Progress in understanding the health promoting effect of egg yolk immunoglobulin

As an important immuneoactive component in eggs, yolk immunoglobulin (IgY) shows great competitiveness in research and production due to its good stability, high safety, low cost, easy availability, strong immune activity, and no drug resistance. This article highlights the significant advantages of IgY as a good antibiotic substitute in the prevention and treatment of viral and bacterial diseases. Also, IgY has great potential in the regulation of nutrient metabolism balance, intestinal microflora and immune homeostasis by affecting key rate-limiting enzymes, and relevant receptors and inflammatory factors specifically. Proper diet and targeted delivery of foodborne IgY may be a new perspective on inflammation regulation, disease control, nutritional balance or homeostasis, and oral microencapsulated IgY is expected to be a new approach against increasing public health emergencies (such as COVID-19 pandemic).

Function and interaction of coronavirus ion channel proteins

Objective: COVID-19 has emerged as a significant global health crisis causing devastating effects on world population accounting for over 6 million deaths worldwide. Although acute RTI is the prevalent cause of morbidity, kidney outcomes centered on a spectrum of AKI have evolved over the course of the pandemic. Especially the emerging variants have posed a daunting challenge to the scientific communities, prompting an urging requirement for global contributions in understanding the viral dynamics. In addition to canonical genes, several subgroup- specific accessory genes are located between the S and E genes of coronaviruses regarding which little is known. Previous studies have shown that accessory proteins (aps) in viruses function as viroporins that regulate viral infection, propagation and egress [1]. In this study we attempted to characterize the function of aps of coronavirus variants as ion channels. Furthermore, we also probed the interaction of ap4 with the host system. Method(s): Serial passaging (selection pressure), growth kinetics, confocal imaging, genome sequence analysis and proteomics were performed in Huh-7, MRC5 cells and/or human monocyte derived macrophages. Potassium uptake assay was performed in a Saccharo myces cerevisiae strain, which lacks the potassium transporters trk1 and trk2. Ion conductivity experiments were performed in Xenopus laevis oocytes using Two Electrode Voltage Clamp (TEVC) method. Result(s): Serial passaging demonstrated the acquisition of several frameshift mutations in ORF4 resulting in C-terminally truncated protein versions (ap4 and ap4a) and indicate a strong selection pressure against retaining a complete ORF4 in vitro. Growth kinetics in primary cells illustrated a reduction of viral titers when the full-length ap4 was expressed compared to the C-terminally truncated protein ap4a. Confocal imaging showed that ap4 and ap4a are not exclusively located in a single cellular compartment. Potassium uptake assay in yeast and TEVC analyses in Xenopus oocytes showed that ap4 and ap4a act as a weak K+ selective ion channel. In addition, accessory proteins of other virus variants also elicited microampere range of currents. Conclusion(s): Our study provides the first evidence that ap4 and other accessory proteins of coronavirus variants act as viroporins. Future studies are aimed at demonstrating the role of ap4 during the viral life cycle by modulating ion homeostasis of host cell in vivo (interacting proteins obtained from proteomic studies) and thereby serve as a tool for potential drug target.

Boosting the Immune System with Vitamin D: Special Focus on Prevention of COVID-19 and Complications

In addition to the classical functions of the musculoskeletal system and calcium homeostasis, the function of vitamin D as an immune modulator is well established. The vitamin D receptors and enzymes that metabolize vitamin D are ubiquitously expressed in most cells in the body, including T and B lymphocytes, antigen-presenting cells, monocytes, macrophages and natural killer cells that trigger immune and antimicrobial responses. Many in vitro and in vivo studies revealed that vitamin D promotes tolerogenic immunological action and immune modulation. Vitamin D adequacy positively influences the expression and release of antimicrobial peptides, such as cathelicidin, defensin, and anti-inflammatory cytokines, and reduces the expression of proinflammatory cytokines. Evidence suggestss that vitamin D's protective immunogenic actions reduce the risk, complications, and death from COVID-19. On the contrary, vitamin D deficiency worsened the clinical outcomes of viral respiratory diseases and the COVID-19-related cytokine storm, acute respiratory distress syndrome, and death. The study revealed the need for more preclinical studies and focused on well-designed clinical trials with adequate sizes to understand the role of vitamin D on the pathophysiology of immune disorders and mechanisms of subduing microbial infections, including COVID-19.Copyright © 2023 Bentham Science Publishers.

