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Pregnant women infected with pathogenic respiratory viruses, such as influenza A viruses (IAV) and coronaviruses, are at higher risk for mortality, hospitalization, preterm birth, and stillbirth. Several factors are likely to contribute to the susceptibility of pregnant individuals to severe lung disease including changes in pulmonary physiology, immune defenses, and effector functions of some immune cells. Pregnancy is also a physiologic state characterized by higher levels of multiple hormones that may impact the effector functions of immune cells, such as progesterone, estrogen, human chorionic gonadotropin, prolactin, and relaxin. Each of these hormones acts to support a tolerogenic immune state of pregnancy, which helps prevent fetal rejection, but may also contribute to an impaired antiviral response. In this review, we address the unique role of adaptive and innate immune cells in the control of pathogenic respiratory viruses and how pregnancy and specific hormones can impact their effector actions. We highlight viruses with sex‐specific differences in infection outcomes and why pregnancy hormones may contribute to fetal protection but aid the virus at the expense of the mother's health. [ABSTRACT FROM AUTHOR]

This study was performed to investigate the tissue-specific effects of clothianidin on Oncorhynchus mykiss by evaluating the biochemical and histological alterations following 21 days of treatment to environmentally relevant concentrations of 3, 15, and 30 µg/L. The emerged behavioral changes in feeding and swimming performance were considered as adaptive responses to avoid the chemical. The toxic effect of pesticide on nervous system and osmoregulation was evidenced with the inhibition of AChE and Na+K+-ATPase. The sustained lipid peroxidation, ranging from muscle (196%) > brain (154%) > gill (140%) > kidney (129%), might be suggested as a mechanism mediating the inhibition of membrane-bound enzymes. Histological evaluation showed clothianidin-induced lesions appearing as necrosis, atrophy, and edema in muscle, hyperplasia, and hypertrophy causing shortening and fusion of the secondary lamellae in gill, vacuolization, and hydropic degeneration in brain, degeneration of tubular epithelium, and existence of melanomacrophage centers in kidney. The pronounced degenerative changes observed in gill indicate the vulnerability of tissue possibly due to its role as first contact and entry point for the pesticide. Consequently, clothianidin exerted its toxic effects by altering normal behavior, causing neurotoxicity and disturbing osmoregulation. Moreover, the imposed stress was responded in a tissue-specific manner and histological lesions become more severe with increasing concentration. The findings clearly reveal the potential threat caused by environmentally relevant concentrations of clothianidin to early life stages of fish. [ABSTRACT FROM AUTHOR]

Simple Summary: This research aimed to define intestinal DCs from myxines to teleosts by using immunohistochemistry with TLR-2, Langerin/CD207, and MHC II. In particular, we analyzed intestinal DCs in several species of fish phylogenetically organized: Eptatretus cirrhatus (myxines), Scyliorhinus canicula (Chondrichthyes), Polypterus senegalus (Osteichthyes, Brachiopterygii), Lepisosteus oculatus (Osteichthyes, Holostei), and Clarias batrachus (Osteichthyes, Teleostei). The findings show that intestinal DCs and DC-like cells are positive to all the antibodies tested, demonstrating the presence of these cells phylogenetically from myxines to teleosts. These results could improve the state-of-the-art on the evolution of the immune system and the importance of sentinel cells in the body's defense. In addition, we demonstrated with immunohistochemistry the presence of MHC II in myxines (Eptatretus cirrhatus) for the first time. Dendritic cells (DCs) are antigen-presenting cells (APCs) that regulate the beginning of adaptive immune responses. The mechanisms of tolerance to antigens moving through the digestive tract are known to be regulated by intestinal DCs. Agnatha and Gnathostoma are descendants of a common ancestor. The Ostracoderms gave rise to Cyclostomes, whereas the Placoderms gave rise to Chondrichthyes. Sarcopterygii and Actinopterygii are two evolutionary lines of bony fishes. Brachiopterygii and Neopterygii descend from the Actinopterygii. From Neopterygii, Holostei and Teleostei evolved. Using immunohistochemistry with TLR-2, Langerin/CD207, and MHC II, this study aimed to characterize intestinal DCs, from myxines to teleosts. The findings reveal that DCs are positive for the antibodies tested, highlighting the presence of DCs and DC-like cells phylogenetically from myxines, for the first time, to teleosts. These findings may aid in improving the level of knowledge about the immune system's evolution and these sentinel cells, which are crucial to the body's defense. [ABSTRACT FROM AUTHOR]

Vitamin K2-7, also known as menaquinone-7 (MK-7) is a form of vitamin K that has health-beneficial effects in osteoporosis, cardiovascular disease, inflammation, cancer, Alzheimer's disease, diabetes and peripheral neuropathy. Compared to vitamin K1 (phylloquinone), K2-7 is absorbed more readily and is more bioavailable. Clinical studies have unequivocally demonstrated the utility of vitamin K2-7 supplementation in ameliorating peripheral neuropathy, reducing bone fracture risk and improving cardiovascular health. We examine how undercarboxylated osteocalcin (ucOC) and matrix Gla protein (ucMGP) are converted to carboxylated forms (cOC and cMGP respectively) by K2-7 acting as a cofactor, thus facilitating the deposition of calcium in bones and preventing vascular calcification. K2-7 is beneficial in managing bone loss because it upregulates osteoprotegerin which is a decoy receptor for RANK ligand (RANKL) thus inhibiting bone resorption. We also review the evidence for the health-beneficial outcomes of K2-7 in diabetes, peripheral neuropathy and Alzheimer's disease. In addition, we discuss the K2-7-mediated suppression of growth in cancer cells via cell-cycle arrest, autophagy and apoptosis. The mechanistic basis for the disease-modulating effects of K2-7 is mediated through various signal transduction pathways such as PI3K/AKT, MAP Kinase, JAK/STAT, NF-κB, etc. Interestingly, K2-7 is also responsible for suppression of proinflammatory mediators such as IL-1α, IL-1β and TNF-α. We elucidate various genes modulated by K2-7 as well as the clinical pharmacometrics of vitamin K2-7 including K2-7-mediated pharmacokinetics/pharmacodynamics (PK/PD). Further, we discuss the current status of clinical trials on K2-7 that shed light on dosing strategies for maximum health benefits. Taken together, this is a synthetic review that delineates the health-beneficial effects of K2-7 in a clinical setting, highlights the molecular basis for these effects, elucidates the clinical pharmacokinetics of K2-7, and underscores the need for K2-7 supplementation in the global diet. [ABSTRACT FROM AUTHOR]

Deltamethrin (Del) is a widely used pyrethroid insecticide and a dangerous material that has brought serious problems to the healthy breeding of aquatic animals. However, the toxicological mechanisms of Del on channel catfish remain unclear. In the present study, we exposed channel catfish to 0, 0.5, and 5 μg/L Del for 6 h, and analyzed the changes in histopathology, trunk kidney transcriptome, and intestinal microbiota composition. The pathological analyses showed that a high concentration of Del damaged the intestine and trunk kidney of channel catfish in the early stage. The transcriptome analysis detected 32 and 1837 differentially expressed genes (DEGs) in channel catfish trunk kidneys after exposure to 0.5 and 5 μg/L Del, respectively. Moreover, the KEGG pathway and GO enrichment analyses showed that the apoptosis signaling pathway was significantly enriched, and apoptosis-related DEGs, including cathepsin L, p53, Bax, and caspase-3, were also detected. These results suggested that apoptosis occurs in the trunk kidney of channel catfish in the early stage of acute exposure to Del. We also detected some DEGs and signaling pathways related to immunity and drug metabolism, indicating that early exposure to Del can lead to immunotoxicity and metabolic disorder of channel catfish, which increases the risk of pathogenic infections and energy metabolism disorders. Additionally, 16S rRNA gene sequencing showed that the composition of the intestinal microbiome significantly changed in channel catfish treated with Del. At the phylum level, the abundance of Firmicutes, Fusobacteria, and Actinobacteria significantly decreased in the early stage of Del exposure. At the genus level, the abundance of Romboutsia, Lactobacillus , and Cetobacterium decreased after Del exposure. Overall, early exposure to Del can lead to tissue damage, metabolic disorder, immunotoxicity, and apoptosis in channel catfish, and affect the composition of its intestinal microbiota. Herein, we clarified the toxic effects of Del on channel catfish in the early stage of exposure and explored why fish under Del stress are more vulnerable to microbial infections and slow growth. [ABSTRACT FROM AUTHOR]

