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Simple Summary: Biomarkers are molecules found in the body that can indicate current physiological functioning and are frequently used to monitor health and diagnose disease. These biomarkers, such as hormones and immune markers, can provide valuable information on the health and welfare of animals. Knowledge on the normal levels of these biomarkers in various species is a crucial step for monitoring health and understanding disease. In this paper, we report assays and value ranges of biomarkers rarely measured in western lowland gorillas in human care. We also compare concentrations of each biomarker between clinical and non-clinical samples. The levels of the two immune biomarkers were higher in clinical samples, but the levels of the neuroendocrine biomarker were not significantly different between clinical and non-clinical samples. These data contribute toward eventually establishing reference ranges for these biomarkers and help improve our understanding of health and welfare in zoo-housed animals. Physiological data can provide valuable information about the health and welfare of animals. Unfortunately, few validated assays and a lack of information on species-typical levels of circulating biomarkers for wildlife make the measurement, interpretation, and practical application of such data difficult. We validated commercially available kits and calculated reference intervals (herein called "value ranges") for dehydroepiandrosterone-sulfate (DHEA-S), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) in a sample of zoo-housed western lowland gorillas due to the roles these biomarkers play in stress and immune responses. For each biomarker, we present species-specific value ranges for a sample of gorillas in human care (n = 57). DHEA-S did not vary significantly by sex or age, while IL-6 was higher in males and older gorillas and TNF-α was higher in females but not associated with age. We also compared non-clinical with clinical samples (n = 21) to explore whether these biomarkers reflect changes in health status. There was no significant difference between clinical and non-clinical samples for DHEA-S, but both IL-6 and TNF-α were significantly higher in gorillas showing clinical symptoms or prior to death. Additional work is needed to improve our understanding of normal versus clinical variation in these biomarkers, and we encourage continued efforts to identify and validate additional biomarkers that can be used to inform assessments of health and welfare in wildlife. [ABSTRACT FROM AUTHOR]

Summary: In the 2 years since the COVID‐19 pandemic was officially declared, science has made considerable strides in understanding the disease's pathophysiology, pharmacological treatments, immune response, and vaccination, but there is still much room for further advances, especially in comprehending its relationship with obesity. Science has not yet described the mechanisms that explain how obesity is directly associated with a poor prognosis. This paper gathers all published studies over the past 2 years that have described immune response, obesity, and COVID‐19, a historical and chronological record for researchers and the general public alike. In summary, these studies describe how the cytokine/adipokine levels and inflammatory markers, such as the C‐reactive protein, are associated with a higher body mass index in COVID‐19‐positive patients, suggesting that the inflammatory background and immune dysregulation in individuals with obesity may be expressed in the results and that adiposity may influence the immune response. The timeline presented here is a compilation of the results of 2 years of scientific inquiry, describing how the science has progressed, the principal findings, and the challenges ahead regarding SARS‐CoV‐2, COVID‐19, and emerging variants, especially in patients with obesity. [ABSTRACT FROM AUTHOR]

The immune response plays a crucial role in preventing diseases, such as infections. There are two types of immune responses, specific and innate immunity, each of which consists of two components: cellular immunity and humoral immunity. Dysfunction in any immune system component increases the risk of developing certain diseases. Systemic lupus erythematosus (SLE), an autoimmune disease in the human body, develops an immune response against its own components. In these patients, due to underlying immune system disorders and receipt of immunosuppressive drugs, the susceptibility to infections is higher than in the general population and is the single largest cause of mortality in this group. COVID-19 infection, which first appeared in late 2019, has caused several concerns in patients with SLE. However, there is no strong proof of additional risk of developing COVID-19 in patients with SLE, and in some cases, studies have shown less severity of the disease in these individuals. This review paper discusses the immune disorders in SLE and COVID-19. [ABSTRACT FROM AUTHOR]

The circadian clock of vertebrates regulates many biological processes, including the immune system. This paper investigated whether responsiveness to poly (I:C), a synthetic analog of double-stranded RNA used as an immunostimulant, exhibits day/night differences in zebrafish. Fish were intraperitoneally (IP) injected with either phosphate-buffered saline (PBS) or poly (I:C) at two different time points: "Zeitgeber Time" (ZT) 4 (day) and ZT16 (night). Then, 6 h later, fish were euthanized, and tissue samples (skin, liver and kidney) were collected. A control group (intact fish) was also sampled at the same time points. The effect of poly (I:C) on the expression of antioxidant and immune genes was time-of-day-dependent, and the response was stronger following poly (I:C) administration in the day than at night. Time-dependent differences were observed for some genes in the PBS and control groups. However, these differences were tissue-specific. In liver, almost all the genes were affected by time of day. In kidney, poly (I:C) affected the expression of all the gene markers regardless of administration time. These findings highlight the importance of considering the time to administer poly (I:C) when evaluating the fish immune response. [ABSTRACT FROM AUTHOR]

In host-parasite coevolution, the parasite is selected to increase its infectivity while host is selected to resist the parasite infection. It is widely held that parasite-mediated sexual selection can further amplify the selective pressure on the host to overcome parasite infection. In this paper we focus on certain types of parasites, those that can impair the activity of the host immune function to prevent signs of sickness. We show that the effect of sexual selection can actually reduce the selective pressure on the host immune response to adapt to the parasite infection. We design a simple mathematical model for a population of sexually reproducing organism in which individuals are choosy, preferring traits that are correlated negatively with immune system activity. We introduce to this population a parasite that can suppress activation of the host's immune response. Our results show that even though the host immune system is likely to ultimately evolve and adapt to the parasite infection, when sexual selection is part of this process, it can slow down this evolution on the host and give the parasite more time to get established. [ABSTRACT FROM AUTHOR]

Background: Some diet additives have become alternatives to achieve higher yields within the productively sustainable, organic, and ecological margins. Hence, nutrients and microorganisms can be added to the diet for fish immunity improvements, by using the nutrients in the feed, which lead to a positive animal performance. Accordingly, the aim of this paper was to gather information related to the utilization of additives as immunostimulant in tilapia (Oreochromis ssp.), and their physiological performance in the body. Development: Many of these immunostimulants are microorganisms or habitual nutrients in the diet, such as polysaccharides, proteins or lipids, which at high concentrations are capable of creating a stimulating effect, speeding disease resistance through specific or unspecific mechanisms of immunological response, thus becoming primary prophylactic agents. Conclusions: The use of additives as immunostimulants helps prevent the occurrence of common diseases in tilapia culture, by modulating the intestinal system in the different species of genus Oreochromis, thus enhancing the unspecific immune response, and, in turn, some processes like individual growth, feeding efficiency, and stress tolerance can be favored. [ABSTRACT FROM AUTHOR]

Evidence of the effectiveness of B-cell-depleting monoclonal antibodies (mAbs) in multiple sclerosis (MS) prompted a partial revisitation of the pathogenetic paradigm of the disease, which was, so far, considered a T-cell-mediated autoimmune disorder. Mechanisms underlying the efficacy of B-cell-depleting mAbs in MS are still unknown. However, they likely involve the impairment of pleiotropic B-cell functions different from antibody secretion, such as their role as antigen-presenting cells during both the primary immune response in the periphery and the secondary response within the central nervous system (CNS). A potential impact of B-cell-depleting mAbs on inflammation compartmentalised within the CNS was also suggested, but little is known about the mechanism underlying this latter phenomenon as no definite evidence was provided so far on the ability of mAbs to cross the blood–brain barrier and reliable biomarkers of compartmentalised inflammation are lacking. The present paper briefly summarises the immunopathogenesis of MS with a focus on onset of autoimmunity and compartmentalisation of the immune response; mechanisms mediating B-cell depletion and underlying the effectiveness of B-cell-depleting mAbs are also discussed. [ABSTRACT FROM AUTHOR]