Clinical and Epidemiological Characteristics of COVID-19 in Persons Living with HIV Complicated by Tuberculosis

Relevance. At present, three infections – HIV infection, tuberculosis, and COVID-19-are spreading simultaneously in the world. Of great practical importance is the assessment of clinical and epidemiological features of COVID-19 in HIV-infected patients with tuberculosis, COVID-19. Aim. To study the risk of COVID-19 disease and identify clinical and epidemiological features in and population of patients with HIV infection complicated by tuberculosis in comparison with patients with HIV infection and the population without these diseases. Materials and methods. Since 13.03.2020 by 31.12.2021 in the Kemerovo Region-Kuzbass, a continuous prospective analytical epidemiological study of the case-control type was performed. Of those with COVID-19, two observation groups were formed: group I (HIV +), group II (HIV/TB) and comparison group III (persons without either HIV or tuberculosis). All patients underwent: determination of SARS-CoV-2 RNA, standard examination methods in accordance with the temporary methodological recommendations «Prevention, diagnosis and treatment of a new coronavirus infection (COVID-19)», relevant at the time of treatment. Results. The incidence of COVID-19 among patients with HIV infection complicated by tuberculosis exceeded the incidence of COVID-19 among HIV-infected by 14%. There were no gender differences between patients I (HIV +) and II (HIV/TB) groups. In the comparison group, the incidence of COVID-19 was 1.26 times higher in women compared to men. COVID-19 disease in patients with co-infection (HIV/TB) was predominantly mild. Viral pneumonia developed 1.86 times less often, oxygenotherapy was required only in 18.75% of cases, which is 2.5 times lower than in group I (HIV +) and 2.47 times less than in the comparison group (III). In labeled pairs, clinical symptoms of COVID-19 in all groups occurred with the same frequency. Metabolic disorders were evident in all groups. Co-infected patients (HIV/TB) had higher levels of D-dimer, ESR, total bilirubin. Conclusion. Active tuberculosis in HIV-infected people is a factor that increases the risk of COVID-19 disease without affecting the severity of the infectious process. © 2023, Numikom. All rights reserved.

SARS-CoV-2 infection disrupts trophoblast function and placental syncytial barrier integrity via its accessory protein, ORF3a