Objective: To determine the frequency of Rh alloantibodies in pregnant women of the Rh-D negative blood group. Study Design: Cross-sectional study. Place and Duration of Study: Armed Forces Institute of Transfusion (AFIT) Rawalpindi, from Jan to Dec 2017. Methodology: The blood samples of pregnant women received for blood grouping, cross matching and antibodies screening were included in the study. The blood was typed for Rh-D along with ABO blood groups by Column Agglutination Technique (CAT), commonly known as the gel card method. Then, the samples included in the study were subjected to antibody screening by three cell antibody screening panel (Dia Cell, a product of Bio-Rad) by Column Agglutination Technique. The samples with positive antibody screening were further processed by 11 cell antibody screening panel (Dia Cell, Bio-Rad) for Rh antibody identification by Column Agglutination Technique, the same as the indirect antiglobulin test (IAT). Results: 453 Rh-D negative pregnant women were screened for alloantibodies during the study period. Rh alloantibodies were present in 55 (12.08%) cases. The most common alloantibody identified was anti-D in 48 (87.3%) samples, followed by anti-C in 6 (10.9%) and anti-E in 1 (1.8%) case. Conclusion: The most prevalent Rh alloantibody identified in Rh-D negative pregnant women was anti-D, while the anti-C and anti-E were less prevalent. However, no case of anti-c and anti-e alloantibody was identified. [ABSTRACT FROM AUTHOR]

Multidrug-resistant Edwardsiella tarda has been reported as the main causative agent for massive fish mortality. The pathogen is well-known for causing hemorrhagic septicemia in fish and has been linked to gastrointestinal infections in humans. Formalin-inactivated Edwardsiella vaccination has previously been found to be ineffective in aquaculture species. Therefore, based on E. tarda's integrated core complete sequenced genomes, the study aimed to design a subunit vaccine based on T and B cell epitopes employing immunoinformatics approach. Initially, the top immunodominant and antigenic epitopes were predicted from the core complete sequenced genomes of the E. tarda genome and designed the vaccine by using linkers and adjuvant. In addition, vaccine 3D structure was predicted followed by refinement, and molecular docking was performed for the analysis of interacting residues between vaccines with TLR5, MHC-I, and MHC-II, respectively. The final vaccine constructs demonstrated strong hydrogen bond interactions. Molecular dynamic simulation of vaccine-TLR5 receptor complex showed a stable structural binding and compactness. Furthermore, E. coli used as a model organism for codon optimization proved optimal GC content and CAI value, which were subsequently cloned in vector pET2+ (a). Overall, the findings of the study imply that the designed epitope vaccine might be a good option for prophylaxis for E. tarda. [ABSTRACT FROM AUTHOR]

Tilapia tilapinevirus, known worldwide as tilapia lake virus (TiLV), is a single-stranded RNA virus that belongs to the Amnoonviridae family. The virus attacks the fish species' external and internal organs, such as the eyes, brain, and liver. Syncytial cells develop in the liver cells of infected fish, which are characterized by widespread hepatocellular necrosis and karyolytic nuclei. It is a highly infectious virus that spreads both horizontally and vertically. Despite these devastating complications, there is still no cure or vaccine for the virus. Therefore, a vaccine based on epitopes developed using immunoinformatics methods was developed against TiLV in fish. The putative polymerase basic 1 (PB1) gene was used to identify immunodominant T- and B-cell epitopes. Three probable epitopes were used to design the vaccine: CTL, HTL, and LBL. Testing of the final vaccine revealed that it was antigenic, non-allergenic, and has improved solubility. Molecular dynamics simulation revealed significant structural compactness and binding stability. Furthermore, the computer-generated immunological simulation indicated that immunization might stimulate real-life immune responses following injection. Overall, the findings of the study imply that the designed epitope vaccine might be a good option for prophylaxis for TiLV. [ABSTRACT FROM AUTHOR]

The pathogenic enterobacterium, Serratia marcescens, is a potential fish pathogen having been isolated in fish culturing environments. However, information on its effects on the physiology of cultured fish species is scarce. This study therefore aimed at ascertaining the physiological status of African catfish (Clarias gariepinus) that has been experimentally challenged with S. marcescens. Healthy juvenile C. gariepinus were experimentally challenged with either 1 × 104 CFU/ml or 5 × 104 CFU/ml inoculums of S. marcescens via oral gavage and the hematological (percentage packed cell volume (PCV), red blood cells (RBC) counts, white blood cells (WBC), counts and differential leucocytes counts) and innate humoral (plasma levels of nitric oxide and respiratory burst) parameters were determined at 4 h, 24 h, 48 h, and 14 days post-challenge periods. The control fish were gavaged with distilled water. The bacterial-challenged fish had significantly higher WBC counts, and increased levels of plasma nitric oxide and respiratory burst while the RBC counts and the PCV decreased significantly in the bacterial-challenged fish compared to control. The response of the fish to bacterial challenge is both inoculum size- and duration-dependent. The incubation of C. gariepinus with 5 × 104 CFU/mL inoculums of S. marcescens elicited more effects in the fish compared to the control or 1 × 104 CFU/mL group. The results of this study showed that infection with S. marcescens has the potential to modulate the immune system of the fish with the inflammatory pathways playing an important role in the defense of the fish against bacterial infection. [ABSTRACT FROM AUTHOR]

In immunology, the discovery of regulatory T (Treg) cells was a major breakthrough. Treg cells play a key role in pregnancy maintenance, in the prevention of autoimmune responses, and in the control of all immune responses, including responses to self cells, cancer, infection, and a transplant. It is currently unclear whether Treg cells are capable of long-term memory of an encounter with an antigen. Although the term "immunological memory" usually means an enhanced ability to protect the body from reinfection, the memory of the suppressive activity of Treg cells helps to avoid the state of generalized immunosuppression that may result from the second activation of the immune system. In this review, we would like to discuss the concept of regulatory memory and in which tissues memory Treg cells can perform their functions. [ABSTRACT FROM AUTHOR]

Simple Summary: Rabbits are animals sensitive to alimentary disturbances and various spoilage agents, mostly during the weaning period. For this reason, the use of natural feed additives has become an area of research in rabbit nutrition, mainly with a focus on prevention. The "in vivo" administration of bacteriocins/enterocins shows an increasing potential in the prevention/treatment of animals' diseases. Therefore, our study focused on the preventive potential of the dipeptide enterocin (Ent) A/P against the methicillin-resistant (MR) Staphylococcus epidermidis SE P3/Tr2a strain in rabbit model, determining its effect on the growth performance, phagocytic activity, secretory (s) IgA, and gut microbial composition of rabbits. Ent A/P increased the weight gain of rabbits and its antibacterial effect showed a tendency to stabilize and improve gut microbiota due to reduction of MR staphylococci, total bacteria, and coliforms. The immune-stimulatory effect of Ent A/P was noted due to increased phagocytic activity. Achieved results showed the great potential of Ent A/P application as a feed additive in rabbit nutrition to improve the health and productivity of animals. The present study investigated the effect of the dipeptide enterocin (Ent) A/P on growth, immune response, and intestinal microbiota in rabbits. Eighty-eight rabbits (aged five weeks, M91 meat line, both sexes) were divided into three experimental groups: E (Ent A/P; 50 µL/animal/day for 14 days; between 0–14 days); S (methicillin-resistant Staphylococcus epidermidis SE P3/Tr2a strain; 500 µL/animal/day for 7 days starting at day 14 to day 21); and E + S (Ent A/P between 0–14 days and SE P3/Tr2a strain between 14–21 days) groups, and the control group (C). The additives were administered in drinking water. Administration of Ent A/P lead to an increase in weight gain, reduction of feed conversion; phagocytic activity was stimulated and gut microbiota were optimized due to reduction of coliforms, total bacterial count, and methicillin-resistant staphylococci. Good health and increased weight gain also showed that methicillin-resistant S. epidermidis SE P3/Tr2a strain did not have any pathogenic effect on rabbits' health status. [ABSTRACT FROM AUTHOR]

