Prussian Blue@Zeolitic imidazolate framework composite toward solar-triggered biodecontamination

Metal-organic frameworks (MOFs) featuring composition and bandstructure diversity, are an emerging class of photoresponsive disinfectants. In this study, we demonstrated the superiority of core–shell arranged photoactive MOFs (prussian blue (PB) and zeolitic imidazolate framework (ZIF-8)) for pathogen inactivation in terms of biocidal efficiency and broad-spectrum sensitivity. Reactive oxygen species (ROS) production was significantly promoted after the integration of PB due to the photosensitization effect and initiation of in situ Fenton reaction. Favorably, another inactivation channel was also opened owing to the unique photothermal effect of PB. Attributed to the facilitated ROS intracellular penetration by heat, the composite outperforms not only individual component but anatase TiO2 in pathogen elimination. Specifically, the Staphylococcus aureus (S. aureus) inactivation efficiency of the composite (6.6 log) is 2, 1.8 and 5.1 times higher than that of PB (3.3 log), ZIF-8 (3.7 log) and TiO2 (1.3 log) over 45 min of simulated sunlight illumination. Significantly, the infectivity of Bacillus anthracis and murine coronavirus in droplets on composite-coated filter surface could be greatly reduced (approximately 3 log reduction in colony number/coronavirus titer) within few minutes of solar exposure, indicative of the great potential of MOF composites toward life-threatening microbial infection prevention. © 2022 Elsevier B.V.

Antimicrobial photodynamic therapy and the advances impacted by the association with nanoparticles

Microbial resistance to antibiotics, antifungals, and virucides is one of today's most significant public health problems. Antimicrobial Photodynamic Therapy (aPDT) is a prominent therapeutic strategy for infection control that does not cause microbial resistance to treatment. Its microbial eradication potential is significantly increased when aPDT is associated with nanotechnology. aPDT causes cell death due to photophysical and photochemical events derived from the interaction between a photosensitive agent (PS), a light at an appropriate wavelength, and the oxygen in the medium. Its main product, reactive oxygen species (ROS), leads to the death of microorganisms in and around the irradiated PS. However, the low water solubility, instability, and low microbial internalization of PSs with high quantum yield diminish the effectiveness of the aPDT. Nanoparticles emerge to overcome these limitations. They have been shown to increase the photodynamic activity of PSs and potentially target their delivery to infected sites, increasing the selectivity of the therapy. This review addresses the main constraints of bacteria, fungi, and viruses to the effectiveness of aPDT and discusses how nanotechnology can overcome these difficulties. Current studies that used polymeric, lipid, and metallic nanoparticles associated with aPDT were raised, and the significant advances impacted by them were critically discussed. Among the microorganisms eliminated by nanoparticles-associated aPDT, Methicillin-Resistant Staphylococcus aureus (MRSA) bacteria in planktonic culture and the form of biofilms, and fungi such as Candida albicans, stand out. The nanoparticle-associated aPDT increases the chances of success of oral cavity treatments, such as those that affect the root canal, and cutaneous, such as dermatophytosis. The use of aPDT against viruses such as HSV-1 and HIV, including Sars-CoV-2, has also shown promising results. The selectivity and effectiveness of aPDT are strictly related to the characteristics of the PS-loaded nanoparticle. It is essential to know the microorganism and the place it is installed to select the nanocarrier properly. © 2023 Elsevier B.V.