Problem: Although it is rare for a SARS-CoV-2 infection to transmit vertically to the fetus during pregnancy, there is a significantly increased risk of adverse pregnancy outcomes due to maternalCOVID- 19. However, there is a poor understanding of such risks because mechanistic studies on how SARS-CoV-2 infection disrupts placental homeostasis are significantly lacking. The SARS-CoV-2 proteome includes multiple structural and non-structural proteins, including the non-structural accessory proteinORF3a. The roles of these proteins in mediating placental infection remain undefined. We and others have shown that autophagy activity in placental syncytium is essential for barrier function and integrity. Here, we have used clinical samples and cultured trophoblast cells to evaluate syncytial integrity of placenta exposed to SARS-CoV-2. The objective of our study was to investigate potential mechanisms through which SARS-CoV-2 impairs placental homeostasis and causes adverse pregnancy outcomes. We tested the central hypothesis that an essential SARS-CoV-2 non-structural and accessory protein, ORF3a, uniquely (amongst multiple viral proteins tested) with a novel three-dimensional structure andwith no homology to any other proteins is a key modulator of placental trophoblast cell dynamics via autophagy and intracellular trafficking of a tight junction protein (TJP), ZO-1. Method(s): We used clinical samples and cultured trophoblast cells to evaluate syncytial integrity of placentas exposed to SARS-CoV- 2. Autophagic flux was measured in placental villous biopsies from SARS-CoV-2-exposed and unexposed pregnant women by quantifying the expression of autophagy markers, LC3 and P62. Trophoblast cells (JEG-3, Forskolin-treated JEG-3, HTR8/SVneo, or primary human trophoblasts (PHTs)) were transfected with expression plasmids encoding SARS-CoV-2 proteins including ORF3a. Using western blotting, multi-label immunofluorescence, and confocal imaging, we analyzed the effect of ORF3a on the autophagy, differentiation, invasion, and intracellular trafficking of ZO-1 in trophoblasts. Using coimmunoprecipitation assays, we tested ORF3a interactions with host proteins. t-tests and one-way analyses of variance (ANOVAs) with post hoc tests were used to assess the data, with significance set at P < .05. Result(s): We discovered :1) increased activation of autophagy, but incomplete processing of autophagosome-lysosomal degradation;2) accumulation of protein aggregates in placentas exposed to SARS-CoV- 2. Mechanistically, we showed that the SARS-CoV-2 ORF3a protein, uniquely 3) blocks the autophagy-lysosomal degradation process;4) inhibits maturation of cytotrophoblasts into syncytiotrophoblasts (STBs);5) reduces production ofHCG-beta, a key pregnancy hormone that is also essential for STB maturation;and 6) inhibits trophoblast invasive capacity. Furthermore, ORF3a harbors an intrinsically disordered C-terminus withPDZ-bindingmotifs.We show for the first time that, 7) ORF3a binds to and co-localizes with the PDZ domain of ZO-1, a junctional protein that is essential for STB maturation and the integrity of the placental barrier. Conclusion(s): Our work outlines a new molecular and cellular mechanism involving the SARS-CoV-2 accessory protein ORF3a that may drive the virus's ability to infect the placenta and damage placental syncytial integrity. This implies that the mechanisms facilitating viral maturation, such as the interaction of ORF3a with host factors, can be investigated for additional functionality and even targeted for developing new intervention strategies for treatment or prevention of SARS-CoV-2 infection at the maternal-fetal interface.

FACTORS CONTRIBUTING TO THE NEW CORONAVIRUS INFECTION, INCREASED RISK OF COMPLICATIONS AND DEATH FROM IT IN THE ARMED FORCES OF THE RUSSIAN FEDERATION

Based on the assessment of factors that contribute to a new coronavirus infection, the risk of complications, mortality, and lethality from it in the Armed Forces of the Russian Federation were analyzed. A detailed timeline of the development of the coronavirus pandemic in the Russian Federation has been demonstrated, showing indicators of peak and overall morbidity and mortality and prevailing strains of a new coronavirus infection, depending on the waves of the pandemic. The study evaluated the features of the course of a new coronavirus infection in the Eurasian region using data from the international register "Analysis of the dynamics of comorbid diseases in patients infected with severe acute respiratory syndrome-2 coronavirus”. Modern ideas about the main pathogenetic mechanisms of involvement of the circulatory system, which underlie the development of a severe course, mortality, and lethal outcomes, are outlined. The study also presented the concept of metabolic and hemodynamic insufficiency, which justifies the inability of the desynchronized circulatory system and systems of vascular homeostasis and hemostasis to restore the previous level of functioning after a new coronavirus infection. The possibilities of carrying out differentiated anti-epidemiological measures, including the use of information technologies, aimed at reducing the spread of a new coronavirus infection, were evaluated. The mortality and mortality from a new coronavirus infection in the Armed Forces of the Russian Federation, including the effect of a new coronavirus infection on an increase in the incidence of non-communicable diseases in military personnel of different age groups, were presented. The study also considered issues of the need to introduce a rehabilitation strategy to correct conditions that occur after a new coronavirus infection, reduce the risk of subsequent mortality and lethality, and reduce it in the long term. All rights reserved © Eco-Vector, 2022.