Industrialization has resulted in a massive increase in garbage output, which is frequently discharged or stored in waterways like rivers and seas. Due to their toxicity, durability, bioaccumulation, and biomagnification, heavy metals (such as mercury, cadmium, and lead) have been identified as strong biological poisons. Their presence in the aquatic environment has the potential to affect water quality parameters and aquatic life in general. Teleosts' histopathology provides a sensitive indicator of pollutant-induced stress, because their organs have a central role in the transformation of different active chemical compounds in the aquatic environment. In particular, the gills, kidneys, and liver are placed at the center of toxicological studies. The purpose of this study is to examine the morphological changes caused by heavy metals in the kidney and gills of Boops boops, with a focus on melanomacrophages centers (MMCs) and rodlet cells (RCs) as environmental biomarkers, using histological and histochemical stainings (hematoxylin/eosin, Van Gieson trichrome, Periodic Acid Schiff reaction, and Alcian Blue/PAS 2.5), and immunoperoxidase methods. Our findings show an increase of MMCs and RCs linked to higher exposure to heavy metals, confirming the role of these aggregates and cells as reliable biomarkers of potential aquatic environmental changes reflected in fish fauna. The cytological study of RCs and MMCs could be important in gaining a better understanding of the complicated immune systems of teleosts. [ABSTRACT FROM AUTHOR]

Simple Summary: The natural presence of opportunistic pathogens in aquatic rearing systems in alignment with favorable conditions (compromised fish immune status and/or inappropriate rearing conditions) might result in serious acute disease episodes that can develop into chronic immune responses. The present study characterizes molecular, cellular and humoral markers of chronic inflammation in a fish species with high commercial value. The intense recruitment of immune cells to the inflammatory focus 21 days after triggering an immune response illustrates a clear chronic character. The cellular response was also noticed with circulating leukocyte numbers rising in the blood of the inflamed fish. Furthermore, the cellular-mediated respiratory burst peaked at 21 days post-injection, suggesting that phagocytes were still actively fighting the inflammatory agent. Regarding the molecular analysis, certain genes appear to be good markers of a chronic inflammation response due to their importance in pathways with high relevance in chronic inflammation settings. The present study can serve as a baseline to assess long-term immune-related responses in future studies. Stress-inducing husbandry and rearing conditions, bacterial infections or parasitic diseases may all lead to chronic inflammation. The immune response will then channel energy away from growth, reproduction and other important physiological processes, to fuel immune-related metabolic responses. The present study aims to unravel the mechanisms and contribute with new information on the molecular, cellular and humoral parameters of European seabass (Dicentrarchus labrax) undergoing chronic inflammation that can be used as health indicators for application in fish health management. European seabass individuals were intra-peritoneally injected with either Freund's Incomplete Adjuvant (FIA) to induce inflammation or Hanks Balanced Salt Solution (HBSS) to serve as sham. Fish were sampled at 24 h, 7, 14 and 21 days post-injection and blood, plasma and head-kidney were collected. The results found were clear indicators of an inflamed peritoneal cavity and an ongoing systemic immune response that persisted for at least 21 days. Locally, inflammation was characterized by an intense recruitment of immune cells that was still evident 21 days after injection, thus illustrating the chronic character of the immune response. Cellular response was also noticed peripherally with leukocyte numbers rising in the blood of FIA-injected fish. Furthermore, the cellular-mediated respiratory burst peaked at 21 days post-FIA injection, suggesting that phagocytes were still actively fighting the phlogistic agent. Regarding the head-kidney molecular analysis, cxcr4 and il34 appear to be good markers of a chronic inflammation response due to their importance for pathways with high relevance in chronic inflammation settings. In addition, opioid receptor nopr seems to be a good marker of a chronic inflammation response due to its role in detecting noxious stimuli. The present study can serve as a baseline to assess long-term immune-related responses in future studies. For that, more research is nonetheless required to select more responsive and specific molecular markers. [ABSTRACT FROM AUTHOR]

Simple Summary: Teleost fish, the most abundant group of vertebrates, represent an excellent tool to establish possible correlations between the histological organization of their lymphoid organs and their immunological capacities. This approach allows us to analyze embryonic and larval lymphopoiesis, the remarkable organization of the teleost thymus, the role of the kidney as a true equivalent of the lympho-hematopoietic bone marrow of higher vertebrates, the mechanisms of antigen trapping in both ellipsoids and the so-called melano-macrophage centers (MMCs) and their relation with the generation of memory and the lack of germinal centers, and the extended development of the lymphoid tissue associated to mucosae. In the last 50 years information on the fish immune system has increased importantly, particularly that on species of marked commercial interest (i.e., salmonids, cods, catfish, sea breams), that occupy a key position in the vertebrate phylogenetical tree (i.e., Agnatha, Chondrichtyes, lungfish) or represent consolidated experimental models, such as zebrafish or medaka. However, most obtained information was based on genetic sequence analysis with little or no information on the cellular basis of the immune responses. Although jawed fish contain a thymus and lympho-hematopoietic organs equivalents to mammalian bone marrow, few studies have accounted for the presumptive relationships between the organization of these cell microenvironments and the known immune capabilities of the fish immune system. In the current review, we analyze this topic providing information on: (1) The origins of T and B lymphopoiesis in Agnatha and jawed fish; (2) the remarkable organization of the thymus of teleost fish; (3) the occurrence of numerous, apparently unrelated organs housing lympho-hematopoietic progenitors and, presumably, B lymphopoiesis; (4) the existence of fish immunological memory in the absence of germinal centers. [ABSTRACT FROM AUTHOR]

B cells are a heterogeneous cell population with differential ontogeny, anatomical location, and functions. B1 B cells are a distinct subpopulation characterized by their unique capacity of self-renewal, the production of large quantities of IL-10, and the ability to secrete protective, anti-inflammatory natural antibodies (NAbs), presumably upon down-regulation of CD1d expression. Although natural antibodies are thought to be protective, due to their polyreactivity, their participation in certain autoimmune diseases has been suggested. In the context of pregnancy, the role of B1 B cells has been discussed controversially. While in human pregnancies B1 B cells and natural/polyreactive antibodies they produce are involved in the development of preeclampsia, in mice they promote healthy gestation and fetal protection. In this work, we aimed to functionally characterize the splenic B1 B cell population during pregnancy in mice. Functional enrichment analysis using only up-regulated transcripts from a transcriptomic profile performed on total splenic B cells from pregnant compared to non-pregnant mice showed augmented cell cycle and DNA replication pathways. Proliferation studies by flow cytometry showed augmented Ki-67 proliferation marker expression and percentages of B1 B cells. Furthermore, B1 B cells produced higher levels of IL-10 and lower levels of TNF-α leading to an increased IL-10/TNF-α ratio and showing an immunoregulatory phenotype. Finally, we observed lower expression of CD1d on B1 B cells, suggesting a higher capacity to produce NAbs in the context of pregnancy. In summary, our results showed not only an expanded and proliferative splenic B1 B cell population during pregnancy but also the acquisition of immunomodulatory capacities suggesting its critical role in the intricate process of pregnancy tolerance. [ABSTRACT FROM AUTHOR]