Recent advances of nanotechnology in COVID 19: A critical review and future perspective

The global anxiety and economic crisis causes the deadly pandemic coronavirus disease of 2019 (COVID 19) affect millions of people right now. Subsequently, this life threatened viral disease is caused due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, morbidity and mortality of infected patients are due to cytokines storm syndrome associated with lung injury and multiorgan failure caused by COVID 19. Thereafter, several methodological advances have been approved by WHO and US-FDA for the detection, diagnosis and control of this wide spreadable communicable disease but still facing multi-challenges to control. Herein, we majorly emphasize the current trends and future perspectives of nano-medicinal based approaches for the delivery of anti-COVID 19 therapeutic moieties. Interestingly, Nanoparticles (NPs) loaded with drug molecules or vaccines resemble morphological features of SARS-CoV-2 in their size (60–140 nm) and shape (circular or spherical) that particularly mimics the virus facilitating strong interaction between them. Indeed, the delivery of anti-COVID 19 cargos via a nanoparticle such as Lipidic nanoparticles, Polymeric nanoparticles, Metallic nanoparticles, and Multi-functionalized nanoparticles to overcome the drawbacks of conventional approaches, specifying the site-specific targeting with reduced drug loading and toxicities, exhibit their immense potential. Additionally, nano-technological based drug delivery with their peculiar characteristics of having low immunogenicity, tunable drug release, multidrug delivery, higher selectivity and specificity, higher efficacy and tolerability switch on the novel pathway for the prevention and treatment of COVID 19. © 2022 The Author(s)

Animal Models, Zoonotic Reservoirs, and Cross-Species Transmission of Emerging Human-Infecting Coronaviruses.

Over the past three decades, coronavirus (CoV) diseases have impacted humans more than any other emerging infectious disease. The recent emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19 (coronavirus disease 2019), has resulted in huge economic disruptions and loss of human lives. The SARS-CoV-2 genome was found to mutate more rapidly due to sustained transmission in humans and potentially animals, resulting in variants of concern (VOCs) that threaten global human health. However, the primary difficulties are filling in the current knowledge gaps in terms of the origin and modalities of emergence for these viruses. Because many CoVs threatening human health are suspected to have a zoonotic origin, identifying the animal hosts implicated in the spillover or spillback events would be beneficial for current pandemic management and to prevent future outbreaks. In this review, wesummarize the animal models, zoonotic reservoirs, and cross-species transmission of the emerging human CoVs. Finally, we comment on potential sources of SARS-CoV-2 Omicron VOCs and the new SARS-CoV-2 recombinants currently under investigation.

Convergent Evolution Dynamics of SARS-CoV-2 and HIV Surface Envelope Glycoproteins Driven by Host Cell Surface Receptors and Lipid Rafts: Lessons for the Future.

Although very different, in terms of their genomic organization, their enzymatic proteins, and their structural proteins, HIV and SARS-CoV-2 have an extraordinary evolutionary potential in common. Faced with various selection pressures that may be generated by treatments or immune responses, these RNA viruses demonstrate very high adaptive capacities, which result in the continuous emergence of variants and quasi-species. In this retrospective analysis of viral proteins, ensuring the adhesion of these viruses to the plasma membrane of host cells, we highlight many common points that suggest the convergent mechanisms of evolution. HIV and SARS-CoV-2 first recognize a lipid raft microdomain that acts as a landing strip for viral particles on the host cell surface. In the case of mucosal cells, which are the primary targets of both viruses, these microdomains are enriched in anionic glycolipids (gangliosides) forming a global electronegative field. Both viruses use lipid rafts to surf on the cell surface in search of a protein receptor able to trigger the fusion process. This implies that viral envelope proteins are both geometrically and electrically compatible to the biomolecules they select to invade host cells. In the present study, we identify the surface electrostatic potential as a critical parameter controlling the convergent evolution dynamics of HIV-1 and SARS-CoV-2 surface envelope proteins, and we discuss the impact of this parameter on the phenotypic properties of both viruses. The virological data accumulated since the emergence of HIV in the early 1980s should help us to face present and future virus pandemics.

Dysfunctional mitochondrial processes contribute to energy perturbations in the brain and neuropsychiatric symptoms.