The Effect of FOXP3+Regulatory T Cells on Infectious and Inflammatory Diseases

CD4+CD25+FOXP3+regulatory T cells (Tregs) contribute to the maintenance of immune homeostasis and tolerance in the body. The expression levels and functional stability of FOXP3 control the function and plasticity of Tregs. Tregs critically impact infectious diseases, especially by regulating the threshold of immune responses to pathogenic microorganisms. The functional regulatory mechanism and cell-specific surface markers of Tregs in different tissues and inflammatory microenvironments have been investigated in depth, which can provide novel ideas and strategies for immunotherapies targeting infectious diseases.Copyright © 2021. All rights reserved.

Functioning of the ADAMTS-13/vWF axis and its clinical significance

Advances in biology have allowed us to substantially deepen our knowledge about hemostasis functioning both in health and disease. ADAMTS-13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13) and von Willebrand factor (vWF) are components of the hemostasis system, which physiological interaction holds an important place in maintaining homeostasis. ADAMTS-13 is a metalloproteinase mainly acting to release vWF fragments into the blood plasma, as well as regulating its activity by cleaving ultra-large vWF multimers (UL-vWF) into smaller and less active forms. The study of such factors is of great clinical importance, since a decrease in ADAMTS-13 activity and an increase in vWF level can be predictors of microcirculatory disorders that play an important role in developing multiple organ failure. However, very few and fully contradictory studies devoted to the physiological aspects of the ADAMTS-13/vWF axis functioning in the mother-fetus system are available, therefore requiring to be further investigated.Copyright © 2023 Russian Journal of Forensic Medicine. All rights reserved.

New genetic and epigenetic insights into the chemokine system: the latest discoveries aiding progression toward precision medicine.

Over the past thirty years, the importance of chemokines and their seven-transmembrane G protein-coupled receptors (GPCRs) has been increasingly recognized. Chemokine interactions with receptors trigger signaling pathway activity to form a network fundamental to diverse immune processes, including host homeostasis and responses to disease. Genetic and nongenetic regulation of both the expression and structure of chemokines and receptors conveys chemokine functional heterogeneity. Imbalances and defects in the system contribute to the pathogenesis of a variety of diseases, including cancer, immune and inflammatory diseases, and metabolic and neurological disorders, which render the system a focus of studies aiming to discover therapies and important biomarkers. The integrated view of chemokine biology underpinning divergence and plasticity has provided insights into immune dysfunction in disease states, including, among others, coronavirus disease 2019 (COVID-19). In this review, by reporting the latest advances in chemokine biology and results from analyses of a plethora of sequencing-based datasets, we outline recent advances in the understanding of the genetic variations and nongenetic heterogeneity of chemokines and receptors and provide an updated view of their contribution to the pathophysiological network, focusing on chemokine-mediated inflammation and cancer. Clarification of the molecular basis of dynamic chemokine-receptor interactions will help advance the understanding of chemokine biology to achieve precision medicine application in the clinic.