Our present study investigates the effects of Illicium verum enriched diet on growth performance, immune response and disease resistance in Catla catla fingerlings against Aeromonas hydrophila. Experimental groups, i.e., infected C. catla were fed with 5 g/kg, 10 g/kg and 15 g/kg of I. verum diet for a period of 30 days showed a significant increase in their final body weight (FBW) over control. There was a significant increase (p < 0.05) in total weight gain (TWG), specific growth rate (SGR), feed conversion rate (FCR), protein efficiency ratio (PER), condition factor (CF) and survival rate (SR) in 10 g/kg and 15 g/kg groups compared to control; also from 31 to 60 days these groups showed an enhanced (p < 0.05) complement activity, phagocytic activity, respiratory burst activity and lysosome activity. The experimental group fed with 10 g/kg of I. verum diet showed the least cumulative mortality rate (5%) compared to 5 g/kg (30%) and 15 g/kg (15%) experimental groups and in control (10%) and negative control (75%). Our present study highlights that challenged fish fed with the mid dosage of 10 g/kg showed a significant increase in overall growth performance, non susceptibility to diseases and tolerance against A. hydrophila in C. catla compared to other experimental groups including the group given with high dosage of 15 g/kg. Thus our results suggest 10 g/kg as the optimal dosage of I. verum that can be used to enrich the fish diet for a better performance and effective immunostimulation in commercially important C. catla for its sustainable culture and is reported for the first time. • First paper to report on antibacterial activity of Illicium verum in Catla catla against Aeromonas hydrophila. • Findings establish that I.verum as a potential immunostimulant candidate for a sustainable C. catla cultivation. • Throws light on the herbal property of I.verum that promotes growth performance and survival rate. • This study suggests an optimal dosage of I.verum enriched diet for sustainable cultivation of C.catla and advises that a high dosage of I.verum does not have a positive effect on the experimental groups. • Reports a very low mortality rate in experimental groups challenged with A.hydrophila. [ABSTRACT FROM AUTHOR]

Recent studies have demonstrated that immune impairment is an essential factor in viral infection for disease development and treatment. In this paper, we formulate an age-structured viral infection model with a nonmonotonic immune response and perform dynamical analysis to explore the effects of both immune impairment and virus control. The basic infection reproduction number is derived for a general viral production rate, which determines the global stability of the infection-free equilibrium. For the immune intensity, we get two important thresholds, the post-treatment control threshold and the elite control threshold. The interval between the two thresholds is a bistable interval, where there are two immune-present infected equilibria. When the immune intensity is greater than the elite control threshold, only one immune-present infected equilibrium exists and it is stable. By assuming the death rate and virus production rate of infected cells to be constants, with the immune intensity as a bifurcation parameter, the system exhibits saddle-node bifurcation, transcritical bifurcation, and backward/forward bifurcation. [ABSTRACT FROM AUTHOR]

Gut microbiota, a collection of microorganisms that live within gastrointestinal tract, provides crucial signaling metabolites for the physiological of hosts. In healthy state, gut microbiota metabolites are helpful for maintaining the basic functions of hosts, whereas disturbed production of these metabolites can lead to numerous diseases such as metabolic diseases, cardiovascular diseases, gastrointestinal diseases, neurodegenerative diseases, and cancer. Although there are many reviews about the specific mechanisms of gut microbiota metabolites on specific diseases, there is no comprehensive summarization of the functions of these metabolites. In this Opinion, we discuss the knowledge of gut microbiota metabolites including the types of gut microbiota metabolites and their ways acting on targets. In addition, we summarize their physiological and pathologic functions in health and diseases, such as shaping the composition of gut microbiota and acting as nutrition. This paper can be helpful for understanding the roles of gut microbiota metabolites and thus provide guidance for developing suitable therapeutic strategies to combat microbial-driven diseases and improve health. [ABSTRACT FROM AUTHOR]

• E-MPBs shows sustained cellular uptake by microglia. • E-MPBs exhibits anti-ROS and anti-inflammation properties against M1 microglia. • E-MPBs develops a novel nanoplatform for SCI. Developing biomimetic nanoparticles without off-target side-effects remains a major challenge in spinal cord injury (SCI) immunotherapy. In this paper, we have conducted a drug carrier which is biocompatible macrophages-exocytosed exosome-biomimetic manganese (Mn)-iron prussian blue analogues (MPBs) for SCI immunotherapy. Exosome-sheathed MPBs (E-MPBs) exhibit promoted microglia accumulation, alleviation from H 2 O 2 -induced microenvironment and inhibition of apoptosis and inflammation in vitro. In addition, E-MPBs possessed significant tissue repair and neuroprotection in vivo. These properties endowed E-MPBs with great improvement in vivo in function recovery, resulting in anti-neuroinflammation activity and excellent biocompatibility in mice SCI model. As a promising treatment for efficient SCI immunotherapy, these results demonstrate the use of exosome-sheathed biomimetic nanoparticles exocytosed by anti-inflammation cells is feasible. [ABSTRACT FROM AUTHOR]

The article presents editor's comments on issues raised by the paper "Psycho-Endocrine-Immune Response to Mindfulness-Based Stress Reduction in Individuals Infected with the Human Immunodeficiency Virus: A Quasi-experimental Study," on the mindfulness meditation technique and other behavioral interventions to treat human immunodeficiency virus (HIV) and other disorders. Authors conclude that the literature is inconsistent with scattered evidence when gauging positive effects on immune function in patients with HIV. When looking at psychological effects in nonpatient populations, they conclude that mindfulness-based stress reduction has a positive effect on mood and the subjective evaluation of physical and psychological symptoms.

Summary: The immune system plays a critical role in protecting the host against infection but is subject to numerous levels of control that are necessary to prevent pathological, tissue-damaging responses. Inappropriate inflammatory immune responses to self-antigens, innocuous commensal microorganisms, or environmental antigens can lead to chronic, debilitating, and degenerative diseases. Regulatory T cells have an essential, non-redundant, and dominant function in preventing pathological immune responses, as shown by the development of systemic fatal autoimmunity in humans and animals with a genetic deficiency in regulatory T cells. In addition to controlling immune responses, there is a growing understanding that regulatory T cells also contribute directly to tissue homeostasis by promoting tissue regeneration and repair. For these reasons, the prospect of enhancing regulatory T-cell numbers and/or function in patients represents an appealing therapeutic opportunity with potential applications in many diseases, including some where the pathological role of the immune system has only recently been recognized. Approaches to enhance regulatory T cells are now starting to be explored in clinical studies in humans. This review series brings together papers highlighting the Treg-enhancing approaches that are most advanced clinically and examples of therapeutic opportunities based on our growing understanding of regulatory T-cell functions. [ABSTRACT FROM AUTHOR]