Mitochondria are complex endosymbionts that evolved from primordial purple nonsulfur bacteria. The incorporation of bacteria-derived mitochondria facilitates a more efficient and effective production of energy than what could be achieved based on previous processes alone. In this case, endosymbiosis has resulted in the seamless coupling of cytochrome c oxidase and F-ATPase to maximize energy production. However, this mechanism also results in the generation of reactive oxygen species (ROS), a phenomenon that can have both positive and negative ramifications on the host. Recent studies have revealed that neuropsychiatric disorders have a pro-inflammatory component in which ROS is capable of initiating damage and cognitive malfunction. Our current understanding of cognition suggests that it is the product of a neuronal network that consumes a substantial amount of energy. Thus, alterations or perturbations of mitochondrial function may alter not only brain energy supply and metabolite generation, but also thought processes and behavior. Mitochondrial abnormalities and oxidative stress have been implicated in several well-known psychiatric disorders, including schizophrenia (SCZ) and bipolar disorder (BPD). As cognition is highly energy-dependent, we propose that the neuronal pathways underlying maladaptive cognitive processing and psychiatric symptoms are most likely dependent on mitochondrial function, and thus involve brain energy translocation and the accumulation of the byproducts of oxidative stress. We also hypothesize that neuropsychiatric symptoms (e.g., disrupted emotional processing) may represent the vestiges of an ancient masked evolutionary response that can be used by both hosts and pathogens to promote self-repair and proliferation via parasitic and/or symbiotic pathways.

A Qualitative Analysis of Management Perspectives on Seeking to Implement the Foster Cat Project in Residential Aged Care in the Context of COVID-19.

This study explores the challenges facing a pilot project aiming to foster homeless cats in an Australian residential aged care facility. The global COVID-19 pandemic stalled the project but also presented an opportunity to gain reflective insights into the perceived barriers, enablers and tensions involved in seeking to implement pet animal inclusion in residential aged care. Perspectives from aged care management, animal welfare services and researchers/project managers were all sought using semi-structured interviews, and themes developed using a qualitative descriptive analysis. Perceived barriers to the project before and after the pandemic were not dissimilar with four key themes emerging: competing priorities, risk and safety, resources, and timing. All existed differently across stakeholder groups creating tensions to be negotiated. These themes are then mapped to the competencies established by the International Union of Health Promotion and Education (IUHPE) for undertaking health promotion, demonstrating that this skill base can be drawn on when seeking to implement human-animal inclusive projects. Creating supportive healthful environments for frail older persons is a moral imperative of extended lives. Health Promotion skills as outlined in the Ottawa Charter and IUHPE competencies for health promotion workers need to be extended to include animal services, agendas and cultures to promote multi-species health promotion into the future.

Efficiency of ant-control agents in colony-level oral toxicity tests using Tetramorium tsushimae (Hymenoptera: Formicidae) for post-establishment control of the red imported fire ant, Solenopsis invicta (Hymenoptera: Formicidae).

The red imported fire ant Solenopsis invicta Buren (Hymenoptera: Formicidae) causes serious damage worldwide as an invasive alien species. The species has expanded its range to the Pacific Rim since 2000s and Japan has faced its multiple introductions since 2017. While colony-level control methods are urgently needed, testing living colonies of the unestablished species is challenging especially due to various restrictions under the COVID-19 pandemic. Here, we proposed alternative long-term toxicity assays using artificial colonies of Tetramorium tsushimae Emery (Hymenoptera: Formicidae), a Japanese native species belonging to the same subfamily (Myrmicinae) as S. invicta. We conducted an acute toxicity test to determine if T. tsushimae is a suitable substitute for S. invicta using fipronil and found the LD50 value in T. tsushimae was close to that in S. invicta. Then, we conducted the long-term toxicity test with fipronil and two insect growth regulators (pyriproxyfen and etoxazole) using artificial colonies of T. tsushimae. All workers and larvae in the fipronil-treated colonies died within 3 days of treatment initiation. Emergence of new workers was observed after 18 days in the etoxazole-treated and control colonies, but not in the pyriproxyfen-treated colonies. We concluded that fipronil was the most promising insecticide for post-establishment control, and pyriproxyfen was effective as a toxic-bait agent for colony-level control. Supplementary Information: The online version contains supplementary material available at 10.1007/s13355-022-00800-x.