Plitidepsin Is a Broad-Spectrum Antiviral Shaping the Cell Proteostatic Balance

Background: Different viruses employ similar pathways for replication, revealing key intracellular hotspots to target with host-directed therapies and achieve a broad-spectrum antiviral activity. Plitidepsin is a clinically approved antitumoral agent that blocks the elongation factor eEF1A required for protein translation. This drug counteracts SARS-CoV-2 replication and shows a favorable safety profile in COVID-19 patients. Yet, the precise antiviral mechanism of action of plitidepsin remains unknown. Method(s): Here we used a deep quantitative proteomic analysis to measure the impact of plitidepsin on the proteome of SARS-CoV-2-infected Vero E6 cells. This was complemented with transmission electron microscopy assays, which unraveled the subcellular and morphological changes associated to plitidepsin treatment. In addition, we performed functional in vitro assays to dissect the antiviral activity of plitidepsin against SARS-CoV-2 and other viruses. Result(s): We found that this drug inhibited the synthesis of all SARS-CoV-2 proteins in a dose-dependent manner. These included the R1AB polyproteins, which facilitate the synthesis of non-structural proteins involved in the formation of double membrane vesicles (DMV) required for viral replication. Plitidepsin reduced DMV formation and the morphogenesis of new viruses, having a greater impact on viral than on host proteins. Less than 14% of the cellular proteome was significantly affected by plitidepsin, inducing the up-regulation of key molecules associated with protein biosynthesis, such as the translation initiation factors eIF4A2 and eIF2S3. Therefore, plitidepsin induced a compensatory state that rescued protein translation. This proteostatic response explains how cells preserve the cellular proteome after treatment with a translation inhibitor such as plitidepsin. In addition, it suggests that plitidepsin could inhibit other RNA-dependent and non-integrated DNA viruses, as we confirmed in vitro using Zika virus, Hepatitis C virus replicon and Herpes simplex virus. However, the compensatory proteostasis induced by plitidespin also explains why this drug failed to inhibit the replication of integrated DNA proviruses such as HIV-1. Conclusion(s): Unraveling the mechanism of action of host-directed therapies like plitidepsin is imperative to define the indications and antiviral profile of these compounds. This knowledge will be key to develop broad-spectrum treatments and have them ready to deploy when future pandemic viruses break through.

Nonhuman Primate Model of Long Covid: Immune Insights of Glycometabolic Dysfunctions

Background: A major consequence of COVID-19 is long-term metabolic complications (metabolic PASC or Long COVID) following acute disease resolution leading to hyperglycemia, increased risk of diabetes or defects in glucose metabolism. However, the mechanisms underlying the links between COVID-19 and glycometabolic disruptions remain unclear. Method(s): 15 African green monkeys (AGM;Chlorocebus aethiops) were infected with SARS-CoV-2 (Wuhan stain) and divided into two groups: unvaccinated (n=10) and vaccinated (BNT162b2 (Pfizer) 4-days post infection;n=5). Subgenomic SARS-CoV-2 mRNA (sgRNA) reflecting active replication was quantified in nasal and pharyngeal swabs, and blood chemistry analysis was performed longitudinally up to 18 weeks post-infection. We quantified liver glycogen at necropsy using Periodic acid-Schiff staining. Finally, we longitudinally analyzed 96 plasma proteins using a proximity extension assay (Olink). STRING was used to identify enriched protein networks. Comparisons between the two groups over time were performed using PERMANOVA. Result(s): All animals had detectable sgRNA ( >3.64x106) at day 3, and only two were undetectable at week 5. Post-infection BNT162b2 vaccination partially inhibited the SARS-CoV-2 mediated disruption of glucose levels (P=0.001, Fig. 1A). Liver glycogen levels following necropsy correlated positively with blood glucose levels at week 12 (r=0.74, P =0.003). Histopathological analysis revealed no marked evidence of long-term inflammation or fibrosis of pancreatic islets. Using the plasma proteomic data, we identified a signature of 15 SARS-CoV-2-modulated plasma proteins coinciding with early onset hyperglycemia during acute infection (P=0.001, Fig. 1B). These proteins are enriched for biological processes linked to chemotaxis (FDR=1.38E-06), and viral protein interaction with cytokines (FDR=1.01E-12) (Fig. 1C). Of these, CCL25 and glial cell derived neurotrophic factor (GDNF) remained persistently elevated post-acute infection and correlated with blood glucose levels (r=0.57, P=0.0003;and r=0.64, P<0.0001, respectively, Fig. 1D). Conclusion(s): Our AGM model validates phenotypes of metabolic PASC and offers an opportunity to mechanistically study the manifestations of PASC. Our preliminary data suggest that vaccine-preventable early insults by metabolicregulating immune factors may contribute to long-term dysregulated liver and systemic glucose homeostasis during PASC. These immune factors warrant further investigation for their mechanistic links to PASC. (Figure Presented).