Immunogenic cell death (ICD) arises when cells are under stress, and their membranes are damaged. They release damage‐associated molecular patterns (DAMPs) that stimulate and drive the type and magnitude of the immune response. In the presence of an antigen, DAMPs ride the longevity and efficacy of antigen‐specific immunity. Yet, no tool can induce the controlled ICD with predictable results. A peptide‐based tool, [II], is designed that aggregates in the cell and causes cell membrane damage, generates ICD and DAMPs release on various cell types, and hence can act as an adjuvant. An influenza vaccine is prepared by combining [II] with influenza hemagglutinin (HA) subunit antigens. The results show that [II] induced significantly higher HA‐specific immunoglobulin G1 (IgG1) and IgG2a antibodies than HA‐only immunized mice, while the peptide itself did not elicit antibodies. This paper demonstrates the first peptide‐aggregation induced immunogenic rupture (PAIIR) approach as a vaccine adjuvant. PAIIR is a promising adjuvant with a high potential to promote universal protection upon influenza HA vaccination. [ABSTRACT FROM AUTHOR]

The major histocompatibility complex (MHC) in chickens (Gallus gallus) is located on the 16th micro chromosome, of the avian genome. As in other species, it has a strong association with genetic resistance to diseases. This multigenic feature is particularly desired for the selection of this species, in particular because of its relationship with animal welfare. This paper aims to review the knowledge on the analysis of the variability of MHC-B in chickens and its analysis methodologies, and a synthesis of the work done on Campero INTA chickens. [ABSTRACT FROM AUTHOR]

Food allergies are of great public health concern due to their rising prevalence. Our understanding of how the immune system reacts to food remains incomplete. Allergic responses vary between individuals with food allergies. This variability could be caused by genetic, environmental, hormonal, or metabolic factors that impact immune responses mounted against allergens found in foods. Peanut (PN) allergy is one of the most severe and persistent of food allergies, warranting examination into how sensitization occurs to drive IgE-mediated allergic reactions. In recent years, much has been learned about the mechanisms behind the initiation of IgE-mediated food allergies, but additional questions remain. One unresolved issue is whether sex hormones impact the development of food allergies. Sex differences are known to exist in other allergic diseases, so this poses the question about whether the same phenomenon is occurring in food allergies. Studies show that females exhibit a higher prevalence of atopic conditions, such as allergic asthma and eczema, relative to males. Discovering such sex differences in allergic diseases provide a basis for investigating the mechanisms of how hormones influence the development of IgE-mediated reactions to foods. Analysis of existing food allergy demographics found that they occur more frequently in male children and adult females, which is comparable to allergic asthma. This paper reviews existing allergic mechanisms, sensitization routes, as well as how sex hormones may play a role in how the immune system reacts to common food allergens such as PN. [ABSTRACT FROM AUTHOR]

In this paper, a delayed-within-host-dengue infection model with mitosis and immune response is analyzed. The basic reproduction number is calculated and a detailed discussion on the local and global dynamics of the model is conducted. By using comparison arguments, it is shown that when the basic reproduction number is less than unity, the infection-free equilibrium is globally asymptotically stable. When the basic reproduction number is greater than unity, the existence of Hopf bifurcation and stability switch at the immunity-activated infection equilibrium of the model with or without delay is established. Furthermore, by means of Lyapunov functional and LaSalle's invariance principle, sufficient conditions are obtained for the global stability of the immunity-activated infection equilibrium. Numerical simulations are given to illustrate the main theoretical results. The normal form is calculated to analyze some properties of the bifurcation periodic solution when the time delay is absent. Moreover, we carry out sensitivity analysis on basic reproduction number to determine crucial parameters that affect the stability of each of feasible equilibrium. [ABSTRACT FROM AUTHOR]

The anthraquinones (AQs) and derivatives are widely distributed in nature, including plants, fungi, and insects, with effects of anti-inflammation and anti-oxidation, antibacterial and antiviral, anti-osteoporosis, anti-tumor, etc. Inflammation, including acute and chronic, is a comprehensive response to foreign pathogens under a variety of physiological and pathological processes. AQs could attenuate symptoms and tissue damages through anti-inflammatory or immuno-modulatory effects. The review aims to provide a scientific summary of AQs on immune responses under different pathological conditions, such as digestive diseases, respiratory diseases, central nervous system diseases, etc. It is hoped that the present paper will provide ideas for future studies of the immuno-regulatory effect of AQs and the therapeutic potential for drug development and clinical use of AQs and derivatives. [ABSTRACT FROM AUTHOR]

Recently, bistable viral infection systems have attracted increased attention. In this paper, we study bistability and robustness for virus infection models with nonmonotonic immune responses in viral infection systems. The results show that the existing transcritical bifurcation undergoes backward or forward bifurcation in viral infection models with nonmonotonic immune responses. Our investigation demonstrates that the backward bifurcation threshold is the elite control threshold. When the immune intensity is greater than the elite control threshold, the virus will be under elite control; when the immune intensity is less than the elite control threshold, the virus may rebound. We also give a new definition of robustness to characterize bistable systems. [ABSTRACT FROM AUTHOR]

Currently, SARS-CoV-2 spike receptor-binding-domain (RBD)-based vaccines are considered one of the most effective weapons against COVID-19. During the first step of assessing vaccine immunogenicity, a mouse model is often used. In this paper, we tested the use of five experimental animals (mice, hamsters, rabbits, ferrets, and chickens) for RBD immunogenicity assessments. The humoral immune response was evaluated by ELISA and virus-neutralization assays. The data obtained show hamsters to be the least suitable candidates for RBD immunogenicity testing and, hence, assessing the protective efficacy of RBD-based vaccines. [ABSTRACT FROM AUTHOR]

The highly virulent Newcastle disease virus (NDV) isolates typically result in severe systemic pathological changes and high mortality in Newcastle disease (ND) illness, whereas avirulent or low-virulence NDV strains can cause subclinical disease with no morbidity and even asymptomatic infections in birds. However, understanding the host's innate immune responses to infection with either a highly virulent strain or an avirulent strain, and how this response may contribute to severe pathological damages and even mortality upon infection with the highly virulent strain, remain limited. Therefore, the differences in epigenetic and pathogenesis mechanisms between the highly virulent and avirulent strains were explored, by transcriptional profiling of chicken embryonic visceral tissues (CEVT), infected with either the highly virulent NA-1 strain or the avirulent vaccine LaSota strain using RNA-seq. In our current paper, severe systemic pathological changes and high mortality were only observed in chicken embryos infected with the highly virulent NA-1 strains, although the propagation of viruses exhibited no differences between NA-1 and LaSota. Furthermore, virulent NA-1 infection caused intense innate immune responses and severe metabolic disorders in chicken EVT at 36 h post-infection (hpi), instead of 24 hpi, based on the bioinformatics analysis results for the differentially expressed genes (DEGs) between NA-1 and LaSota groups. Notably, an acute hyperinflammatory response, characterized by upregulated inflammatory cytokines, an uncontrolled host immune defense with dysregulated innate immune response-related signaling pathways, as well as severe metabolic disorders with the reorganization of host–cell metabolism were involved in the host defense response to the CEVT infected with the highly virulent NA-1 strain compared to the avirulent vaccine LaSota strain. Taken together, these results indicate that not only the host's uncontrolled immune response itself, but also the metabolic disorders with viruses hijacking host cell metabolism, may contribute to the pathogenesis of the highly virulent strain in ovo. [ABSTRACT FROM AUTHOR]