Uncovering novel disinfection mechanisms of solar light/periodate system: The dominance of singlet oxygen and metabolomic insights

Disinfection plays an essential role in waterborne pathogen control and disease prevention, especially during the COVID-19 pandemic. Catalyst-free solar light/periodate (PI) system has recently presented great potential in water disinfection, whereas the in-depth chemical and microbiological mechanisms for efficient bacterial inactivation remain unclear. Our work delineated firstly the critical role of singlet oxygen, instead of reported hydroxyl radicals and superoxide radicals, in dominating bacterial inactivation by the PI/simulated sunlight (SSL) system. Multi-evidence demonstrated the prominent disinfection performance of this system for Staphylococcus aureus in terms of culturability (> 6 logs CFU), cellular integrity, and metabolic activity. Particularly, the excellent intracellular DNA removal (> 95%) indicated that PI/SSL system may function as a selective disinfection strategy to diminish bacterial culturability without damaging the cell membrane. The PI/SSL system could also effectively inhibit bacterial regrowth for > 5 days and horizontal gene transfer between E. coli genera. Nontargeted metabolomic analysis suggested that PI/SSL system inactivated bacteria by triggering the accumulation of intracellular reactive oxygen species and the depletion of reduced glutathione. Additionally, the PI/SSL system could accomplish simultaneous micropollutant removal and bacterial inactivation, suggesting its versatility in water decontamination. Overall, this study deciphers more comprehensive antibacterial mechanisms of this environmentally friendly disinfection system, facilitating the technical development and application of the selective disinfection strategy in environmental pathogen control. [Display omitted] • PI/SSL system selectively inactivates cells by targeting intracellular DNA first. • PI/SSL treatment inhibits bacterial regrowth and horizontal gene transfer potential. • The bactericidal effect of 1O 2 in PI/SSL system was proposed for the first time. • Metabolomics showed that ROS accumulation is one of the antibacterial mechanisms. • PI/SSL system holds great promise in decontamination of the actual water system. [ FROM AUTHOR]

A Brief Review on Guduchi (Tinospora Cordifolia)

Guduchi (Tinospora cordifolia) is an essential drug of the Ayurvedic medicine system used in different Ayurvedic formulations to treat a variety of ailments. Guduchi is a member of the Menispermaceae family and is widely produced in tropical and sub-tropical countries such as India, Sri Lanka, China, Myanmar, Philippines, South Africa, Thailand, Bangladesh, and several south-east Asian continents such as Indonesia, Malaysia. All parts of Guduchi have nutritional value and medicinal importance, including the roots, stem, bark, and leaves. A different class of phytochemicals like alkaloids, glycosides, aliphatic compounds, diterpenoids, sesquiterpenoids, phenolic compounds, steroid and polysaccharides, etc., are found in Guduchi. Tinosporaside, tinosporine, magnosporine, berberine, choline, Jatrorrhizine, palmatine, beberine, giloin, giloinsterol, and other beneficial biomarkers are present in this herb. Guduchi is used to treat cold, fever, headache, jaundice, digestive disorder, among other things, and it shows several proven pharmacological activities such as anti-oxidant, anti-inflammatory, antidiabetic, immunomodulatory activity, anti-toxic, hepatoprotective, anticancer, cardioprotective activity, radioprotective, antimicrobial, anti-stress, anti-HIV and many more. This review article majorly highlights the phytochemical present in Guduchi, analytical works and pharmacological activities of Guduchi. Copyright © 2022 are reserved by International Journal of Pharmaceutical Sciences and Research.

