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[Display omitted] • The immune response and inflammation in pulmonary hypertension (PH) have been systematically summarized based on recent studies. • The relationship between CC chemokines and the pathogenesis of pH is summarized in clinical and animal models. • We found that although the immune response serves as an important potential factor in the pathogenesis of PH, less attention has been paid to CC chemokines and their receptors. • We believe that a greater understanding of the relationship between PH and CC chemokines and their receptors is a pressing issue. • We believe that we need to further clarify the pathogenesis of pH and provide basis for the clinical treatment of PH. Pulmonary hypertension (PH) represents a progressive condition characterized by the remodeling of pulmonary arteries, ultimately culminating in right heart failure and increased mortality rates. Substantial evidence has elucidated the pivotal role of perivascular inflammatory factors and immune dysregulation in the pathogenesis of PH. Chemokines, a class of small secreted proteins, exert precise control over immune cell recruitment and functionality, particularly with respect to their migration to sites of inflammation. Consequently, chemokines emerge as critical drivers facilitating immune cell infiltration into the pulmonary tissue during inflammatory responses. This review comprehensively examines the significant contributions of CC chemokines in the maintenance of immune cell homeostasis and their pivotal role in regulating inflammatory responses. The central focus of this discussion is directed towards elucidating the precise immunoregulatory actions of CC chemokines concerning various immune cell types, including neutrophils, monocytes, macrophages, lymphocytes, dendritic cells, mast cells, eosinophils, and basophils, particularly in the context of pH processes. Furthermore, this paper delves into an exploration of the underlying pathogenic mechanisms that underpin the development of PH. Specifically, it investigates processes such as cellular pyroptosis, examines the intricate crosstalk between bone morphogenetic protein receptor type 2 (BMPR2) mutations and the immune response, and sheds light on key signaling pathways involved in the inflammatory response. These aspects are deemed critical in enhancing our understanding of the complex pathophysiology of PH. Moreover, this review provides a comprehensive synthesis of findings from experimental investigations targeting immune cells and CC chemokines. Aim of review : In summary, the inquiry into the inflammatory responses mediated by CC chemokines and their corresponding receptors, and their potential in modulating immune reactions, holds promise as a prospective avenue for addressing PH. The potential inhibition of CC chemokines and their receptors stands as a viable strategy to attenuate the inflammatory cascade and ameliorate the pathological manifestations of PH. Nonetheless, it is essential to acknowledge the current state of clinical trials and the ensuing progress, which regrettably appears to be less than encouraging. Substantial hurdles exist in the successful translation of research findings into clinical applications. The intention is that such emphasis could potentially foster the advancement of potent therapeutic agents presently in the process of clinical evaluation. This, in turn, may further bolster the potential for effective management of PH. [ABSTRACT FROM AUTHOR]

The advent of cancer immunotherapy has imparted a transformative impact on cancer treatment paradigms by harnessing the power of the immune system. However, the challenge of practical and precise targeting of malignant cells persists. To address this, engineered nanoparticles (NPs) have emerged as a promising solution for enhancing targeted drug delivery in immunotherapeutic interventions, owing to their small size, low immunogenicity, and ease of surface modification. This comprehensive review delves into contemporary research at the nexus of NP engineering and immunotherapy, encompassing an extensive spectrum of NP morphologies and strategies tailored toward optimizing tumor targeting and augmenting therapeutic effectiveness. Moreover, it underscores the mechanisms that NPs leverage to bypass the numerous obstacles encountered in immunotherapeutic regimens and probes into the combined potential of NPs when co-administered with both established and novel immunotherapeutic modalities. Finally, the review evaluates the existing limitations of NPs as drug delivery platforms in immunotherapy, which could shape the path for future advancements in this promising field. This paper reviews recent advances in various nanoparticle-enhanced tumor immunotherapy strategies as delivery vehicles for immune agents. [Display omitted] [ABSTRACT FROM AUTHOR]

