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Hantaviruses are zoonotically transmitted from rodents to humans through the respiratory route, with no currently approved antivirals or widely available vaccines. The recent discovery of interhuman-transmitted Andes virus (ANDV) necessitates the systematic identification of cell tropism, infective potential, and potent therapeutic agents. We utilized human primary lung endothelial cells, various pluripotent stem cell-derived heart and brain cell types, and established human lung organoid models to evaluate the tropisms of Old World Hantaan (HTNV) and New World ANDV and Sin Nombre (SNV) viruses. ANDV exhibited broad tropism for all cell types assessed. SNV readily infected pulmonary endothelial cells, while HTNV robustly amplified in endothelial cells, cardiomyocytes, and astrocytes. We also provide the first evidence of hantaviral infection in human 3D distal lung organoids, which effectively modeled these differential tropisms. ANDV infection transcriptionally promoted cell injury and inflammatory responses, and downregulated lipid metabolic pathways in lung epithelial cells. Evaluation of selected drug candidates and pharmacotranscriptomics revealed that the host-directed small molecule compound urolithin B inhibited ANDV infection and restored cellular metabolism with minimal changes in host transcription. Given the scarcity of academic BSL-4 facilities that enable in vivo hantaviral studies, this investigation presents advanced human cell-based model systems that closely recapitulate host cell tropism and responses to infection, thereby providing critical platforms to evaluate potential antiviral drug candidates.

Novel therapeutic strategies are needed to attenuate increased systemic and gut inflammation that contribute to morbidity and mortality in chronic HIV infection despite potent antiretroviral therapy (ART). The goal of this study is to use preclinical models of chronic treated HIV to determine whether the antioxidant and anti-inflammatory apoA-I mimetic peptides 6F and 4F attenuate systemic and gut inflammation in chronic HIV. We used two humanized murine models of HIV infection and gut explants from 10 uninfected and 10 HIV infected persons on potent ART, to determine the in vivo and ex vivo impact of apoA-I mimetics on systemic and intestinal inflammation in HIV. When compared to HIV infected humanized mice treated with ART alone, mice on oral apoA-I mimetic peptide 6F with ART had consistently reduced plasma and gut tissue cytokines (TNF-α, IL-6) and chemokines (CX3CL1) that are products of ADAM17 sheddase activity. Oral 6F attenuated gut protein levels of ADAM17 that were increased in HIV-1 infected mice on potent ART compared to uninfected mice. Adding oxidized lipoproteins and endotoxin (LPS) ex vivo to gut explants from HIV infected persons increased levels of ADAM17 in myeloid and intestinal cells, which increased TNF-α and CX3CL1. Both 4F and 6F attenuated these changes. Our preclinical data suggest that apoA-I mimetic peptides provide a novel therapeutic strategy that can target increased protein levels of ADAM17 and its sheddase activity that contribute to intestinal and systemic inflammation in treated HIV. The large repertoire of inflammatory mediators involved in ADAM17 sheddase activity places it as a pivotal orchestrator of several inflammatory pathways associated with morbidity in chronic treated HIV that make it an attractive therapeutic target.

In humans, acute and chronic respiratory infections caused by viruses are associated with considerable morbidity and mortality. Respiratory viruses infect airway epithelial cells and induce oxidative stress, yet the exact pathogenesis remains unclear. Oxidative stress activates the transcription factor NRF2, which plays a key role in alleviating redox-induced cellular injury. The transcriptional activation of NRF2 has been reported to affect both viral replication and associated inflammation pathways. There is complex bidirectional crosstalk between virus replication and the NRF2 pathway because virus replication directly or indirectly regulates NRF2 expression, and NRF2 activation can reversely hamper viral replication and viral spread across cells and tissues. In this review, we discuss the complex role of the NRF2 pathway in the regulation of the pathogenesis of the main respiratory viruses, including coronaviruses, influenza viruses, respiratory syncytial virus (RSV), and rhinoviruses. We also summarize the scientific evidence regarding the effects of the known NRF2 agonists that can be utilized to alter the NRF2 pathway.