We are frequently faced with a large collection of antibodies, and want to select those with highest affinity for their cognate antigen. When developing a first-line therapeutic for a novel pathogen, for instance, we might look for such antibodies in patients that have recovered. There exist effective experimental methods of accomplishing this, such as cell sorting and baiting; however they are time consuming and expensive. Next generation sequencing of B cell receptor (BCR) repertoires offers an additional source of sequences that could be tapped if we had a reliable method of selecting those coding for the best antibodies. In this paper we introduce a method that uses evolutionary information from the family of related sequences that share a naive ancestor to predict the affinity of each resulting antibody for its antigen. When combined with information on the identity of the antigen, this method should provide a source of effective new antibodies. We also introduce a method for a related task: given an antibody of interest and its inferred ancestral lineage, which branches in the tree are likely to harbor key affinity-increasing mutations? We evaluate the performance of these methods on a wide variety of simulated samples, as well as two real data samples. These methods are implemented as part of continuing development of the partis BCR inference package, available at https://github.com/psathyrella/partis. Comments: Please post comments or questions on this paper as new issues at https://git.io/Jvxkn. Author summary: Antibodies form part of the adaptive immune response, and are critical to both naturally acquired immunity and vaccine response. Next generation sequencing of the B cell receptor (BCR) repertoire provides a broad and highly informative view of the DNA sequences from which antibodies arise. In many cases we would like to identify which of these BCR sequences correspond to antibodies with the highest affinity for a particular antigen. Existing experimental methods of selecting antibodies are effective, but time-consuming and expensive. In this paper we introduce new computational methods that use evolutionary information from the family of related BCR sequences to predict the affinity of each resulting antibody for its corresponding foreign antigen. When combined with information on the identity of this antigen (which we do not attempt to predict), these methods should provide a source of effective new antibodies that can then be experimentally synthesized and tested for function. [ABSTRACT FROM AUTHOR]

Use of multi-strain probiotics in poultry nutrition provides advantages, including promoting microbial diversity in the birds' gut. Less investigated, as compared to broilers, is how application of probiotics affects performance and health of Japanese quails. Up to date effects of either probiotics based on a single microorganism or using a single dose of probiotic were investigated. The aim of the study was to investigate the effect of gradual levels of multi-strain probiotic applied in the Japanese quails' diet on their performance, carcass, microbiological and immunological parameters. Total of 240 Japanese quail mixed sex chicks were randomly selected into four treatments: 0.15, 0.10, 0.05 g/l of the probiotic and control group not provided with probiotic. Body weight gain (BWG), feed intake (FI), feed conversion ratio (FCR), carcass characteristics, selected gut microbiome species and sheep red blood cell (SRBC) immunoglobulin IgT, IgG and IgM antibodies were determined. Repeated measures ANOVA was performed on parameters related to productive performance of the birds, while one-way ANOVA on all other parameters using SAS software v 9.4. FI was the highest in the control group (16.84±2.19) and did not differ significantly between other groups (from 16.53±2.12 to 15.18±1.86). FCR was the highest in the control and the lowest dose group (3.15±0.28 and 3.07±0.27), as compared to two other groups of birds which received multi-strain probiotic (2.8±0.23 and 2.77±0.24, respectively). Birds in the control group and birds which received the lowest dose of the probiotic had lower counts of IgT (5.63±0.26 and 5.75±0.25, respectively) and IgG (4.00±0.38 and 4.13±0.3, respectively), as compared to two other treatment groups which received the multi-strain probiotic. Birds which did not receive the multi-strain probiotic had significantly lower levels of Lactobacillus (6.98±0.01), as compared to other birds, while those in the control group and which received lowest amount of probiotic had significantly higher levels of E.Coli (6.67±0.01). Multi-strain probiotic had overall positive effect on the selected parameters of Japanese quails' performance and health, while efficacy varied depending on dosage. [ABSTRACT FROM AUTHOR]

Presents the study entitled “Evaluation of the Immune Response and Efficacy in Chickens of Vaccinces Prepared from P. multocida Capsular Type A Grown in Iron-Depleted Conditions,” at the 2004 Spring Meeting of the WPSA UK Branch.

• OMVs from Bordetella bronchiseptica elicit immune responses in macrophages. • Host Defense Peptides modulate the immune responses differently for sOMV and hOMVs. • Signaling via human TLRs hTLR2, hTLR4, hTLR5 and hTLR9 is stimulated by OMVs. • hTLR2- and hTLR4-mediated signaling can be downregulated by LL-37 and K9CATH. • Uptake of OMVs plays a minimal role in eliciting an immune response in macrophages. Antibiotic resistance is increasing and one strategy to prevent resistance development is the use of bacterial vaccines. For Gram-negative bacteria, natural outer membrane vesicles (OMVs) could be used for vaccine development. These vesicular structures are naturally produced by all Gram-negative bacteria and contain several antigens in their native environment. However, despite that the presence of lipopolysaccharide (LPS) may aid as intrinsic adjuvant, there is a risk that it may also cause undesired immune responses. Therefore, molecules to dampen LPS-induced toll-like receptor (TLR) 4 activation may be needed. Here host defense peptides (HDPs), like cathelicidins, can play an important role. They have been shown to interact with LPS and thereby neutralize LPS-induced TLR4 activation. However, there is currently no knowledge about neutralization in an OMV-based setting. Therefore, in this paper the immune modulating capacity of HDPs was investigated after macrophage stimulation with either spontaneous or heat-induced B. bronchiseptica OMVs. This revealed that the cathelicidins LL-37, CATH-2, PMAP-36 and K9CATH were able to modulate immune responses. Interestingly, immune modulation by these cathelicidins was different for spontaneous compared to heat-induced OMVs. Interaction studies revealed that the mode of binding of cathelicidins to OMVs slightly differed between OMV classes. Furthermore, TLR screening revealed that TLR2, 4, 5 and 9 were involved in stimulation of macrophages by OMVs, with TLR4-mediated activation being the most important pathway. Uptake of OMVs did not play a major role in macrophage activation. Taken together, this study shows how OMVs can activate macrophages and how cathelicidins may modulate these immune responses. [ABSTRACT FROM AUTHOR]

In this paper, a new delayed within host model for dengue fever with immune response and Beddington–DeAngelis incidence is investigated. The basic reproduction number is computed. In addition, a detailed analysis on the local and global dynamics of the model is conducted. Finally, sensitivity analysis is carried out on basic reproduction number and numerical simulations are given to elucidate our theoretical results. [ABSTRACT FROM AUTHOR]

Immunogenicity to biologics is often observed following dosing in human subjects during clinical trials. Both product and host specific factors may be implicated in contributing to a potential immune response. However, even if such risk factors are identified and eliminated as part of the rational quality by design approaches, the outcome in clinic can be uncertain and challenging to predict. Several tools have been employed to identify these risk factors and consequent mitigation approaches implemented prior to dosing in humans. However, the complexity of the immune system with an interplay of network of immune cells involved in driving a long- term immune response as well as patient characteristics, can make it challenging to predict the outcome in clinic. This perspective will provide an insight into recent advances in the risk assessment approaches that are utilized during preclinical stage of development of a biologic. The outputs from such tools can help to rank order and select the most optimal candidate with the least likelihood of an immune response and can further drive the development of a clinical bioanalytical and immunogenicity monitoring strategy. Such a strategy can be proactively shared with the regulators along with the proposal to streamline clinical immunogenicity and personalizing the outcome based on pharmacogenomics and other patient-related factors. This paper provides a roadmap on performing risk assessments through a systematic identification of risks and their mitigations wherever possible. Recommendations on incorporating the key components of such risk assessments as part of the new regulatory submissions are also provided. Shorter abstract Immunogenicity to biologics is common during clinical trials. Both product and host specific factors have been implicated. Several risk assessment tools can be used to identify and mitigate the risk factors responsible for immunogenicity. An insight into recent advances in the risk assessment approaches will be presented. The outputs can define a risk score and guide the clinical bioanalytical and immunogenicity monitoring strategy. A roadmap on performing risk assessments through a systematic identification of risks and their mitigations wherever possible is provided. Best practices for a risk assessment strategy and recommendations on the content for IND and the Integrated summary of Immunogenicity are also provided. [ABSTRACT FROM AUTHOR]