Controversial role of neutrophilic granulocytes in the immunopathogenesis of COVID-19: correlation with imbalance of pro-inflammatory neutrophil-associated cytokines and interferon alpha deficiency.

Neutrophilic granulocytes (NG) are the main drivers of pathological inflammation in COVID-19. Objective. To specify the mechanisms of immunopathogenesis of COVID-19 based on a comparative immunological study of the number and phenotype of CD16+SD62L+CD11b+CD63- and CD16+SD62L+CD11b+CD63+ subsets with an assessment of their effector functions against changing profile of NG-associated cytokines IL-8, IL-18, IL-17A, VEGF-A, IFNalpha, and IFNgamma. Patients and methods. In patients with moderate-to-severe and severe COVID-19, we determined IL-1beta, TNFalpha, IL-6, IL-8, IL-18, IL-17A, VEGF-A, IFNalpha, and IFNgamma (ELISA), the phenotype of CD16+SD62L+CD11b+CD63- and CD16+SD62L+CD11b+CD63+ subsets, NF-kappaB-NG (CYTOMICS FC500), phagocytically active NG (%), neutrophil extracellular traps (NETs), NG in apoptosis, and the activity of NADPH oxidase. Results. In COVID-19 against the background of IFNalpha and IFNgamma production blockade and high levels of NG-associated IL-8, IL-18, IL-17A, VEGF-A, a reduction in the number of mature and functionally active CD16brightSD62LbrightCD11bbrightCD63-NG subsets was revealed, as well as an increase in the number of CD16dimSD62LdimSD11bbrightCD63-NG subsets with an immunosuppressive phenotype and CD16brightSD62LbrightSD11bbrightCD63bright-NG subsets with high cytotoxic activity and ability to form NETs, a decrease in the percentage of phagocytically active NG and an increase in the activity of NADPH oxidase, NETs, and NG in apoptosis. Conclusion. IFNalpha deficiency provokes a hyperergic response of NG-associated cytokines, which leads to the formation of uncontrolled immune inflammation involving NG subsets with an immunosuppressive and cytotoxic phenotype, exacerbating the course of COVID-19. The use of recombinant IFNalpha-2b with antioxidants (Viferon) in the early stages of the disease can help to restore immune homeostasis, normalize the level of NG-associated cytokines, reduce NERTs, and achieve good clinical efficacy.Copyright © 2022, Dynasty Publishing House. All rights reserved.

NAD+ metabolism-based immunoregulation and therapeutic potential.

Nicotinamide adenine dinucleotide (NAD+) is a critical metabolite that acts as a cofactor in energy metabolism, and serves as a cosubstrate for non-redox NAD+-dependent enzymes, including sirtuins, CD38 and poly(ADP-ribose) polymerases. NAD+ metabolism can regulate functionality attributes of innate and adaptive immune cells and contribute to inflammatory responses. Thus, the manipulation of NAD+ bioavailability can reshape the courses of immunological diseases. Here, we review the basics of NAD+ biochemistry and its roles in the immune response, and discuss current challenges and the future translational potential of NAD+ research in the development of therapeutics for inflammatory diseases, such as COVID-19.

Role of GM-CSF in lung balance and disease.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a hematopoietic growth factor originally identified as a stimulus that induces the differentiation of bone marrow progenitor cells into granulocytes and macrophages. GM-CSF is now considered to be a multi-origin and pleiotropic cytokine. GM-CSF receptor signals activate JAK2 and induce nuclear signals through the JAK-STAT, MAPK, PI3K, and other pathways. In addition to promoting the metabolism of pulmonary surfactant and the maturation and differentiation of alveolar macrophages, GM-CSF plays a key role in interstitial lung disease, allergic lung disease, alcoholic lung disease, and pulmonary bacterial, fungal, and viral infections. This article reviews the latest knowledge on the relationship between GM-CSF and lung balance and lung disease, and indicates that there is much more to GM-CSF than its name suggests.