Responding to crises: rewilding accounting education for the Anthropocene

PurposeResponding to COVID-19, this conceptual paper uses rewilding to interrupt anthropocentric and human/nature dualist properties of accounting education. Through rewilding accounting education, informed by posthumanist and ecofeminist thought, this paper aims to develop an accounting pedagogy that shapes greater ecocentric narratives. Accounting educators can contribute to addressing crises by evolving new pedagogies that radically transform the education of future accounting professionals.Design/methodology/approachThe authors take a critical stance in analysing the human-centred accounting education model. They explore how this model can be reimagined through rewilding accounting education, resulting in learning interventions that foster an understanding of intrinsic value, complexity of systems and collective disposition with all species and the natural world.FindingsRewilding learning interventions embed an ecocentric approach in accounting curricula design to extend beyond a human focus. Rewilding learning interventions practically explored with application to accounting include learning with and from nature, Indigenous knowledge perspectives, play as a common language and empathy as a dialogical bridge.Social implicationsThe authors present an accounting pedagogy that fosters among accounting students and educators a relational orientation and ecological consciousness that encompasses compassion and openness to others, including non-human species and nature. This will ensure that accounting graduates are better prepared for addressing future crises that stem from our disconnect with nature.Originality/valueThis paper adds to limited research investigating accounting and the Anthropocene. Investigations into the Anthropocene's human-centred discourse in accounting education are vital to respond adequately to crises. This paper extends social and environmental accounting education literature to encompass less anthropocentric discourse and greater relational learning.

The Threat of Potentially Pathogenic Bacteria in the Feces of Bats.

Bats have attracted global attention because of their zoonotic association with severe acute respiratory syndrome coronavirus (SARS-CoV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Previous and ongoing studies have predominantly focused on bat-borne viruses; however, the prevalence or abundance of bat-borne pathogenic bacteria and their potential public health significance have largely been neglected. For the first time, this study used both metataxonomics (16S rRNA marker gene sequencing) and culturomics (traditional culture methods) to systematically evaluate the potential public health significance of bat fecal pathogenic bacteria. To this end, fecal samples were obtained from five bat species across different locations in China, and their microbiota composition was analyzed. The results revealed that the bat microbiome was most commonly dominated by Proteobacteria, while the strictly anaerobic phylum Bacteroidetes occupied 35.3% of the relative abundance in Rousettus spp. and 36.3% in Hipposideros spp., but less than 2.7% in the other three bat species (Taphozous spp., Rhinolophus spp., and Myotis spp.). We detected 480 species-level phylotypes (SLPs) with PacBio sequencing, including 89 known species, 330 potentially new species, and 61 potentially higher taxa. In addition, a total of 325 species were identified by culturomics, and these were classified into 242 named species and 83 potentially novel species. Of note, 32 of the 89 (36.0%) known species revealed by PacBio sequencing were found to be pathogenic bacteria, and 69 of the 242 (28.5%) known species isolated by culturomics were harmful to people, animals, or plants. Additionally, nearly 40 potential novel species which may be potential bacterial pathogens were identified. IMPORTANCE Bats are one of the most diverse and widely distributed groups of mammals living in close proximity to humans. In recent years, bat-borne viruses and the viral zoonotic diseases associated with bats have been studied in great detail. However, the prevalence and abundance of pathogenic bacteria in bats have been largely ignored. This study used high-throughput sequencing techniques (metataxonomics) in combination with traditional culture methods (culturomics) to analyze the bacterial flora in bat feces from different species of bats in China, revealing that bats are natural hosts of pathogenic bacteria and carry many unknown bacteria. The results of this study can be used as guidance for future investigations of bacterial pathogens in bats.