Respiratory viruses constitute a significant cause of illness and death worldwide. Respiratory virus-associated injuries include oxidative stress, ferroptosis, inflammation, pyroptosis, apoptosis, fibrosis, autoimmunity, and vascular injury. Several studies have demonstrated the involvement of the nuclear factor erythroid 2-related factor 2 (Nrf2) in the pathophysiology of viral infection and associated complications. It has thus emerged as a pivotal player in cellular defense mechanisms against such damage. Here, we discuss the impact of Nrf2 activation on airway injuries induced by respiratory viruses, including viruses, coronaviruses, rhinoviruses, and respiratory syncytial viruses. The inhibition or deregulation of Nrf2 pathway activation induces airway tissue damage in the presence of viral respiratory infections. In contrast, Nrf2 pathway activation demonstrates protection against tissue and organ injuries. Clinical trials involving Nrf2 agonists are needed to define the effect of Nrf2 therapeutics on airway tissues and organs damaged by viral respiratory infections.

Novel therapeutic strategies are needed to attenuate increased systemic and gut inflammation that contribute to morbidity and mortality in chronic HIV infection despite potent antiretroviral therapy (ART). The goal of this study is to use preclinical models of chronic treated HIV to determine whether the antioxidant and anti-inflammatory apoA-I mimetic peptides 6F and 4F attenuate systemic and gut inflammation in chronic HIV. We used two humanized murine models of HIV infection and gut explants from 10 uninfected and 10 HIV infected persons on potent ART, to determine the in vivo and ex vivo impact of apoA-I mimetics on systemic and intestinal inflammation in HIV. When compared to HIV infected humanized mice treated with ART alone, mice on oral apoA-I mimetic peptide 6F with ART had consistently reduced plasma and gut tissue cytokines (TNF-α, IL-6) and chemokines (CX3CL1) that are products of ADAM17 sheddase activity. Oral 6F attenuated gut protein levels of ADAM17 that were increased in HIV-1 infected mice on potent ART compared to uninfected mice. Adding oxidized lipoproteins and endotoxin (LPS) ex vivo to gut explants from HIV infected persons increased levels of ADAM17 in myeloid and intestinal cells, which increased TNF-α and CX3CL1. Both 4F and 6F attenuated these changes. Our preclinical data suggest that apoA-I mimetic peptides provide a novel therapeutic strategy that can target increased protein levels of ADAM17 and its sheddase activity that contribute to intestinal and systemic inflammation in treated HIV. The large repertoire of inflammatory mediators involved in ADAM17 sheddase activity places it as a pivotal orchestrator of several inflammatory pathways associated with morbidity in chronic treated HIV that make it an attractive therapeutic target. Author summary Novel therapeutic strategies are needed to attenuate increased systemic and gut inflammation that contribute to morbidity and mortality in chronic HIV infection despite potent antiviral therapy. In this study we used preclinical models of chronic HIV (humanized mice and gut tissues from HIV infected persons) to determine whether antioxidant and anti-inflammatory agents called apoA-I mimetic peptides could attenuate systemic and gut inflammation in chronic HIV. Our preclinical data suggest that apoA-I mimetic peptides can target increased levels of a protein called ADAM17 and its proinflammatory activity that contributes to systemic and gut inflammation in HIV. The large repertoire of inflammatory mediators involved in ADAM17 sheddase activity places it as a pivotal orchestrator of several inflammatory pathways associated with morbidity in chronic treated HIV that make it an attractive therapeutic target.