An overview on in vitro and in vivo antiviral activity of lactoferrin: its efficacy against SARS-CoV-2 infection.

Beyond the absolute and indisputable relevance and efficacy of anti-SARS-CoV-2 vaccines, the rapid transmission, the severity of infection, the absence of the protection on immunocompromised patients, the propagation of variants, the onset of infection and/or disease in vaccinated subjects and the lack of availability of worldwide vaccination require additional antiviral treatments. Since 1987, lactoferrin (Lf) is well-known to possess an antiviral activity related to its physico-chemical properties and to its ability to bind to both heparan sulfate proteoglycans (HSPGs) of host cells and/or surface components of viral particles. In the present review, we summarize in vitro and in vivo studies concerning the efficacy of Lf against DNA, RNA, enveloped and non-enveloped viruses. Recent studies have revealed that the in vitro antiviral activity of Lf is also extendable to SARS-CoV-2. In vivo, Lf oral administration in early stage of SARS-CoV-2 infection counteracts COVID-19 pathogenesis. In particular, the effect of Lf on SARS-CoV-2 entry, inflammatory homeostasis, iron dysregulation, iron-proteins synthesis, reactive oxygen formation, oxidative stress, gut-lung axis regulation as well as on RNA negativization, and coagulation/fibrinolysis balance will be critically reviewed. Moreover, the molecular mechanisms underneath, including the Lf binding to HSPGs and spike glycoprotein, will be disclosed and discussed. Taken together, present data not only support the application of the oral administration of Lf alone in asymptomatic COVID-19 patients or as adjuvant of standard of care practice in symptomatic ones but also constitute the basis for enriching the limited literature on Lf effectiveness for COVID-19 treatment.

Microbiota shaping and bioburden monitoring of indoor antimicrobial surfaces

Indoor residents are constantly exposed to dynamic microbiota that have significant health effects. In addition to hand hygiene, cleaning, and disinfection, antimicrobial coatings (AMCs) can prevent the spread of infectious diseases in public areas. The sustainable use of antimicrobial-coated products requires an assessment of their pros and cons for human health and the environment. The toxicity and resistance risks of AMCs have been considered, but large-scale genetic studies on the microbial community compositions and resistomes of AMCs are scarce. The use of an AMC can reduce the total number of microbes on a surface but poses the risk of dysbiosis, microbial imbalance, such as the polarized growth of metallophilic, metal- and antimicrobial-resistant, and other survivor bacteria, and the overall reduction of microbial diversity. Loss of diversity may lead to the enrichment of harmful bacteria and an increased risk of communicable or immunological non-communicable inflammatory diseases (NCDs). In public buildings, such as kindergartens and nursing homes for the elderly, the use of AMCs is likely to increase due to epidemics and pandemics in recent years. Therefore, comprehensive metagenomic research is needed to monitor the effects of AMCs on indoor microbial community compositions and functions. Although the determination of good indoor microbiota and homeostasis is difficult, microbial communities that have health-protective or harmful effects can and should be identified using a metagenomic sequencing approach before the large-scale implementation of AMCs.

EXTRACORPOREAL THERAPY IN CRITICALLY ILL PATIENTS WITH COVID-19: A SINGLE-CENTER EXPERIENCE.