Cucurbitaceae species used as traditional medicine in West Africa

Background: The use of some Cucurbitaceae species for the treatment of diseases is an ancient practice in traditional medicine systems in Africa and the cucurbitacins among others have been reported to be responsible for most of these healing activities. Aim: This review discusses the relevance of Cucurbitaceae species in traditional medicine in some west African countries. Methods: A literature search was conducted on electronic databases such as Google Books, Google Scholar, Scopus and Web of Science. The search involved the use of several terms and free text words which include 'Cucurbitaceae species in West Africa traditional medicine';'medicinal plants of the Cucurbitaceae family used to treat diseases in west African communities'. Results: Several Cucurbitaceae species are used in the region either in similar ways or different ways for the treatment of different diseases. The leaves are the most utilised plant parts and decoctions are the most common method of preparation. From this study, 18 species of Cucurbitaceae used for medicinal purposes were reviewed from Nigeria;4 from Benin, Ghana, Côte d'Ivoire and Mali, respectively;1 from Togo;5 from Senegal;9 from Cameroon and 3 from Gabon and Burkina Faso, respectively. Momordica charantia and Momordica balsamina are often utilised for abortion in some west African countries. Momordica species and Lagenaria breviflora are utilised to treat diabetes, cough related to respiratory infections and viral infections such as measles and chickenpox Conclusions: In-depth research into these plants could help to develop a natural, novel cure for diabetes and coronavirus (COVID-19) and effective, cheap contraceptive. Contribution: This review highlights the significant role of Cucurbitaceae species in the treatment of a wide range of diseases and health issues in the WestAfrican traditional medicine system. The information provided could be used as a guide by research scientists for the formulation of natural products to cure a variety of diseases. © 2022. The Authors.

Generation and Characterization of a SARS-CoV-2-Susceptible Mouse Model Using Adeno-Associated Virus (AAV6.2FF)-Mediated Respiratory Delivery of the Human ACE2 Gene.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the aetiological agent of coronavirus disease 2019 (COVID-19) that has caused a pandemic with millions of human infections. There continues to be a pressing need to develop potential therapies and vaccines to inhibit SARS-CoV-2 infection to mitigate the ongoing pandemic. Epidemiological data from the current pandemic indicates that there may be sex-dependent differences in disease outcomes. To investigate these differences, we proposed to use common small animal species that are frequently used to model disease with viruses. However, common laboratory strains of mice are not readily infected by SARS-CoV-2 because of differences in the angiotensin-converting enzyme 2 (ACE2), the cellular receptor for the virus. To overcome this limitation, we transduced common laboratory accessible strains of mice of different sexes and age groups with a novel a triple AAV6 mutant, termed AAV6.2FF, encoding either human ACE2 or luciferase via intranasal administration to promote expression in the lung and nasal turbinates. Infection of AAV-hACE2-transduced mice with SARS-CoV-2 resulted in high viral titers in the lungs and nasal turbinates, establishment of an IgM and IgG antibody response, and modulation of lung and nasal turbinate cytokine profiles. There were insignificant differences in infection characteristics between age groups and sex-related differences; however, there were significant strain-related differences between BALB/c vs. C57BL/6 mice. We show that AAV-hACE2-transduced mice are a useful for determining immune responses and for potential evaluation of SARS-CoV-2 vaccines and antiviral therapies, and this study serves as a model for the utility of this approach to rapidly develop small-animal models for emerging viruses.

Cross-species transmission, evolution and zoonotic potential of coronaviruses.

Coronaviruses (CoVs) continuously evolve, crossing species barriers and spreading across host ranges. Over the last two decades, several CoVs (HCoV-229E, HCoV-NL63, HCoV-HKU1, HCoV-OC43, SARS-CoV, MERS-CoV, and SARS-CoV-2) have emerged in animals and mammals, causing significant economic and human life losses. Due to CoV cross-species transmission and the evolution of novel viruses, it is critical to identify their natural reservoiurs and the circumstances under which their transmission occurs. In this review, we use genetic and ecological data to disentangle the evolution of various CoVs in wildlife, humans, and domestic mammals. We thoroughly investigate several host species and outline the epidemiology of CoVs toward specific hosts. We also discuss the cross-species transmission of CoVs at the interface of wildlife, animals, and humans. Clarifying the epidemiology and diversity of species reservoirs will significantly impact our ability to respond to the future emergence of CoVs in humans and domestic animals.