• Exercise and hypoxia induce distinct and overlapping immune responses. • Physiological responses to both exercise and hypoxia regulate metabolism, resilience and effector functions of immune cells. • The controlled combination of exercise and hypoxia could be used to harness synergistic/complementary immune effects. • Altitude acclimatization, appropriate exercise training and nutritional strategies mitigate increased immune risks of exercising in hypoxia. Immune outcomes are key mediators of many health benefits of exercise and are determined by exercise type, dose (frequency/duration, intensity), and individual characteristics. Similarly, reduced availability of ambient oxygen (hypoxia) modulates immune functions depending on the hypoxic dose and the individual capacity to respond to hypoxia. How combined exercise and hypoxia (e.g., high-altitude training) sculpts immune responses is not well understood, although such combinations are becoming increasingly popular. Therefore, in this paper, we summarize the impact on immune responses of exercise and of hypoxia, both independently and together, with a focus on specialized cells in the innate and adaptive immune system. We review the regulation of the immune system by tissue oxygen levels and the overlapping and distinct immune responses related to exercise and hypoxia, then we discuss how they may be modulated by nutritional strategies. Mitochondrial, antioxidant, and anti-inflammatory mechanisms underlie many of the adaptations that can lead to improved cellular metabolism, resilience, and overall immune functions by regulating the survival, differentiation, activation, and migration of immune cells. This review shows that exercise and hypoxia can impair or complement/synergize with each other while regulating immune system functions. Appropriate acclimatization, training, and nutritional strategies can be used to avoid risks and tap into the synergistic potentials of the poorly studied immune consequences of exercising in a hypoxic state. [Display omitted] [ABSTRACT FROM AUTHOR]

During the on-orbit capture task of the free-floating space robot, its operating space degenerates. The dynamic coupling and dynamic singularity also affect the task operation. In this paper, a general collision-free trajectory planning method to minimize base disturbance is proposed for a free-floating dual-arm space robot. This method can realize smooth joint trajectory planning while avoiding singularity and realizing self-collision avoidance. The singularity can be effectively avoided by transforming the trajectory planning problem into a nonlinear optimization problem. The optimization function is composed of base disturbance penalty function, end effector error function and collision repulsion potential field function, which can be used to solve the optimal joint trajectory parameters. Futhermore, self-collision avoidance is achieved by combining the bacterial foraging optimization algorithm(BFOA) with the geometric vector collision-avoidance method based on artificial potential field to simplify the calculation complexity. Finally, simulations verify the effectiveness of the proposed planning framework. [ABSTRACT FROM AUTHOR]

The human immune system is studied at different scales (molecular, cellular, tissue, organism, population) with varied granularity and spatiotemporal dimensions. Innate and adaptive immune responses to viral infections are researched in vitro, in vivo, and in silico using mathematical and computational methods. The construction of computational models is an iterative and interactive process which combines existing knowledge and hypotheses (knowledge-driven approach) with empirical datasets (data-driven approach). The resulting models should ideally provide reusability, composability, and interoperability to support system simulation. The main premises of this paper are (1) computational models can be used not only for representation of existing knowledge, but also as experimental tools to demonstrate, exemplify, create, and serve as test-beds for the analysis of empirical data; and (2) computational models should be evaluated in terms of their usability (defined as a measure of how well a specified group of users can achieve predefined goals effectively, efficiently, and satisfactorily in a specified context of use). The usability measure is specified by the context information: user characteristics, their goals, and additional constraints (e.g., data availability, temporal limitations). This paper focuses on the modelling process performed by multidisciplinary teams and the usability of models for the exploration of immune response to viral infections. [ABSTRACT FROM AUTHOR]