To date, there is no effective oral antiviral against SARS-CoV-2 that is also anti-inflammatory. Herein, we show that the mitochondrial antioxidant mitoquinone/mitoquinol mesylate (Mito-MES), a dietary supplement, has potent antiviral activity against SARS-CoV-2 and its variants of concern in vitro and in vivo . Mito-MES had nanomolar in vitro antiviral potency against the Beta and Delta SARS-CoV-2 variants as well as the murine hepatitis virus (MHV-A59). Mito-MES given in SARS-CoV-2 infected K18-hACE2 mice through oral gavage reduced viral titer by nearly 4 log units relative to the vehicle group. We found in vitro that the antiviral effect of Mito-MES is attributable to its hydrophobic dTPP+ moiety and its combined effects scavenging reactive oxygen species (ROS), activating Nrf2 and increasing the host defense proteins TOM70 and MX1. Mito-MES was efficacious reducing increase in cleaved caspase-3 and inflammation induced by SARS-CoV2 infection both in lung epithelial cells and a transgenic mouse model of COVID-19. Mito-MES reduced production of IL-6 by SARS-CoV-2 infected epithelial cells through its antioxidant properties (Nrf2 agonist, coenzyme Q10 moiety) and the dTPP moiety. Given established safety of Mito-MES in humans, our results suggest that Mito-MES may represent a rapidly applicable therapeutic strategy that can be added in the therapeutic arsenal against COVID-19. Its potential long-term use by humans as diet supplement could help control the SARS-CoV-2 pandemic, especially in the setting of rapidly emerging SARS-CoV-2 variants that may compromise vaccine efficacy.To date, there is no effective oral antiviral against SARS-CoV-2 that is also anti-inflammatory. Herein, we show that the mitochondrial antioxidant mitoquinone/mitoquinol mesylate (Mito-MES), a dietary supplement, has potent antiviral activity against SARS-CoV-2 and its variants of concern in vitro and in vivo . Mito-MES had nanomolar in vitro antiviral potency against the Beta and Delta SARS-CoV-2 variants as well as the murine hepatitis virus (MHV-A59). Mito-MES given in SARS-CoV-2 infected K18-hACE2 mice through oral gavage reduced viral titer by nearly 4 log units relative to the vehicle group. We found in vitro that the antiviral effect of Mito-MES is attributable to its hydrophobic dTPP+ moiety and its combined effects scavenging reactive oxygen species (ROS), activating Nrf2 and increasing the host defense proteins TOM70 and MX1. Mito-MES was efficacious reducing increase in cleaved caspase-3 and inflammation induced by SARS-CoV2 infection both in lung epithelial cells and a transgenic mouse model of COVID-19. Mito-MES reduced production of IL-6 by SARS-CoV-2 infected epithelial cells through its antioxidant properties (Nrf2 agonist, coenzyme Q10 moiety) and the dTPP moiety. Given established safety of Mito-MES in humans, our results suggest that Mito-MES may represent a rapidly applicable therapeutic strategy that can be added in the therapeutic arsenal against COVID-19. Its potential long-term use by humans as diet supplement could help control the SARS-CoV-2 pandemic, especially in the setting of rapidly emerging SARS-CoV-2 variants that may compromise vaccine efficacy.Mitoquinone/mitoquinol mesylate has potent antiviral and anti-inflammatory activity in preclinical models of SARS-CoV-2 infection.One-Sentence SummaryMitoquinone/mitoquinol mesylate has potent antiviral and anti-inflammatory activity in preclinical models of SARS-CoV-2 infection.

AIMS: To determine the prospect of using Electroceuticals as stand-alone or combined treatment regimens so as to surrogate chemical and high-energy non-chemical microbicidal treatments, such as thermal processing. METHODS AND RESULTS: The above hypothesis is tested by a crude Electroculturomics format. Using high and low settings of Intensity and Frequency of alternating current generated by a medical-rated instrument used for TENS therapy, microorganisms were subjected to current while cultured in liquid media. The viability and propagation of seven pathogenic bacteria and one enterovirus of environmental and medical importance were tested in vitro. The treatment was by electrostimulation alone, or combined with mild pasteurization either concurrently or sequentially, against untreated controls. The combined regimen showed mostly synergy, following the prerogatives of the Bioelectric Effect, but occasionally antagonism. High frequency (800Hz) rather than low (2 Hz) seems effective against microbiota; intensity (10 or 1 mA) seems almost inconsequential. But duration is of consequence: longer sessions enhance detrimental effects but short exposure may be beneficial. CONCLUSIONS: Case-specific effects on microbial growth patterns seem to be the norm. No single treatment regimen presents optimal biostatic/biocidal effect for all tested bacteria. High frequency can be effective against low titers of Enterovirus, as it lowers the titer thus suppressing the propagation, but when starting with higher titers, the effect of the treatment may be reversed and the propagation enhanced. SIGNIFICANCE AND IMPACT OF STUDY: To explain the considerable differences in dose-effect curves among different bacteria, diverse mechanisms of both microbicidal and stimulatory activity per species are plausible, as is the case with antibiotics. If so, individualized uses and targeted applications are forthcoming in food and environmental safety, therapeutics and industrial bioprocessing by affecting few species and strains out of a population.Competing Interest StatementThe authors have declared no competing interest.