Background: Typhoid fever is an endemic disease in many low-income and middle-income countries. The 2018 WHO position paper recommends that countries should consider typhoid vaccination in high-risk groups and for outbreak control. To address the typhoid vaccine supply and demand gap, a typhoid Vi polysaccharide-diphtheria toxoid (Vi-DT) conjugate vaccine development effort was undertaken to achieve WHO prequalification and contribute to the global supply of typhoid conjugate vaccine. The main aim of this study was to show immune non-inferiority of the Vi-DT vaccine compared with the WHO prequalified Vi polysaccharide-tetanus toxoid (Vi-TT) conjugate vaccine (Typbar TCV; Bharat Biotech India, Hyderabad, India) in participants of various ages from an endemic country.Methods: We did an observer-blind, active-controlled, randomised, non-inferiority, phase 3 trial at four hospitals in Kathmandu, Dhulikhel, Dharan, and Nepalgunj in Nepal. Eligible participants were healthy individuals aged 6 months to 45 years for whom informed consent was obtained, were willing to follow the study procedures and were available for the duration of the study. Patients with an acute or chronic illness that could interfere with interpretation of the study endpoints, or who were involved in any other clinical trial were excluded. Participants were randomly assigned (1:1:1:1) by block randomisation (block size of four and eight), stratified by age (6 months to <2 years, 2 years to <18 years, and 18 years to 45 years), into one of four groups (A-D). Participants in groups A-C received a single dose (25 μg; 0·5 mL) of Vi-DT test vaccine via intramuscular injection from one of three good manufacturing practice lots (group A received lot 1, group B received lot 2, and group C received lot 3), and those in group D received a single dose (25 μg; 0·5 mL) of the Vi-TT vaccine via intramuscular injection. All participants, site staff (except for those who administered the study vaccines), and those assessing the outcomes were masked to group assignment. The co-primary endpoints were: (1) non-inferiority of immunogenicity of the Vi-DT vaccine (pooled groups A-C) versus the Vi-TT vaccine (group D), measured by the anti-Vi IgG seroconversion rate at 4 weeks after vaccination; and (2) the lot-to-lot consistency of the Vi-DT vaccine, measured by immune equivalence of the anti-Vi IgG geometric mean titre (GMT) at 4 weeks after receipt of the three Vi-DT vaccine lots (lot 1 vs lot 2, lot 1 vs lot 3, and lot 2 vs lot 3). Non-inferiority of the Vi-DT vaccine compared with the Vi-TT vaccine was shown if the lower limit of the 97·5% CI for the difference between the seroconversion rates in Vi-DT vaccine groups A-C combined versus Vi-TT vaccine group D was above the predefined non-inferiority margin of -10%. Lot-to-lot immune equivalence was shown if the upper and lower bounds of the two-sided 99·17% CI around the GMT ratio for each pairwise lot-to-lot comparison was between 0·67 and 1·50, which is the predefined equivalence margin recommended by WHO. The co-primary immunogenicity endpoints were assessed in all randomised participants who had received their assigned vaccine and had completed at least one post-baseline immunogenicity assessment. Safety was descriptively summarised by group and age strata, and was assessed in all participants who had received one dose of the investigational vaccine. The trial is registered with ClinicalTrials.gov, NCT03933098.Findings: Between Nov 20, 2019, and March 10, 2020, 1854 individuals were screened, of whom 1800 were enrolled and randomly assigned to groups A-D (450 participants in each group). 1786 (99·2%; 443 in group A, 450 in group B, 447 in group C, and 446 in group D) were included in the immunogenicity assessments at 4 weeks post vaccination, and all 1800 participants were included in the safety analysis. In the immunogenicity analysis, the anti-Vi-IgG seroconversion rate in all age strata was 99·33% (97·5% CI 98·61 to 99·68; 1331 of 1340 participants) in Vi-DT vaccine groups A-C and 98·88% (97·10 to 99·57; 441 of 446) in Vi-TT vaccine group D. The difference in seroconversion rates between Vi-DT vaccine groups A-C combined versus Vi-TT group D was 0·47% (97·5% CI -0·68 to 1·61), indicating non-inferiority of the Vi-DT vaccine. Anti-Vi-IgG GMT ratios at 4 weeks post-vaccination were 1·02 (99·17% CI 0·85 to 1·22) for lot 1 versus lot 2, 1·02 (0·85 to 1·23) for lot 1 versus lot 3, and 1·01 (0·84 to 1·21) for lot 2 versus lot 3, indicating lot-to-lot equivalence according to the predefined, WHO-recommended equivalence margin. The proportion of participants reporting adverse events was similar between Vi-DT vaccine groups A-C and Vi-TT vaccine group D; 260 (19·3%) of 1350 participants in Vi-DT vaccine groups A-C and 115 (25·6%) of 450 in Vi-TT vaccine group D reported solicited adverse events within 7 days after vaccination, and 208 (15·4%) in Vi-DT vaccine groups A-C and 76 (16·9%) in Vi-TT vaccine group D reported unsolicited adverse events within 4 weeks after vaccination. Seven serious adverse events (four [0·3%] participants in Vi-DT vaccine groups A-C and three [0·7%] in Vi-TT vaccine group D), including one death in the Vi-TT vaccine group, were reported during the 24-week follow-up period, none of which were considered related to the investigational product.Interpretation: When administered as a single dose, the Vi-DT test vaccine was safe, immunogenic, and non-inferior to the Vi-TT vaccine at 4 weeks post vaccination. Equivalent immunogenicity of the three lots of Vi-DT vaccine was also shown, supporting the manufacturing process of this vaccine. Once prequalified by WHO, this vaccine could be an option for purchase by UN agencies.Funding: The Bill & Melinda Gates Foundation.Translation: For the Nepali translation of the abstract see Supplementary Materials section. [ABSTRACT FROM AUTHOR]

Simple Summary: This paper presents an extended version of the Cox regression model to examine heterogeneous effects of risk factors on disease subtypes defined by a continuous biomarker. This approach can be easily applied to cancer studies and is accessible to researchers via user-friendly R scripts. Molecular pathologic diagnosis is important in clinical (oncology) practice. Integration of molecular pathology into epidemiological methods (i.e., molecular pathological epidemiology) allows for investigating the distinct etiology of disease subtypes based on biomarker analyses, thereby contributing to precision medicine and prevention. However, existing approaches for investigating etiological heterogeneity deal with categorical subtypes. We aimed to fully leverage continuous measures available in most biomarker readouts (gene/protein expression levels, signaling pathway activation, immune cell counts, microbiome/microbial abundance in tumor microenvironment, etc.). We present a cause-specific Cox proportional hazards regression model for evaluating how the exposure–disease subtype association changes across continuous subtyping biomarker levels. Utilizing two longitudinal observational prospective cohort studies, we investigated how the association of alcohol intake (a risk factor) with colorectal cancer incidence differed across the continuous values of tumor epigenetic DNA methylation at long interspersed nucleotide element-1 (LINE-1). The heterogeneous alcohol effect was modeled using different functions of the LINE-1 marker to demonstrate the method's flexibility. This real-world proof-of-principle computational application demonstrates how the new method enables visualizing the trend of the exposure effect over continuous marker levels. The utilization of continuous biomarker data without categorization for investigating etiological heterogeneity can advance our understanding of biological and pathogenic mechanisms. [ABSTRACT FROM AUTHOR]