Interplay between swine enteric coronaviruses and host innate immune.

Swine enteric coronavirus (SeCoV) causes acute diarrhea, vomiting, dehydration, and high mortality in neonatal piglets, causing severe losses worldwide. SeCoV includes the following four members: transmissible gastroenteritis virus (TGEV), porcine epidemic diarrhea virus (PEDV), porcine delta coronavirus (PDCoV), and swine acute diarrhea syndrome coronavirus (SADS-CoV). Clinically, mixed infections with several SeCoVs, which are more common in global farms, cause widespread infections. It is worth noting that PDCoV has a broader host range, suggesting the risk of PDCoV transmission across species, posing a serious threat to public health and global security. Studies have begun to focus on investigating the interaction between SeCoV and its host. Here, we summarize the effects of viral proteins on apoptosis, autophagy, and innate immunity induced by SeCoV, providing a theoretical basis for an in-depth understanding of the pathogenic mechanism of coronavirus.

Current status of industrialized aquaculture in China: a review.

Industrialized aquaculture is an essential trend for aquaculture development in China, owing to its considerable advantages in lower water consumption, higher productivity, and sustainability. However, information on its current status has been scarce up to now. This paper reviewed the current status and has identified existing problems as well as proposing possible solutions for the development of industrialized aquaculture in China. This field is still at an early stage of development and is mainly distributed in coastal regions. Major constraints on industrialized aquaculture include high capital and operational costs, the uncompetitive market price of aquatic products, uneven distribution of production and farming areas, a lack of suitably experienced managers and operators for recirculating aquaculture systems, and the coronavirus disease 2019 (COVID-19) pandemic. Possible solutions to these problems include technological innovations in systems optimization, the use of renewable energy sources and biofloc technology, the pollution-free certification of industrial aquaculture products, increased numbers of professionals in water quality control and waste management, and the financial assistance to companies and farmers along the aquaculture industrial chain.

Inhibition of IL-6 signaling prevents serum-induced umbilical cord artery dysfunction from patients with severe COVID-19.

Coronavirus disease 2019 (COVID-19) infection has a negative impact on the cytokine profile of pregnant women. Increased levels of proinflammatory cytokines seem to be correlated with the severity of the disease, in addition to predisposing to miscarriage or premature birth. Proinflammatory cytokines increase the generation of reactive oxygen species (ROS). It is unclear how interleukin-6 (IL-6) found in the circulation of patients with severe COVID-19 might affect gestational health, particularly concerning umbilical cord function. This study tested the hypothesis that IL-6 present in the circulation of women with severe COVID-19 causes umbilical cord artery dysfunction by increasing ROS generation and activating redox-sensitive proteins. Umbilical cord arteries were incubated with serum from healthy women and women with severe COVID-19. Vascular function was assessed using concentration-effect curves to serotonin in the presence or absence of pharmacological agents, such as tocilizumab (antibody against the IL-6 receptor), tiron (ROS scavenger), ML171 (Nox1 inhibitor), and Y27632 (Rho kinase inhibitor). ROS generation was assessed by the dihydroethidine probe and Rho kinase activity by an enzymatic assay. Umbilical arteries exposed to serum from women with severe COVID-19 were hyperreactive to serotonin. This effect was abolished in the presence of tocilizumab, tiron, ML171, and Y27632. In addition, serum from women with severe COVID-19 increased Nox1-dependent ROS generation and Rho kinase activity. Increased Rho kinase activity was abolished by tocilizumab and tiron. Serum cytokines in women with severe COVID-19 promote umbilical artery dysfunction. IL-6 is key to Nox-linked vascular oxidative stress and activation of the Rho kinase pathway.