Introduction. Interest in the potential role of low-density granulocytes (LDGs) in the development of autoimmune diseases has been renewed recently. Due to their pro-inflammatory action, more and more attention is paid to the role of LDGs, including those expressing the enzyme myeloperoxidase (MPO), in the development of autoimmune hepatitis (AIH). LDGs are actively involved in the formation of neutrophil extracellular traps (NETs). This phenomenon may favour the externalization of the autoantigen and lead to damage to internal organs, including the liver. Aim. The main aim of the study was to assess the diagnostic usefulness of the LDG percentage, including the fraction showing MPO expression as markers of systemic inflammation in AIH. Materials and methods. The study included a group of 25 patients with AIH and 20 healthy volunteers. Mononuclear cells, isolated from peripheral blood, were labelled with monoclonal antibodies conjugated to the appropriate fluorochromes (CD15-FITC, CD14-PE, CD10-PE-Cy5, MPO+) and then analyzed on a Navios Flow Cytometer (Beckman Coulter). Results. Patients with AIH had a higher median percentage of LDG (1.2 vs. 0.1; p = 0.0001) and LDG expressing MPO (0.8 vs. 0.3; p = 0.0017) when compared to healthy volunteers. Moreover, the percentage of LDG was characterised by 100% of sensitivity and 55% of specificity (AUC = 0.84; p < 0.0001), while the percentage of LDG expressing MPO was 92% of sensitivity and 55% of specificity (AUC = 0.78; p = 0.0001) in the detection of AIH. Conclusions. Assessment of inflammatory markers, such as the percentage of LDG and the percentage of LDG expressing MPO, may be helpful in assessing the phenomenon of an increased systemic inflammatory response and in assessing liver fibrosis (LC, Liver cirrhosis), which is inherent in liver decompensation. Taking into account the above arguments, the assessment of the percentage of LDG, including LDG expressing MPO, may turn out to be a useful marker in the diagnosis of AIH. [ABSTRACT FROM AUTHOR]

Due to its wide host range and frequently causing significant mortality, infectious spleen and kidney necrosis virus (ISKNV) has caused huge economic losses on mandarin fish in China. There are no commercial drugs to cure ISKNV, and vaccines are regarded as one of the most effective measures to control virus infection. Because of the weak immunogenicity of antigen protein, subunit vaccines may require multiple booster immunizations, adjuvants or carriers to ensure strong and long‐term protective immunity. In this work, based on MCP (main capsid protein) subunit vaccine, we used single‐walled carbon nanotubes (SWCNTs) as carrier and mannose (M) as targeting factors to construct SWCNTs‐M‐MCP vaccine. After injection immunization, rapid and strong antibody titres were detected in SWCNTs‐M‐MCP groups which were significantly higher than that of MCP groups and SWCNTs‐MCP groups at the same immune doses. The antibody titre of the highest immune group (5 μg SWCNTs‐M‐MCP) reached more than 2.5 times that of the control group at 21 days postvaccination. Similar results were found in enzyme activities and immune‐related genes expression. All enzyme activities and immune‐related genes expression of 5 μg SWCNTs‐M‐MCP group at 21 days postvaccination were significantly higher than those of all dosages MCP groups and SWCNTs‐MCP groups. This study showed that SWCNTs and mannose can significantly improve the immune responses of vaccines and may provide an effective strategy against ISKNV. [ABSTRACT FROM AUTHOR]

Understanding the effects of wildlife diseases on populations requires insight into local environmental conditions, host defence mechanisms, host life‐history trade‐offs, pathogen population dynamics, and their interactions. The survival of Tasmanian devils (Sarcophilus harrisii) is challenged by a novel, fitness limiting pathogen, Tasmanian devil facial tumour disease (DFTD), a clonally transmissible, contagious cancer. In order to understand the devils' capacity to respond to DFTD, it is crucial to gain information on factors influencing the devils' immune system. By using RT‐qPCR, we investigated how DFTD infection in association with intrinsic (sex and age) and environmental (season) factors influences the expression of 10 immune genes in Tasmanian devil blood. Our study showed that the expression of immune genes (both innate and adaptive) differed across seasons, a pattern that was altered when infected with DFTD. The expression of immunogbulins IgE and IgM:IgG showed downregulation in colder months in DFTD infected animals. We also observed strong positive association between the expression of an innate immune gene, CD16, and DFTD infection. Our results demonstrate that sampling across seasons, age groups and environmental conditions are beneficial when deciphering the complex ecoevolutionary interactions of not only conventional host‐parasite systems, but also of host and diseases with high mortality rates, such as transmissible cancers. [ABSTRACT FROM AUTHOR]

Researchers have recently renewed interest in bacteriophages. Being valuable models for the study of eukaryotic viruses, and more importantly, natural killers of bacteria, bacteriophages are being tapped for their potential role in multiple applications. Bacteriophages are also being increasingly sought for bacteriophage therapy due to rising antimicrobial resistance among pathogens. Reports show that there is an increasing trend in therapeutic application of natural bacteriophages, genetically engineered bacteriophages, and bacteriophage-encoded products as antimicrobial agents. In view of these applications, the isolation and characterization of bacteriophages from the environment has caught attention. In this review, various methods for isolation of bacteriophages from environmental sources like water, soil, and air are comprehensively described. The review also draws attention towards a handful on-field bacteriophage isolation techniques and the need for their further rapid development. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is a clinical aggravation of TB symptoms observed among a fraction of HIV coinfected patients shortly after the start of antiretroviral therapy (ART). Of note, TB-IRIS is characterized by exacerbated inflammation and tissue damage that occurs in response to the elevated production of CD4+ T cell-derived IFN-γ. Nevertheless, the possible participation of CD8+ T cells in TB-IRIS development remains unclear. Methods: We performed a comprehensive assessment of the composition of CD8+ T cell memory subsets and their association with circulating inflammation-related molecules in TB-HIV coinfected patients initiating ART. Results: We found that TB-IRIS individuals display higher frequencies of Antigen-experienced CD8+ T cells during the onset of IRIS and that the levels of these cells positively correlate with baseline mycobacterial smear grade. TB-IRIS individuals exhibited higher frequencies of effector memory and lower percentages of naïve CD8+ T cells than their Non-IRIS counterparts. In both TB-IRIS and Non-IRIS patients, ART commencement was associated with fewer significant correlations among memory CD8+ T cells and cells from other immune compartments. Networks analysis revealed distinct patterns of correlation between each memory subset with inflammatory cytokines suggesting different dynamics of CD8+ T cell memory subsets reconstitution. TB-IRIS patients displayed lower levels of memory cells positive for CXCR3 (a chemokine receptor that plays a role in trafficking activated CD8+ T cells to the tissues) than Non-IRIS individuals before and after ART. Furthermore, we found that CXCR3+ naïve CD8+ T cells were inversely associated with the risk of TB-IRIS development. On the other hand, we noticed that the frequencies of CXCR3+ effector CD8+ T cells were positively associated with the probability of TB-IRIS development. Conclusion: Our data suggest that TB-IRIS individuals display a distinct profile of memory CD8+ T cell subsets reconstitution after ART initiation. Moreover, our data point to a differential association between the frequencies of CXCR3+ CD8+ T cells and the risk of TB-IRIS development. Collectively, our findings lend insights into the potential role of memory CD8+ T cells in TB-IRIS pathophysiology. [ABSTRACT FROM AUTHOR]