Understanding the T-cell response to SARS-CoV-2 is key in patients who lack antibody production. We demonstrate the applicability of a functional assay to measure the T-cell response in a cohort of patients with immunodeficiency. T-cell responses to COVID are now linked to improved outcomes. This paper demonstrates a method to robustly test responses for routine diagnostic use in healthy controls and those unable to make a detectable antibody response due to underlying immune deficiency (primary or acquired). [ABSTRACT FROM AUTHOR]

Vaccines against bovine babesiosis must, ideally, induce a humoral immune response characterized by neutralizing antibodies against conserved epitopes and a cellular Th1 immune response. In Babesia bovis , proteins such as AMA-1, MSA-2c, and RAP-1 have been characterized and antibodies against these proteins have shown a neutralizing effect, demonstrating the implication of B and T-cell epitopes in the immune response. There is evidence of the existence of B and T-cell epitopes in these proteins, however, it remains to be defined, the presence of conserved peptides in strains from around the world containing B and T-cell epitopes, and their role in the generation of a long-lasting immunity. The aim in this paper was to identify peptides of Babesia bovis AMA-1, MSA-2c, and RAP-1 that elicit a neutralizing and long-lasting Th1 immune response. Peptides containing B-cell epitopes of AMA-1, MSA-2c and RAP-1, were identified. The immune response generated by each peptide was characterized in cattle. All peptides tested induced antibodies that recognized intraerythrocytic parasites, however, only 5 peptides generated neutralizing antibodies in vitro : P2AMA-1 (6.28%), P3MSA-2c (10.27%), P4MSA-2c (10.42%), P1RAP-1 (32.45%), and P4RAP-1 (36.98%). When these neutralizing antibodies were evaluated as a pool, the inhibition percentage of invasion increased to 52.37%. When the T cellular response was evaluated, two peptides: P3MSA2c and P2AMA1 induced a higher percentage (>70%) of activated CD4 +/CD45RO+ T cells than unstimulated cells. Additionally, both peptides induced the production of gamma interferon (IFN−) in PBMCs from vaccinated cattle after one year proving the implication of a long-lasting Th1 immune response. In conclusion, we identified conserved peptides containing B and T-cell epitopes in antigens of B. bovis that elicit a Th1 immune response and showed evidence that peptides from the same protein elicit different immune responses, which has implication for vaccine development in bovine babesiosis. [ABSTRACT FROM AUTHOR]

Direct cardiac reprogramming, which refers to somatic cell (i.e. fibroblast) fate conversion to cardiomyocyte-like cell without transitioning through an intermediate pluripotent state, provides a novel therapeutic strategy for heart regeneration by converting resident cardiac fibroblasts to cardiomyocytes in situ. However, several limitations need to be addressed prior to clinical translation of this technology. They include low efficiency of reprogramming, heterogeneity of starting fibroblasts, functional immaturity of induced cardiomyocytes (iCMs), virus immunogenicity and toxicity, incomplete understanding of changes in the epigenetic landscape as fibroblasts undergo reprogramming, and the environmental factors that influence fate conversion. Several studies have demonstrated that a combination of enforced expression of cardiac transcription factors along with certain cytokines and growth factors in the presence of favorable environmental cues (including extracellular matrix, topography, and mechanical properties) enhance the efficiency and quality of direct reprogramming. This paper reviews the literature on the influence of the microenvironment on direct cardiac reprogramming in vitro and in vivo. [ABSTRACT FROM AUTHOR]

A mathematical model for the quantitative analysis of the interaction between cancer cells and cell-mediated immune system with two discrete-time delays, considering the role of antibodies, is studied in this paper. The model is analyzed both analytically and numerically to understand the dynamics of interaction delay and proliferation enhancement effect delay in the eradication of cancer. Hopf bifurcation occurs when one-time delay crosses the critical value in the absence of the other. It is also observed that as we increase any of the delays, it will increase the cancer burden. The analysis shows that a cancer-free state cannot be obtained solely by the killing rate of cytotoxic T-lymphocytes, but humoral response in combination with cell-mediated immune responses plays an important role to eradicate cancer. [ABSTRACT FROM AUTHOR]

HIV infection is still a serious worldwide public health problem. During the early stage of HIV infection, the number of infected cells and viruses are extremely low and the process of infection is stochastic. In this paper, we use a stochastic model consisting of continuous-time Markov chain to investigate CTL immune response and two modes of infection (viral transmission and cellular transmission). A multitype branching process is used to approximate the probability of clearance and outbreak of HIV infection near the infection-free equilibrium. In addition, we compare the dynamics of the deterministic model with the results of the stochastic model, and the differences are as follows: (1) when R 0 > 1 , the deterministic model shows HIV infection outbreak, while the stochastic model indicates a positive probability of HIV infection elimination; (2) the initial number of infected cells and viruses have no effect on the dynamics of the deterministic model, whereas the dynamics of the stochastic model are highly dependent on the initial sizes and cannot be ignored. [ABSTRACT FROM AUTHOR]

The role of the plant innate immune system in the defense and symbiosis processes becomes integral in a complex network of interactions between plants and fungi. An understanding of the molecular characterization of the plant innate immune system is crucial because it constitutes plants' self-defense shield against harmful fungi, while creating mutualistic relationships with beneficial fungi. Due to the plant-induced awareness and their complexity of interaction with fungi, sufficient assessment of the participation of the plant innate immune system in ecological balance, agriculture, and maintenance of an infinite ecosystem is mandatory. Given the current global challenge, such as the surge of plant-infectious diseases, and pursuit of sustainable forms of agriculture; it is imperative to understand the molecular language of communication between plants and fungi. That knowledge can be practically used in diverse areas, e.g., in agriculture, new tactics may be sought after to try new methods that boost crop receptiveness against fungal pathogens and reduce the dependence on chemical management. Also, it could boost sustainable agricultural practices via enhancing mycorrhizal interactions that promote nutrient absorption and optimum cropping with limited exposure of environmental contamination. Moreover, this review offers insights that go beyond agriculture and can be manipulated to boost plant conservation, environmental restoration, and quality understanding of host-pathogen interactions. Consequently, this specific review paper has offered a comprehensive view of the complex plant innate immune-based responses with fungi and the mechanisms in which they interact. [Display omitted] [ABSTRACT FROM AUTHOR]

As long as breast cancer (BC) stays under immunosurveillance, it can be controlled by treatments eliciting anticancer immune responses. However, once BC escapes immunosurveillance, it becomes therapeutically uncontrollable. A paper in the Journal for ImmunoTherapy of Cancer describes a new hormone receptor-positive BC cell line generating incurable tumors in C57BL/6 mice. [ABSTRACT FROM AUTHOR]