Aim To assess the safety and efficacy of extracorporeal therapy in patients with COVID-19. The study included 27 patients aged 67+/-9.7 [min 38, max 87] years with a laboratory-confirmed SARS-CoV-2 and bilateral polysegmental pneumonia, various concomitant chronic diseases who were admitted to Intensive Care Unit and received extracorporeal therapies. All patients had the mean NEWS score of 6.9+/-2.7 [min 4, max 9] and the mean SOFA score of 8.1+/-3.1 [min 3, max 16] at admission Methods to the ICU. 19 patients (70.4%) had severe lung lesions over 75% according to the chest CT scans. 48 extracorporeal therapies were performed using the Multifiltrate (Fresenius Medical Care, Germany) and Aquarius (Nikkiso Aquarius RCA, Great Britain) medical devices. Indications for extracorporeal therapy initiation included cytokine storm associated with acute respiratory distress syndrome and septic shock. Generally, each patient received at least one extracorporeal therapy. 11 patients underwent 2 to 6 sessions. Isolated plasma separation and hemoperfusion helped to reduce vasopressor / cardiotonic support, slightly improved ventilation parameters, with a significant, but not long-term decrease in the levels of inflammation markers. Combining different modalities of extracorporeal therapy that provide rapid elimination of agents, controlled temperature response and hydration, maintaining Results homeostasis and detoxification, appeared to be most optimal. Extracorporeal therapy did not improve the volume of lung parenchyma or lung parenchyma damage. However, 19 (70.4%) patients who received extracorporeal therapy transitioned from mechanical ventilation to spontaneous breathing, whereas 8 (29.6%) patients had severe lung lesions (over 75%) according to the repeated chest CT scans. The mean length of stay in the ICU among survivors was 9+/-3.5 [min 4, max 22]. The 28-day mortality and in-hospital mortality rate was 25.9% (7). Prolonged extracorporeal therapy in patients with SARS-Cov-2 has demonstrated Conclusion efficacy in relieving organ dysfunctions and shock states, but did not significantly affect the remaining lung parenchyma damage.Copyright © 2022 University of Latvia. All Rights Reserved.

The Role of Microbiota in Gut Inflammation and Sepsis

In healthy individuals, the microbiome and human gut are in homeostasis. Upon dysbiosis, disease and injury, homeostasis is disrupted, which can lead to inflammation and sepsis. In this review, we will focus on how the microbiome interacts with the gut epithelium, underlying vasculature and immune system to maintain homeostasis and how disruption leads to inflammatory bowel disease (IBD), type II diabetes (T2D), novel coronavirus disease-19 (COVID-19) and sepsis. We will discuss antibiotics and the potential for fecal microbiota transplantation (FMT) in sepsis treatment. Finally, we will examine the role of diet and review current experimental models for studying host-microbiome interactions. © 2022 Elsevier Inc. All rights reserved.

Fu-Zheng-Xuan-Fei formula promotes macrophage polarization and Th17/Treg cell homeostasis against the influenza B virus (Victoria strain) infection.

ETHNOPHARMACOLOGICAL RELEVANCE: Fu-Zheng-Xuan-Fei formula (FF) is a prescription that has been clinically used through the basic theory of traditional Chinese medicine (TCM) for treating viral pneumonia. Although FF possesses a prominent clinical therapeutic effect, seldom pharmacological studies have been reported on its anti-influenza B virus (IBV) activity. AIM OF THE STUDY: Influenza is an acute infectious respiratory disease caused by the influenza virus, which has high annual morbidity and mortality worldwide. With a global decline in the COVID-19 control, the infection rate of influenza virus is gradually increasing. Therefore, it is of great importance to develop novel drugs for the effective treatment of influenza virus. Apart from conventional antiviral drugs, TCM has been widely used in the clinical treatment of influenza in China. Therefore, studying the antiviral mechanism of TCM can facilitate the scientific development of TCM. MATERIALS AND METHODS: Madin-Darby canine kidney cells (MDCK) and BALB/c mice were infected with IBV, and FF was added to evaluate the anti-IBV effects of FF both in vitro and in vivo by Western blotting, immunofluorescence, flow cytometry, and pathological assessment. RESULTS: It was found that FF exhibited anti-viral activity against IBV infection both in vivo and in vitro, while inducing macrophage activation and promoting M1 macrophage polarization. In addition, FF effectively regulated the signal transducer and activator of transcription (STAT) signaling pathway-mediated Th17/Treg balance to improve the lung tissue damage caused by IBV infection-induced inflammation. The findings provided the scientific basis for the antiviral mechanism of FF against IBV infection. CONCLUSIONS: This study shows that FF is a potentially effective antiviral drug against IBV infection.