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Currently, atherosclerosis, characterized by the dysfunction of lipid metabolism and chronic inflammation in the intimal space of the vessel, is considered to be a metabolic disease. As the most abundant innate immune cells in the body, macrophages play a key role in the onset, progression, or regression of atherosclerosis. For example, macrophages exhibit several polarization states in response to microenvironmental stimuli; an increasing proportion of macrophages, polarized toward M2, can suppress inflammation, scavenge cell debris and apoptotic cells, and contribute to tissue repair and fibrosis. Additionally, specific exosomes, generated by macrophages containing certain miRNAs and effective efferocytosis of macrophages, are crucial for atherosclerosis. Therefore, macrophages have emerged as a novel potential target for anti-atherosclerosis therapy. This article reviews the role of macrophages in atherosclerosis from different aspects: origin, phenotype, exosomes, and efferocytosis, and discusses new approaches for the treatment of atherosclerosis., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To ascertain the role of inflammation in the response to ocrelizumab in primary-progressive multiple sclerosis (PPMS). Methods: Multicenter prospective study including 69 patients with PPMS who initiated ocrelizumab treatment, classified according to baseline presence [Gd+, n=16] or absence [Gd-, n=53] of gadolinium-enhancing lesions in brain MRI. Ten Gd+ (62.5%) and 41 Gd- patients (77.4%) showed non-evidence of disease activity (NEDA) defined as no disability progression or new MRI lesions after 1 year of treatment. Blood immune cell subsets were characterized by flow cytometry, serum immunoglobulins by nephelometry, and serum neurofilament light-chains (sNfL) by SIMOA. Statistical analyses were corrected with the Bonferroni formula. Results: More than 60% of patients reached NEDA after a year of treatment, regardless of their baseline characteristics. In Gd+ patients, it associated with a low repopulation rate of inflammatory B cells accompanied by a reduction of sNfL values 6 months after their first ocrelizumab dose. Patients in Gd- group also had low B cell numbers and sNfL values 6 months after initiating treatment, independent of their treatment response. In these patients, NEDA status was associated with a tolerogenic remodeling of the T and innate immune cell compartments, and with a clear increase of serum IgA levels. Conclusion: Baseline inflammation influences which immunological pathways predominate in patients with PPMS. Inflammatory B cells played a pivotal role in the Gd+ group and inflammatory T and innate immune cells in Gd- patients. B cell depletion can modulate both mechanisms. [ABSTRACT FROM AUTHOR]

Background: Natural antibodies (NAb) are antibodies that are present in a healthy individual without requiring previous exposure to an exogenous antigen. Selection for high NAb levels might contribute to improved general disease resistance. Our aim was to analyse the genetic background of NAb based on a divergent selection experiment in poultry, and in particular the effect of a polymorphism in the TLR1A gene. Methods: The study population consisted of a base population from a commercial pure-bred elite white leghorn layer line and seven generations of birds from a High and Low selection line. Birds were selected for total KLH-binding NAb titer (IgTotal). An enzyme-linked immunosorbent assay was performed to determine NAb titers in blood plasma for IgTotal and the antibody isotypes IgM and IgG. NAb titers were available for 10,878 birds. Genotypes for a polymorphism in TLR1A were determined for chickens in generations 5, 6 and 7. The data were analysed using mixed linear animal models. Results: The heritability estimate for IgM was 0.30 and higher than that for IgG and IgTotal (0.12). Maternal environmental effects explained 2 to 3% of the phenotypic variation in NAb. Selection for IgTotal resulted in a genetic difference between the High and Low line of 2.4 titer points (5.1 genetic standard deviation) in generation 7. For IgM, the selection response was asymmetrical and higher in the Low than the High line. The frequency of the TLR1A C allele was 0.45 in the base population and 0.66 and 0.04 in generation 7 of the High and Low line, respectively. The TLR1A polymorphism had large and significant effects on IgTotal and IgM. Estimated genotypic effects suggest full dominance of the TLR1A C allele. Significant TLR1A by generation interactions were detected for IgM and IgTotal. Conclusions: The effect of a polymorphism in the TLR1A gene on IgTotal and IgM NAb was confirmed. Furthermore, we provide experimental verification of changes in allele frequencies at a major gene with dominant gene action on a quantitative trait that is subjected to mass selection. TLR1A by generation interactions indicate sensitivity to environmental factors. [ABSTRACT FROM AUTHOR]

In underdeveloped and developing countries, due to poverty, fermentation is one of the most widely used preservation methods. It not only allows extending the shelf life of food, but also brings other benefits, including inhibiting the growth of pathogenic microorganisms, improving the organoleptic properties and product digestibility, and can be a valuable source of functional microorganisms. Today, there is a great interest in functional strains, which, in addition to typical probiotic strains, can participate in the treatment of numerous diseases, disorders of the digestive system, but also mental diseases, or stimulate our immune system. Hence, fermented foods and beverages are not only a part of the traditional diet, e.g., in Africa but also play a role in the nutrition of people around the world. The fermentation process for some products occurs spontaneously, without the use of well-defined starter cultures, under poorly controlled or uncontrolled conditions. Therefore, while this affordable technology has many advantages, it can also pose a potential health risk. The use of poor-quality ingredients, inadequate hygiene conditions in the manufacturing processes, the lack of standards for safety and hygiene controls lead to the failure food safety systems implementation, especially in low- and middle-income countries or for small-scale products (at household level, in villages and scale cottage industries). This can result in the presence of pathogenic microorganisms or their toxins in the food contributing to cases of illness or even outbreaks. Also, improper processing and storage, as by well as the conditions of sale affect the food safety. Foodborne diseases through the consumption of traditional fermented foods are not reported frequently, but this may be related, among other things, to a low percentage of people entering healthcare care or weaknesses in foodborne disease surveillance systems. In many parts of the world, especially in Africa and Asia, pathogens such as enterotoxigenic and enterohemorrhagic Escherichia coli, Shigella spp., Salmonella spp., enterotoxigenic Staphylococcus aureus, Listeria monocytogenes , and Bacillus cereus have been detected in fermented foods. Therefore, this review, in addition to the positive aspects, presents the potential risk associated with the consumption of this type of products. [ABSTRACT FROM AUTHOR]

Acne vulgaris is a chronic disease characterised by the appearance of eruptions such as whiteheads, blackheads, pustules, papules, and cysts. Among factors that cause acne vulgaris are the abnormal keratinisation of the sebaceous canal, bacterial colonisation (Cutibacterium acnes), increased sebum production, genotypic factors, and hormonal disorders. Treatment is often long and tedious, and can lead to a reduction in quality of life and social isolation. The intestinal microbiota is greatly important in the formation of acne lesions. It is also responsible for the proper immunity of the organism. Acne is a disease that can be related to the condition of the digestive tract and its microbiome. Research shows that the use of probiotics may reduce skin eruptions. The probiotic supplementation and cosmetics markets are very dynamically developing. The use of internal supplementation and probiotic-containing cosmetics gives hope for the improvement of the skin condition of people with acne. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a neurodegenerative disease of the central nervous system (CNS), traditionally considered a chronic autoimmune attack against the insulating myelin sheaths around axons. However, the exact etiology has not been identified and is likely multi-factorial. Recently, evidence has been accumulating that implies that autoimmune processes underlying MS may, in fact, be triggered by pathological processes initiated within the CNS. This review focuses on a relatively unexplored immune cell—the "innate-like" B1 lymphocyte. The B1 cell is a primary-natural-antibody- and anti-inflammatory-cytokine-producing cell present in the healthy brain. It has been recently shown that its frequency and function may differ between MS patients and healthy controls, but its exact involvement in the MS pathogenic process remains obscure. In this review, we propose that this enigmatic cell may play a more prominent role in MS pathology than ever imagined. We aim to shed light on the human B1 cell in health and disease, and how dysregulation in its delicate homeostatic role could impact MS. Furthermore, novel therapeutic avenues to restore B1 cells' beneficial functions will be proposed. [ABSTRACT FROM AUTHOR]