About 80% of the world's cattle are affected by ticks and tick-borne diseases, both of which cause significant production losses. Cattle host resistance to ticks is the most important factor affecting the economics of tick control, but it is largely neglected in tick-control programs due to technical difficulties and costs associated with identifying individual-animal variation in resistance. The present paper reviews the scientific literature to identify factors affecting resistance of cattle to ticks and the biological mechanisms of host tick resistance, to develop alternative phenotype(s) for tick resistance. If new cost-effective phenotype(s) can be developed and validated, then tick resistance of cattle could be genetically improved using genomic selection, and incorporated into breeding objectives to simultaneously improve cattle productive attributes and tick resistance. The phenotype(s) could also be used to improve tick control by using cattle management. On the basis of the present review, it is recommended that three possible phenotypes (haemolytic analysis; measures of skin hypersensitivity reactions; simplified artificial tick infestations) be further developed to determine their practical feasibility for consistently, cost-effectively and reliably measuring cattle tick resistance in thousands of individual animals in commercial and smallholder farmer herds in tropical and subtropical areas globally. During evaluation of these potential new phenotypes, additional measurements should be included to determine the possibility of developing a volatile-based resistance phenotype, to simultaneously improve cattle resistance to both ticks and biting flies. Because the current measurements of volatile chemistry do not satisfy the requirements of a simple, cost-effective phenotype for use in commercial cattle herds, consideration should also be given to inclusion of potentially simpler measures to enable indirect genetic selection for volatile-based resistance to ticks. About 80% of the world's cattle are affected by ticks and tick-borne diseases, with estimated economic losses from ticks ranging from US$20 to US$30 billion per year. Cattle host resistance is the most important factor affecting the economics of tick control, but it is largely absent in tick-control programs due to the difficulties and expense of identifying host tick resistance. The present paper reviews the literature to identify factors affecting resistance of cattle to ticks, so as to develop cost-effective ways of measuring tick resistance in cattle. The review recommends that three possible methods (haemolytic analysis; skin hypersensitivity reactions; simplified artificial tick infestations) be further developed to consistently, cost-effectively and reliably measuring cattle tick resistance. [ABSTRACT FROM AUTHOR]

In this paper, we study intra-host viral adaptation by antigenic cooperation - a mechanism of immune escape that serves as an alternative to the standard mechanism of escape by continuous genomic diversification and allows to explain a number of experimental observations associated with the establishment of chronic infections by highly mutable viruses. Within this mechanism, the topology of a cross-immunoreactivity network forces intra-host viral variants to specialize for complementary roles and adapt to the host's immune response as a quasi-social ecosystem. Here we study dynamical changes in immune adaptation caused by evolutionary and epidemiological events. First, we show that the emergence of a viral variant with altered antigenic features may result in a rapid re-arrangement of the viral ecosystem and a change in the roles played by existing viral variants. In particular, it may push the population under immune escape by genomic diversification towards the stable state of adaptation by antigenic cooperation. Next, we study the effect of a viral transmission between two chronically infected hosts, which results in the merging of two intra-host viral populations in the state of stable immune-adapted equilibrium. In this case, we also describe how the newly formed viral population adapts to the host's environment by changing the functions of its members. The results are obtained analytically for minimal cross-immunoreactivity networks and numerically for larger populations. • Antigenic cooperation is a mechanism of immune escape which provides an alternative to immune escape by continuous genomic diversification. • Intra-host viral variants create a network of cross-immunoreactivity, with each variant performing a different role to escape the host immune system. • Emergence of a new viral variant with altered antigenic features may result in a rapid rearrangement of the viral ecosystem and a change in the roles played by existing viral variants. • Emergence of a new viral variant with altered antigenic features may push the viral population into a stable state of immune escape by antigenic cooperation. • Viral transmission between two infected hosts results in the merging of two intra-host viral populations and results in changes in the functions of its members to adapt to the new host environment. [ABSTRACT FROM AUTHOR]

Exosomes, which are tiny particles released by cells, have the ability to transport various molecules, including proteins, lipids, and genetic material containing non-coding RNAs (ncRNAs). They are associated with processes like cancer metastasis, immunity, and tissue repair. Clinical trials have shown exosomes to be effective in treating cancer, inflammation, and chronic diseases. Mesenchymal stem cells (MSCs) and dendritic cells (DCs) are common sources of exosome production. Exosomes have therapeutic potential due to their ability to deliver cargo, modulate the immune system, and promote tissue regeneration. Bioengineered exosomes could revolutionize disease treatment. However, more research is needed to understand exosomes in tumor growth and develop new therapies. This paper provides an overview of exosome research, focusing on cancer and exosome-based therapies including chemotherapy, radiotherapy, and vaccines. It explores exosomes as a drug delivery system for cancer therapy, highlighting their advantages. The article discusses using exosomes for various therapeutic agents, including drugs, antigens, and RNAs. It also examines challenges with engineered exosomes. Analyzing exosomes for clinical purposes faces limitations in sensitivity, specificity, and purification. On the other hand, Nanotechnology offers solutions to overcome these challenges and unlock exosome potential in healthcare. Overall, the article emphasizes the potential of exosomes for personalized and targeted cancer therapy, while acknowledging the need for further research. [Display omitted] [ABSTRACT FROM AUTHOR]

Although novel knowledge has been acquired on the molecular landscape of glioblastoma (GBM), a relatively few steps forward have been made regarding its therapy. With the increasing use of novel immunotherapeutic drugs capable of stimulating the antitumor inflammatory response, in the last decades numerous studies aimed to characterize the tumor-associated microenvironment (TME) and its relationship with the immunogenicity of GBM. In this regard, although the tumor-associated microglia and macrophages (TAMs) and PD-L1/PD-1 axis have been emerged as one of the most relevant components of the GBM TME and one of the potential molecular pathways targetable with immunotherapy, respectively. It has been supposed that TAMs may acquire different phenotypes, switching from M1 to M2 phenotypes, with tumor-suppressive and tumor-stimulating role depending on the different surrounding conditions. PD-L1 is a type 1 transmembrane protein ligand expressed by T-cells, B-cells and antigen-presenting cells, with a main inhibitory checkpoint role on tumor immune regulation. While PD-L1 immunohistochemical expression has been extensively investigated in many cancers, its usefulness in the evaluation of GBM response rates to immunotherapy and its standardized evaluation by immunohistochemistry are still debated. The present review paper focuses on the current "state of the art" about the relationship between TME, PD-L1/PD-1 pathway and immunotherapy in GBM, also providing neuropathologists with an updated guide about the clinical trials conducted with PD-L1 and PD-1 inhibitors. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD) can lead to irreversible impairment of visual function, and the number of patients with AMD has been increasing globally. The immunoinflammatory theory is an important pathogenic mechanism of AMD, with macrophages serving as the primary inflammatory infiltrating cells in AMD lesions. Its powerful immunoinflammatory regulatory function has attracted considerable attention. Herein, we provide an overview of the involvement of macrophage-regulated immunoinflammation in different stages of AMD. Additionally, we summarize novel therapeutic approaches for AMD, focusing on targeting macrophages, such as macrophage/microglia modulators, reduction of macrophage aggregation in the subretinal space, modulation of macrophage effector function, macrophage phenotypic alterations, and novel biomimetic nanocomposites development based on macrophage-associated functional properties. We aimed to provide a basis and reference for the further exploration of AMD pathogenesis, developmental influences, and new therapeutic approaches. • Provide an overview of the involvement of macrophage-regulated immunoinflammation in AMD. • Summarize novel therapeutic approaches for AMD, focusing on targeting macrophages. • Provide a basis and reference for the further exploration of AMD. This paper is a systematic literature review. We conducted a literature search on PubMed, Web of Science, and Google Scholar for the keywords: macular degeneration [Mesh], macrophages [Mesh], aging [Mesh], therapeutics [Mesh], inflammation [Mesh], immune, complement. While writing this review, relevant citations were also cross-referenced. We selected all the experimental studies, clinical studies and reviews that fit our search. We excluded articles published before 1990. [ABSTRACT FROM AUTHOR]

