one min of reperfusion but then continued to decrease throughout the remainder of reperfusion. Lactate was significantly less at every time point of reperfusion in GGA+. Integrated lactate area was significantly less throughout reperfusion in GGA+. Conclusion(s): GGA induced caused a marked decrease in coronary sinus lactate release during reperfusion. Simultaneously intravenously GGA induced myocardial HSP70i and reduced myocardial damage. Further study of the effects and mechanisms involved is indicated. Application to other organs is useful as well. Heat shock proteins (HSPS) are also antithrombotic. Given the thrombotic nature of Covid, induction of HSPS may be beneficial in decreasing the cardiac thoracic and vascular complications of Covid and allowing faster resolution of this disease during to vascular complications.
ABSTRACT
Severe acute respiratory syndrome coronavirus (SARS-CoV-2), the causative agent of the current COVID-19 pandemic, has evolved to have a wide range of hosts, including non-human primates, wild and domestic animals. Determining the susceptibility of different animal species to SARS-CoV-2 infection and the role of animals in the epidemiology of the disease will be critical to designing appropriate human and veterinary public health responses to this pandemic. A better understanding of the susceptibility of animal species to SARS-CoV-2 may help clarify transmission mechanisms and identify potential reservoirs and sources of infection that are important for both animal and human health. The current pandemic produced by SARS CoV-2 and its variants represents an example of the unique concept of health (One Health) in which humans and animals are components of the same epidemiological chain. In this paper, only the natural infections found in different animals species will be reviewed, according to literature data, regarding the species of affected animals, the transmission patterns (human-animal, animal-human), clinical aspects, diagnosis confirmation and a brief presentation of the prevention possibilities through vaccination.
ABSTRACT
The United Nations Secretary-General Mechanism (UNSGM) for investigation of the alleged use of chemical and biological weapons is the only established international mechanism of this type under the UN. The UNGSM may launch an international investigation, relying on a roster of expert consultants, qualified experts, and analytical laboratories nominated by the member states. Under the framework of the UNSGM, we organized an external quality assurance exercise for nominated laboratories, named the Disease X Test, to improve the ability to discover and identify new pathogens that may cause possible epidemics and to determine their animal origin. The "what-if" scenario was to identify the etiological agent responsible for an outbreak that has tested negative for many known pathogens, including viruses and bacteria. Three microbes were added to the samples, Dabie bandavirus, Mammarenavirus, and Gemella spp., of which the last two have not been taxonomically named or published. The animal samples were from Rattus norvegicus, Marmota himalayana, New Zealand white rabbit, and the tick Haemaphysalis longicornis. Of the 11 international laboratories that participated in this activity, six accurately identified pathogen X as a new Mammarenavirus, and five correctly identified the animal origin as R. norvegicus. These results showed that many laboratories under the UNSGM have the capacity and ability to identify a new virus during a possible international investigation of a suspected biological event. The technical details are discussed in this report.Copyright © 2022