Background: In several mammalian species, acute endometritis driven by the recruitment of polymorphonuclear cells (PMN) occurs in response to semen. These PMNs release DNA to form neutrophil extracellular traps (NETs) in cattle, horse and human, leading to sperm entrapment. While there is no evidence of this phenomenon occurring in donkeys, artificial insemination (AI) with frozen‐thawed semen, which results in very poor pregnancy rates, leads to a large PMN recruitment to the uterus. Objectives: To investigate whether donkey semen can trigger NET release (NETosis) and if excessive NETosis occurs in response to frozen‐thawed semen. Study design: In vitro experiments. Methods: Jenny PMNs were exposed to jackass fresh or frozen‐thawed semen, isolated sperm or seminal plasma (SP), over the course of three experiments. NET formation in response to different treatments was assessed through manual quantification of stained slides. A one‐way analysis of variance (ANOVA), followed by a post hoc Sidak test, was carried out to determine statistical significance. Results: NET release occurred in a semen concentration‐ and incubation‐time‐dependent manner. Surprisingly, frozen‐thawed donkey sperm did not increase NETosis rate in comparison with the control (23 ± 2.5% vs. 31 ± 3.7%; P >.05), whereas fresh semen exposure did (78 ± 5.7% vs. 26 ± 3.2%, P <.01). NETosis increased in the presence of SP, regardless of the presence or absence of sperm, in comparison with the control in both fresh (84 ± 5.2% and 77 ± 5.0% vs. 12 ± 2.7%, respectively; P <.01) and frozen (95 ± 2.2% and 94 ± 2.9% vs. 14 ± 3.8%, respectively; P <.01) samples. Moreover, exposure of PMN to viable and motile sperm, in the absence of SP, did not increase NETosis rates (P >.05). Conclusions: Donkey SP, and not sperm‐intrinsic factors, is able to trigger NETosis in both time‐ and semen concentration‐dependent manner. The physiological relevance of such response against semen in the donkey remains to be elucidated. [ABSTRACT FROM AUTHOR]

Intensive animal farming emits to the environment very high concentrations of bioaerosol, mainly composed of microorganisms, including antibiotics resistant strains, and their derivatives. Poland is a significant producer of poultry and swine in Europe; Ukraine is located in the immediate vicinity of Poland and the EU. Thus, the review focuses on the presence of potentially pathogenic and antimicrobial-resistant zoonotic bacteria and antimicrobial genes in the environment of farms and food of animal origin in Poland and Ukraine. Existing data confirms presence of these bacteria in the food animal origin chain environment in both countries. However, it is difficult to compare the scale of multidrug-resistant bacteria (e.g. MRSA, ESBL) dissemination in Poland and Ukraine with other EU countries due to lack of more extensive studies and large-scale monitoring in these two countries. A series of studies concerning resistance of pathogenic bacteria isolated from livestock environment have been published in Poland but usually on single farms with a very limited number of samples, and without a genotypic drug resistance marking. From Ukraine are available only few reports, but also disturbing. The risk of antibiotic-resistant bacteria transmission does not only concern animal farming, but also other facilities of animal origin food supply chains, especially slaughterhouses. [ABSTRACT FROM AUTHOR]

Viruses are endowed with a great ability to adapt to different environments. It means altering their cellular tropism and crossing host animal species barriers. The basis of their evolutionary success lies in subtle genetic changes through mutations and major genetic changes through recombination and nucleotide substitution. Genetic recombination is one of the primary processes that produce the genetic diversity upon which natural selection acts. RNA viruses have a great potential for genetic variation, rapid evolution and adaptation. Since influenza viruses have segmented genome, the reassortment is among important mechanisms for generation of new hybrid strains and/or subtypes. The modifications of viral RNA genome are frequently dependent on RNA polymerases erroneous action during replication, on the evolutionary pressure, on the novel environment of the host, the immune pressure, or antiviral drugs pressure. Shift to the new host species and virus transmission by insect vectors induced changes due to positive selection of variants with higher fitness for host-virus or vector-virus interactions. This article covers basic aspects of genetic diversity mechanisms of mutation and recombination of selected RNA viruses. The Influenza virus, Denga, Zika, West Nile, Rabies and SARS‑CoV-2 are just among several examples of virus genetic variations, that influence rapid evolution of viral diseases, and make design of reliable vaccine quite difficult. [ABSTRACT FROM AUTHOR]

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Toll-like receptors (TLR) are a group of protein belonging to the family of Pattern Recognition Receptors (PRR) which have the ability to distinguish between an organism's own antigens and foreign ones and to induce immunological response. TLR play a significant part in non-specific immunity but at the same time they are also a vital element linking non-specific response to the specific one. A growing number of data seems to indicate that the non-specific immunity mechanisms affect the development and sustenance of alcohol addiction. Alcohol damages the organism's cells not only directly but also through an increase inintestinal permeability which induces innate immune response of peripheral blood cells. The signaling pathway of Toll-like receptors located on the surface of brain immune cells intensifies the inflammatory reaction and, through modifying gene expression of proinflammatory factors, unnaturally supports it. This overly protracted "sterile inflammatory reaction" positively correlates with alcohol craving affecting also the functioning of the reward system structures and increasing the risk of relapse of alcoholism. Recurrent alcoholic binges sensitize the microglia and cause an escalation in inflammatory reaction which also leads to neurodegeneration. The induction of innate immunity signaling pathways exposes clinical symptoms of alcohol addiction such as increased impulsivity, loss of behavioral control, depressive-anxiety symptoms and cognitive dysfunctions. Traditional methods of treating alcohol addiction have tended to focus predominantly on reducing symptoms which—given the frequency of relapses—seems insufficient. The aim of the present paper is to discuss the role of toll-like receptors as elements of the immunity system which, together with the nervous system, plays a crucial part in the pathogenesis of alcohol addiction. We also wish to present pharmacotherapeutic perspectives targeted at the neuroimmunological mechanisms of alcohol addiction. [ABSTRACT FROM AUTHOR]

Obesity is characterized by low-grade, chronic inflammation, which promotes insulin resistance and diabetes. Obesity can lead to the development and progression of many autoimmune diseases, including inflammatory bowel disease, psoriasis, psoriatic arthritis, rheumatoid arthritis, thyroid autoimmunity, and type 1 diabetes mellitus (T1DM). These diseases result from an alteration of self-tolerance by promoting pro-inflammatory immune response by lowering numbers of regulatory T cells (Tregs), increasing Th1 and Th17 immune responses, and inflammatory cytokine production. Therefore, understanding the immunological changes that lead to this low-grade inflammatory milieu becomes crucial for the development of therapies that suppress the risk of autoimmune diseases and other immunological conditions. Cells generate extracellular vesicles (EVs) to eliminate cellular waste as well as communicating the adjacent and distant cells through exchanging the components (genetic material [DNA or RNA], lipids, and proteins) between them. Immune cells and adipocytes from individuals with obesity and a high basal metabolic index (BMI) produce also release exosomes (EXOs) and microvesicles (MVs), which are collectively called EVs. These EVs play a crucial role in the development of autoimmune diseases. The current review discusses the immunological dysregulation that leads to inflammation, inflammatory diseases associated with obesity, and the role played by EXOs and MVs in the induction and progression of this devastating conditi8on. [ABSTRACT FROM AUTHOR]

The gastrointestinal immune system plays an important role in immune homeostasis regulation. It regulates the symbiotic host-microbiome interactions by training and developing the host's innate and adaptive immunity. This interaction plays a vital role in host defence mechanisms and at the same time, balancing the endogenous perturbations of the host immune homeostasis. The fish gastrointestinal immune system is armed with intricate diffused gut-associated lymphoid tissues (GALTs) that establish tolerance toward the enormous commensal gut microbiome while preserving immune responses against the intrusion of enteric pathogens. A comprehensive understanding of the intestinal immune system is a prerequisite for developing an oral vaccine and immunostimulants in aquaculture, particularly in cultured fish species. In this review, we outline the remarkable features of gut immunity and the essential components of gut-associated lymphoid tissue. The mechanistic principles underlying the antigen absorption and uptake through the intestinal epithelial, and the subsequent immune activation through a series of molecular events are reviewed. The emphasis is on the significance of gut immunity in oral administration of immunoprophylactics, and the different potential adjuvants that circumvent intestinal immune tolerance. Comprehension of the intestinal immune system is pivotal for developing effective fish vaccines that can be delivered orally, which is less labour-intensive and could improve fish health and facilitate disease management in the aquaculture industry. [ABSTRACT FROM AUTHOR]