It is widely acknowledged that gastric cancer seriously affects the quality of life and survival of patients. The correlation between the microbiota and gastric cancer has attracted extensive attention in recent years, nonetheless the specific mechanism of its impact on gastric cancer remain largely unclear. Recent studies have shown that in addition to its role in the host's inflammatory and immune response, the microbiota can also affect the occurrence and development of gastric cancer by affecting the expression of miRNAs. This paper brings together all currently available data on miRNAs, microbiota and gastric cancer, and preliminarily describes the relationship among them. [ABSTRACT FROM AUTHOR]

In a previous study, Ocimum gratissimum (OG) was found to have a positive effect on the immune capacity in Taiwan country chickens. This paper explores this potential further. A total of 200 one day-old male and female chickens were randomly assigned to a control group, three OG/Basal Diet groups (1 g/kg, 3 g/kg and 5 g/kg), and one Amoxicillin group. Data collected during the experiment indicated that OG supplementation produced no significant difference in growth performance but slight changes in blood characteristics. However, the different intestinal segments showed significant changes in the 3 g/kg and 5 g/kg OG groups. The haemagglutination, haemaglutination inhibition, and phytohaemaglutinin tests revealed that, compared to control, certain OG dosages produced significant increases in these levels (p< 0.05). These results indicate that OG supplementation enhances humoral immune response and cell-mediated immune response even from a considerably low dosage of 0.1%. Taken together, these findings suggest that although OG does not change growth or blood quality, the enhancements in humoral and cell-mediated immune response may improve the overall health and therefore reduce mortality of broiler chickens. [ABSTRACT FROM AUTHOR]

In this paper, we propose an optimal control problem for an HIV infection model with cellular and humoral immune responses, logistic growth of uninfected cells, cell-to-cell spread, saturated infection, and cure rate. The model describes the interaction between uninfected cells, infected cells, free viruses, and cellular and humoral immune responses. We use two control functions in our model to show the effectiveness of drug therapy on inhibiting virus production and preventing new infections. We apply Pontryagin maximum principle to study these two control functions. Next, we simulate the role of optimal therapy in the control of the infection by numerical simulations and AMPL software. [ABSTRACT FROM AUTHOR]

Live anthrax vaccine containing spores from attenuated strains STI-1 of Bacillus anthracis is used in Russia and former CIS (Commonwealth of Independent States) to prevent anthrax. In this paper we studied the duration of circulation of antibodies specific to spore antigens, the protective antigen (PA), the lethal factor (LF) and their domains (D) in donors' blood at different times after their immunization with live anthrax vaccine. The relationship between the toxin neutralization activity level and the level of antibodies to PA, LF and their domains was tested. The effect of age, gender and number of vaccinations on the level of adaptive post-vaccination immune response has been studied. It was shown that antibodies against PA-D1 circulate in the blood of donors for 1 year or more after immunization with live anthrax vaccine. Antibodies against all domains of LF and PA-D4 were detected in 11 months after vaccination. Antibodies against the spores were detected in 8 months after vaccination. A moderate positive correlation was found between the titers of antibodies to PA, LF, or their domains, and the TNA of the samples of blood serum from the donors. [ABSTRACT FROM AUTHOR]

Cancer immunotherapy has the goal of enhancing a patient's intrinsic immune processes in order to mount a successful immune response against tumor cells. Cancer cells actively employ tactics to evade, delay, alter, or attenuate the anti-tumor immune response. Immune checkpoint inhibitors (ICIs) modulate endogenous regulatory immune mechanisms to enhance immune system activation, and have become the mainstay of therapy in many cancer types. This activation occurs broadly and as a result, activation is supraphysiologic and relatively non-specific, which can lead to immune-related adverse events (irAEs), the frequency of which depends on the patient, the cancer type, and the specific ICI antibody. Careful assessment of patients for irAEs through history taking, physical exam, and routine laboratory assessments are key to identifying irAEs at early stages, when they can potentially be managed more easily and before progressing to higher grades or more serious effects. Generally, most patients with low grade irAEs are eligible for re-challenge with ICIs, and the use of corticosteroids to address an irAE is not associated with poorer patient outcomes. This paper reviews immune checkpoint inhibitors (ICIs) including their mechanisms of action, usage, associated irAEs, and their management. [ABSTRACT FROM AUTHOR]

Furazolidone (FZD) is a widely used drug in human and veterinary medicine, and has antibacterial and antiprotozoal action. Although it is widely used as a therapy in various pathological conditions, studies on the efficacy of FZD associated with immune responses are still limited. In this review, we seek to describe which immunopharmacological responses are caused by the administration of FZD. The study followed the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). A systematic review of clinical trials and in vitro and in vivo experimental studies was carried out, which resulted in 943 papers, of which 35 were considered eligible and, of these 35, 4 were selected for analysis. The studies listed indicated that administration of FZD can modulate pro- or anti-inflammatory pathways, with a probable increase in the expression of reactive oxygen species and a modulation of apoptotic pathways. [ABSTRACT FROM AUTHOR]

In this paper, the dynamics of stochastic human T‐cell leukemia virus type I (HTLV‐I) infection model with cytotoxic T lymphocyte (CTL) immune response is investigated. First, we show that the stochastic model exists as a unique positive global solution originating from the positive initial value. Second, we demonstrate that the stochastic model is stochastically permanent and stochastically ultimately bounded for any positive initial value. Third, we establish sufficient conditions for the existence of ergodic stationary distribution of the stochastic model. Fourth, the threshold R0∗ between extinction and persistence of the virus is obtained. Finally, numerical simulations are carried out to illustrate the theoretical results. [ABSTRACT FROM AUTHOR]

In this paper, with eclipse stage in consideration, we propose an HIV-1 infection model with a general incidence rate and CTL immune response. We first study the existence and local stability of equilibria, which is characterized by the basic infection reproduction number R 0 and the basic immunity reproduction number R 1 . The local stability analysis indicates the occurrence of transcritical bifurcations of equilibria. We confirm the bifurcations at the disease-free equilibrium and the infected immune-free equilibrium with transmission rate and the decay rate of CTLs as bifurcation parameters, respectively. Then we apply the approach of Lyapunov functions to establish the global stability of the equilibria, which is determined by the two basic reproduction numbers. These theoretical results are supported with numerical simulations. Moreover, we also identify the high sensitivity parameters by carrying out the sensitivity analysis of the two basic reproduction numbers to the model parameters. [ABSTRACT FROM AUTHOR]

In this paper, a deterministic model characterizing the within-host infection of Hepatitis C virus (HCV) in intrahepatic and extrahepatic tissues is presented. In addition, the model also includes the effect of the cytotoxic T lymphocyte (CTL) immunity described by a linear activation rate by infected cells. Firstly, the non-negativity and boundedness of solutions of the model are established. Secondly, the basic reproduction number R 01 and immune reproduction number R 02 are calculated, respectively. Three equilibria, namely, infection-free, CTL immune response-free and infected equilibrium with CTL immune response are discussed in terms of these two thresholds. Thirdly, the stability of these three equilibria is investigated theoretically as well as numerically. The results show that when R 01 < 1 , the virus will be cleared out eventually and the CTL immune response will also disappear; when R 02 < 1 < R 01 , the virus persists within the host, but the CTL immune response disappears eventually; when R 02 > 1 , both of the virus and the CTL immune response persist within the host. Finally, a brief discussion will be given. [ABSTRACT FROM AUTHOR]