To date, there is no effective oral antiviral against SARS-CoV-2 that is also anti-inflammatory. Herein, we show that the mitochondrial antioxidant mitoquinone/mitoquinol mesylate (Mito-MES), a dietary supplement, has potent antiviral activity against SARS-CoV-2 and its variants of concern in vitro and in vivo. Mito-MES had nanomolar in vitro antiviral potency against the Beta and Delta SARS-CoV-2 variants as well as the murine hepatitis virus (MHV-A59). Mito-MES given in SARS-CoV-2 infected K18-hACE2 mice through oral gavage reduced viral titer by nearly 4 log units relative to the vehicle group. We found in vitro that the antiviral effect of Mito-MES is attributable to its hydrophobic dTPP+ moiety and its combined effects scavenging reactive oxygen species (ROS), activating Nrf2 and increasing the host defense proteins TOM70 and MX1. Mito-MES was efficacious reducing increase in cleaved caspase-3 and inflammation induced by SARS-CoV2 infection both in lung epithelial cells and a transgenic mouse model of COVID-19. Mito-MES reduced production of IL-6 by SARS-CoV-2 infected epithelial cells through its antioxidant properties (Nrf2 agonist, coenzyme Q10 moiety) and the dTPP moiety. Given established safety of Mito-MES in humans, our results suggest that Mito-MES may represent a rapidly applicable therapeutic strategy that can be added in the therapeutic arsenal against COVID-19. Its potential long-term use by humans as diet supplement could help control the SARS-CoV-2 pandemic, especially in the setting of rapidly emerging SARS-CoV-2 variants that may compromise vaccine efficacy. Competing Interest Statement The authors have declared no competing interest.

The purpose of the study was to investigate the relationship between mindful eating, disordered eating and mood in university students in health-related disciplines. A total of 221 university students participated in the study; 102 students studied sport and exercise science (SS), 54 students pharmacy sciences (PS), and 65 students health sciences (HS). Participants completed the Binge Eating Scale (BES), the Mindful Eating Questionnaire (MEQ), and the Profile of Mood State questionnaire (POMS). 41% of the students were classified as binge eaters and 57% were above the POMS threshold of depression. Binge eaters were found to have significantly lower MEQ score and significantly higher total mood disturbance scores (TMD) compared to non-binge eaters (p < 0.01). Students with a high depression score exhibited no differences in the MEQ score but a significantly higher BES score compared to non-depressed students (p < 0.01). Gender differences were found in the MEQ with females exhibiting significantly higher scores in the MEQ score and in all MEQ subscales compared to males, with the exception of the emotional subscale that females were noted to have a lower score compared to males (p < 0.01). The MEQ score was inversely related to the BES score (r = −0.30, p < 0.01) and TMD (r = −0.21, p < 0.05). The MEQ score was a significant negative predictor of the variance of the binge eating behavior of the students (B = −3.17, p < 0.001). In conclusion, mindfulness in eating is inversely related to the binge eating behavior and mood state of university students studying health-related subjects and is a significant negative predictor of disordered eating behavior in this high risk population.

PurposeThe paper aims to explore the effects of the behavioural antecedents suggested by the theory of planned behaviour (TPB) (i.e. positive subjective norms, high perceived behavioural control and positive attitudes towards switching) on the switching propensity of retail banking customers at several critical switching incidents (CSIs) (i.e. events of unfavourable reputation concerning their current bank or favourable reputation concerning competitor banks, service failures, problems with charges and interest rates, herding behaviour, inconvenience, alternative banks' attractiveness and unethical bank practices).Design/methodology/approachA self-completed online survey was conducted among 324 Cypriot retail banking customers. For the data analysis, the researchers used principal component analysis (PCA), confirmatory factor analysis (CFA) and structural equation modelling (SEM).FindingsThe study revealed that the behavioural antecedents specified by TPB play different roles in various CSIs. Positive subjective norms may drive bank customers to switch at critical incidents such as: service failure, unfavourable bank reputation, alternative banks' attractiveness, inconvenience, favourable reputation of other banks and herding behaviour. High perceived behavioural control can lead to switching, only in the case of other banks' favourable reputation. Finally, positive attitudes towards switching may affect bank clients to switch in cases of service failure, unfavourable bank reputation, alternative attractiveness and inconvenience.Originality/valueTo the best of the authors' knowledge, no other previous research work has examined the interaction between the antecedents of switching behaviour (as specified by TPB) and switching propensity at different CSIs. The study addresses the gap of explaining the reasons for which, at similar incidents, some bank customers choose to switch to other banks, whereas others do not.