Arginine deimination (citrullination) is a post-translational modification catalyzed by a family of peptidyl arginine deiminase (PAD) enzymes. Cell-based functional studies and animal models have manifested the key role of PADs in various cardiovascular diseases (CVDs). This review summarizes the past 10 years of knowledge on the role of PADs in CVD pathogenesis. It focuses on the PAD functions and diverse citrullinated proteins in cardiovascular conditions like deep vein thrombosis, ischemia/reperfusion, and atherosclerosis. Identification of PAD isoforms and citrullinated targets are essential for directing diagnosis and clinical intervention. Finally, anti-citrullinated protein antibodies (ACPAs) are addressed as an independent risk factor for cardiovascular events. PAD is an unique family of enzymes that permanently converts amino acid arginine to amino acid citrulline in protein. Overexpression or increased activity of PAD has been observed in various CVDs with acute and chronic inflammation as the background. Importantly, far beyond being simply involved in forming neutrophil extracellular traps (NETs), accumulating evidence indicated PAD activation as a trigger for numerous processes, such as transcriptional regulation, endothelial dysfunction, and thrombus formation. In summary, the findings so far have testified the important role of deimination in cardiovascular biology, while more basic and translational studies are essential for further exploration. [ABSTRACT FROM AUTHOR]

In recent years, the increase in awareness of antimicrobial resistance together with the societal demand of healthier meat products have driven attention to health-related traits in livestock production. Previous studies have reported medium to high heritabilities for these traits and described genomic regions associated with them. Despite its genetic component, health- and immunity-related traits are complex and its study by association analysis with genomic markers may be missing some information. To analyse multiple phenotypes and gene-by-gene interactions, systems biology approaches, such as the association weight matrix (AWM), allows combining genome wide association study results with network inference algorithms. The present study aimed to identify gene networks, key regulators and candidate genes associated to immunocompetence in pigs by integrating multiple health-related traits, enriched for innate immune phenotypes, using the AWM approach. The co-association network analysis unveiled a network comprised of 3,636 nodes (genes) and 451,407 edges (interactions), including a total of 246 regulators. From these, five genes (ARNT2 , BRMS1L , MED12L , SUPT3H and TRIM25) were selected as key regulators as they were associated with the maximum number of genes with the minimum overlapping (1,827 genes in total). The five regulators were involved in pathways related to immunity such as lymphocyte differentiation and activation, platelet activation and degranulation, megakaryocyte differentiation, FcγR-mediated phagocytosis and response to nitric oxide, among others, but also in immunometabolism. Furthermore, we identified genes co-associated with the key regulators previously reported as candidate genes (e.g., ANGPT1, CD4, CD36, DOCK1 , PDE4B, PRKCE, PTPRC and SH2B3) for immunity traits in humans and pigs, but also new candidate ones (e.g., ACSL3 , CXADR , HBB , MMP12 , PTPN6 , WLS) that were not previously described. The co-association analysis revealed new regulators associated with health-related traits in pigs. This approach also identified gene-by-gene interactions and candidate genes involved in pathways related to cell fate and metabolic and immune functions. Our results shed new light in the regulatory mechanisms involved in pig immunity and reinforce the use of the pig as biomedical model. [ABSTRACT FROM AUTHOR]

Infectious diseases represent one of the largest medical challenges worldwide. Bacterial infections, in particular, remain a pertinent health challenge and burden. Moreover, such infections increase over time due to the continuous use of various antibiotics without medical need, thus leading to several side effects and bacterial resistance. Our innate immune system represents our first line of defense against any foreign pathogens. This system comprises the innate lymphoid cells (ILCs), including natural killer (NK) cells that are critical players in establishing homeostasis and immunity against infections. ILCs are a group of functionally heterogenous but potent innate immune effector cells that constitute tissue-resident sentinels against intracellular and extracellular bacterial infections. Being a nascent subset of innate lymphocytes, their role in bacterial infections is not clearly understood. Furthermore, these pathogens have developed methods to evade the host immune system, and hence permit infection spread and tissue damage. In this review, we highlight the role of the different ILC populations in various bacterial infections and the possible ways of immune evasion. Additionally, potential immunotherapies to manipulate ILC responses will be briefly discussed. [ABSTRACT FROM AUTHOR]

Aims: The relationship between the innate immune system that creates the polysaccharide antibody response and COVID‐19 is not fully understood. In this study, it was aimed to determine the predictive values of isohaemagglutinins in COVID‐19 severity/mortality. Methods: Approximately 15 440 patients diagnosed with COVID‐19 were examined, and a total of 286 patients with anti‐B and anti‐A1 IgM isohaemagglutinins test results were randomly enrolled in the study. These patients were stratified into two groups according to anti‐A1 (n: 138 blood type B or O) and anti‐B (n: 148 blood type A) IgM isohaemagglutinins. Anti‐A1 or/and anti‐B IgM, biochemical parameters, symptoms, chronic diseases, hospitalisation status, intubation status, admission to intensive care unit (ICU) and exitus status were recorded and evaluated for all patients. Results: Anti‐A1 IgM and anti‐B IgM were significantly lower in ICU patients (7.5 ± 9.9 vs 18.0 ± 20.4 and 5.5 ± 6.3 vs 19.3 ± 33.6 titres, respectively; P <.01) and in exitus patients (3.8 ± 3.6 vs 16.7 ± 18.7 and 3.5 ± 4.7 vs 16.9 ± 29.6 titres respectively; P <.01). In the ROC analysis performed to differentiate between exitus and discharge within groups, the sensitivity of anti‐B IgM and anti‐A1 IgM at cut‐off ≤4 was 88.9% and 79.6%, specificity 66.0% and 73.4%, and AUC 0.831 and 0.861, respectively (P <.01). Anti‐A1 IgM decreased the mortality risk 0.811 times per unit while anti‐B IgM decreased 0.717 times (P <.01). Conclusion: Anti‐B and anti‐A1 isohaemagglutinins, which are an expression of the innate immune system, can be used to predict the severity and mortality of COVID‐19 disease. [ABSTRACT FROM AUTHOR]

Background: Lung adenocarcinoma (LUAD) is the most prevalent non-small cell lung cancer (NSCLC). Patients with LUAD have a poor 5-year survival rate. The use of immune checkpoint inhibitors (ICIs) for the treatment of LUAD has been on the rise in the past decade. This study explored the prognostic role of butyrophilin-like 9 (BTNL9) in LUAD. Methods: Gene expression profile of buytrophilins (BTNs) was determined using the GEPIA database. The effect of BTNL9 on the survival of LUAD patients was assessed using Kaplan-Meier plotter and OncoLnc. Correlation between BTNL9 expression and tumor-infiltrating immune cells (TILs) was explored using TIMER and GEPIA databases. Further, the relationship between BTNL9 expression and drug response was evaluated using CARE. Besides, construction and evaluation of nomogram based on BTNL9 expression and TNM stage. Results: BTNL9 expression was downregulated in LUAD and was associated with a poor probability of 1, 3, 5-years overall survival (OS). In addition, BTNL9 expression was regulated at epigenetic and post-transcriptional modification levels. Moreover, BTNL9 expression was significantly positively correlated with ImmuneScore and ESTIMATEScore. Furthermore, BTNL9 expression was positively associated with infiltration levels of B cells, CD4+ T cells, and macrophages. Kaplan-Meier analysis showed that BTNL9 expression in B cells and dendritic cells (DCs) was significantly associated with OS. BTNL9 expression was significantly positively correlated with CARE scores. Conclusions: These findings show that BTNL9 is a potential prognostic biomarker for LUAD. Low BTNL9 expression levels associated with low infiltration levels of naïve B cells, and DCs in the tumor microenvironment are unfavorable for OS in LUAD patients. [ABSTRACT FROM AUTHOR]

Epidermal mucus is an important barrier and regulating mediator in fish. MicroRNAs (miRNAs) are proved to be involved in various biological processes, also as promising biomarkers for disease diagnosis. Vibrio harveyi has long been a noticeable bacterial pathogen in Cynoglossus semilaevis aquaculture. To find the evidence whether there are indicating miRNAs in mucus and whether the miRNAs are related to infections caused by V. harveyi, miRNA profiles of mucus from V. harveyi infected fish and healthy controls were screened by small RNA sequencing and verified by quantitative real-time PCR. This is the first report about miRNA profiling of flatfish mucus, aiming at illustrating the pathogenesis of V. harveyi caused infection and developing disease-related biomarkers. The results revealed significant differences in expression levels of some miRNAs between infected fish and healthy ones. Three hundred differentially expressed miRNAs were obtained after filtering through FC > 2 or FC < 0.5 and most of the differential miRNAs were downregulated. After verification through qRT-PCR, four unique miRNAs, dre-miR-451, dre-miR-184, dre-miR-205-5p > ssa-miR-205b-5p, and dre-miR-181a-5p > ssa-miR-181a-5p, were identified as V. harveyi infection-related signatures, consistent with sequencing trend. The expression levels of these four miRNAs in the infected fish were all significantly lower than controls. These miRNAs in mucus could be used to differentiate diseased and healthy fish in a non-invasive way with practical value for large-scale disease screening. They also provided new insights into the mechanism underlying the bacterial infections in fish. [ABSTRACT FROM AUTHOR]

The Nuuk harbor is the largest industrial port in Greenland. It is polluted by a number of contaminants including tributyltin (TBT), polychlorinated biphenyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs). Here we analyzed melanomacrophage center (MMC) responses in the spleen and kidney of shorthorn sculpins (Myoxocephalus scorpius) from the harbor and three reference sites in Nuuk, West Greenland. The number and area of splenic MMCs in fish from the most polluted station were significantly lower than those from the less polluted stations (p < 0.01). This suggests that the immune response differed between the fish from the contaminated site and those from the reference sites. This indicates that splenic MMCs of shorthorn sculpins could have a biomarker potential for pollutant exposure. This was, however, not the case for renal MMCs. In addition, this study showed that there were effects of body size on the splenic and renal MMC responses. Therefore, in future studies, body size of shorthorn sculpins needs to be considered when investigating splenic and renal MMC responses. [ABSTRACT FROM AUTHOR]

Pregnancy loss is a common obstetric problem. Significant causes of miscarriage include genetic and epigenetic disorders of the embryo, immunological and endocrine factors, uterine malformations, improper embryo selection, and lifestyle. Perhaps a hitherto underappreciated cause of miscarriage may be an abnormal microbiota composition of the female reproductive system. Lactobacillus spp. is the most common bacteria within the reproductive tract. However, the protective role of Lactobacilli in the vagina has been well described in the literature, while it is still unknown what function Lactobacilli may have in the uterus. Moreover, new research shows that Lactobacillus spp. can have a role in miscarriage. However, both molecular and immunological mechanisms of host-Lactobacillus spp. interactions are not fully understood. Understanding these relationships will help address the importance and extent of the protective role of Lactobacillus spp. in miscarriage. [ABSTRACT FROM AUTHOR]

Purpose: We set out to explore the prognostic value of circulating lymphocyte subsets in patients with nasopharyngeal carcinoma (NPC) before treatment and to investigate changes in lymphocyte subsets resulting from chemoradiotherapy. Patients and Methods: This retrospective study included 677 patients with non-metastatic NPC. The cutoff value of lymphocyte subsets was determined by the receiver operating characteristic curve (ROC), and the prognostic significance of lymphocyte subsets was evaluated by the Log rank test and Cox proportional hazards model. The endpoints were overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRFS) and distant metastasis-free survival (DMFS). Differences in lymphocyte subsets before and after chemoradiotherapy were analyzed by Wilcoxon signed rank test. Results: NPC patients with high levels of CD19+ B cells (> 9.55%) had better 5-year OS (90.4% VS 76.8%, P < 0.001), 5-year PFS (85.3% VS 71.6%, P < 0.001) and 5-year DMFS (94% VS 86.8%, P = 0.002) than patients with low levels of CD19+ B cells. Patients with high levels of CD4+ T cells (> 37.05%) had better 5-year PFS (83% VS 74.2%, P = 0.015) and better 5-year DMFS (95.8% VS 86.7%, P < 0.001) than those with low levels of CD4+ T cells. Multivariate analyses indicated that CD19+ B cell was an independent prognostic factor for OS, PFS and DMFS in NPC. And CD4+ T cell was an independent prognostic factor for PFS and DMFS. Within 1 month after chemoradiotherapy, the percentages of CD4+ T cells, CD19+ B cells, and the CD4/CD8 ratio decreased significantly, while the percentages of CD8+ T cells increased significantly. Conclusion: NPC patients with low levels of CD19+ B cells or CD4+ T cells before treatment have a poor prognosis. In addition, chemoradiotherapy may reduce the body's immune function in NPC patients. [ABSTRACT FROM AUTHOR]

The relevance of gut microbiota in a number of physiological and metabolic processes is undisputed. They have an extremely important role in the prevention and treatment of many lifestyle diseases. Modern man suffers from its constant decomposition. Measures to modulate and stabilise the intestinal balance include dietary supplements containing probiotic strains. The aim of the study was to identify attitudes towards probiotic supplements. The study included 234 respondents of varying gender, age, education, frequency of probiotic consumption and self-assessed knowledge of probiotics. A diagnostic survey method was used. Attitudes were identified using a 5-degree Likert scale. The majority of respondents (64%) declared a positive attitude, the remainder were neutral. No negative attitudes were declared. Factors significantly affecting attitude intensity included frequency of probiotic consumption (p < 0.001), gender (p < 0.025) and declared knowledge (p < 0.04). The use of positive attitudes should be considered in health promotion and management. [ABSTRACT FROM AUTHOR]

Bioactive peptides are short peptide fragments formed by amino acids joined by peptide bonds, can employ health enhancing effects in addition to main nutrition effect. In the native proteins generally these peptides are inactive; they can release by proteolysis to attain their bioactivity. Pulse derived bioactive peptides are isolated from proteolytic enzyme digestion, fermentation, and food processing. Bioactive peptide play important role in human health by affecting the metabolic system, and exhibit a antihypertensive, antioxidative, antcancerous, immunomodulatory, antidiabetic and antimicrobial activity. Bioactivity of pulse derived protein hydrolysates/peptides depends on the amino acid composition, sequence and length. Due to their health promoting bioactive peptides has encouraged the researcher community and the pharmaceutical industry to investigating whether the novel pulse derived bioactive peptide can act as nutraceuticals. [ABSTRACT FROM AUTHOR]

Burkholderia pseudomallei (B. pseudomallei) causes melioidosis, a potentially fatal disease for which no licensed vaccine is available thus far. The host-pathogen interactions in B. pseudomallei infection largely remain the tip of the iceberg. The pathological manifestations are protean ranging from acute to chronic involving one or more visceral organs leading to septic shock, especially in individuals with underlying conditions similar to COVID-19. Pathogenesis is attributed to the intracellular ability of the bacterium to 'step into' the host cell's cytoplasm from the endocytotic vacuole, where it appears to polymerize actin filaments to spread across cells in the closer vicinity. B. pseudomallei effectively evades the host's surveillance armory to remain latent for prolonged duration also causing relapses despite antimicrobial therapy. Therefore, eradication of intracellular B. pseudomallei is highly dependent on robust cellular immune responses. However, it remains ambiguous why certain individuals in endemic areas experience asymptomatic seroconversion, whereas others succumb to sepsis-associated sequelae. Here, we propose key insights on how the host's surveillance radars get commandeered by B. pseudomallei. [ABSTRACT FROM AUTHOR]