Innate immune responses play important roles in material-induced bone formation and such roles were further explored in the current study with an emphasis on M2 macrophages and osteoclastogenesis. With the presence of M-CSF and RANKL, M0 macrophages from FVB mouse bone marrow-derived monocytes (BMMs) fused to osteoclasts with both M2 marker and osteoclast marker at day 5, and such osteoclast formation at day 5 was enhanced when the cells were treated with IL-4 at day 3. With IL-4 treatment alone for 24 h, M0 polarized into M2 macrophages. Conditioned medium of M2 macrophages enhanced osteogenic differentiation of MC3T3-E1 (pre-osteoblasts) while osteoclast conditioned medium enhanced osteogenic differentiation of CRL-12424 (osteogenic precursors). TCPs (a typical osteoinductive material) supported M2 macrophage polarization at day 4 and osteoclast formation at day 5, while TCPb (a typical non-osteoinductive material) was less effective. Moreover, osteoclasts formed on TCPs produced osteogenic factors including S1P, Wnt10B and BMP-6, resulting osteogenic differentiation of CRL-12424 cells. Similar to in vitro testing, TCPs favored M2 macrophage polarization followed by the formation of osteoclasts in vivo, as compared to TCPb. The overall data provided evidence of a coupling between M2 macrophages, osteoclasts and material-induced bone formation: osteoclasts formed from M2 macrophages secrete osteogenic cytokines to induce osteogenic differentiation of osteogenic precursor cells to finally form bone. The current findings outlined a biological mechanism of material-induced bone formation and further rationalized the use of osteoinductive materials for bone regeneration. This paper provides evidence for finding out the relationship between M2 macrophages, osteoclasts and osteogenesis in material-induced bone formation. It suggested that osteoinductive materials enhanced macrophage polarization to M2 macrophages which fuses to osteoclasts, osteoclasts subsequently secret osteogenic cytokines to differentiate finally osteogenic precursors to form bone in osteoinductive materials. The data supports scientifically the superiority of osteoinductive materials for bone regeneration in clinics. [Display omitted] [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]

Glioblastoma is one of the most aggressive tumours with a poor response to treatment and a poor prognosis for patients. One of the proteins expressed in glioblastoma tissue is CHI3L1 (YKL-40), which is upregulated and known for its angiogenesis-supporting and pro-tumour immunomodulatory effects in a variety of cancers. In this paper we present the anti-angiogenic, anti-migratory and immunomodulatory effects of the compound G721–0282, an inhibitor of CHI3L1. The inhibitor-induced changes were investigated using conventional techniques as well as the novel label-free digital holographic tomography (DHT), a quantitative phase imaging technique that allows the reconstruction of the refractive index (RI), which is used as an image contrast for 3D visualisation of living cells. DHT allowed digital staining of individual cells and intercellular structures based only on their specific RI. Quantitative spatially resolved analysis of the RI data shows that the concentration of G721–0282 leads to significant changes in the density of cells and their intracellular structures (in particular the cytoplasm and nucleus), in the volume of lipid droplets and in protein concentrations. Studies in the U-87 MG glioblastoma cell line, THP-1 monocytes differentiated into macrophages, human microvascular endothelial cells (HMEC-1) and in the spheroid model of glioblastoma composed of U-87 MG, HMEC-1 and macrophages suggest that inhibition of CHI3L1 may have potential in the antitumour treatment of glioblastoma. In this paper, we also propose a spheroid model for in vitro studies that mimics this type of tumour. [Display omitted] • Multimodal study of CHI3L1 inhibition in glioblastoma cells. • CHI3L1 inhibition is mediated by changes in pSTAT-3 phosphorylation. • G721-0282 reduces angiogenesis, cell migration and deregulates cytokine balance. • Holotomography revealed changes in the cytoskeletal density of glioblastoma cells. • Label-free quantitative analysis of changes in intracellular protein concentration. [ABSTRACT FROM AUTHOR]

Nutritional strategies during the final weeks prepartum, the close-up period, aim to reduce immune suppression and metabolic imbalances. This paper reports results of 2 observational studies. Data from 2 previous experiments (study 1) were used to investigate the associations between days fed close-up diets (DINCUD) and uterine diseases (n = 1,230). In study 2, retrospective data from animals not used in study 1 (n = 11,962) were used to investigate the associations between DINCUD and removal from the herd and long-term reproductive and productive responses. Nulliparous (lactation = 0) and parous (lactation ≥1) cows were moved to close-up pens 28 d before expected calving date, but only parous cows were fed rations with negative dietary cation-anion difference. In study 1, study personnel diagnosed retained fetal membranes, metritis, and acute metritis postpartum. Length of the close-up period was tested for its linear and quadratic effects. The β-coefficients from the multivariable analyses were used to calculate the predicted outcome for each cow. In addition, the mean (±SEM) for cows with <10, 28 ± 3, and 42 ± 3 DINCUD are reported. Metritis was associated with the interaction between DINCUD and parity-diet (nulliparous: <10 d = 31.8 ± 9.2, 28 ± 3 d = 21.8 ± 0.7, 42 ± 3 d = 29.8 ± 2.1%; parous: <10 d = 81.7 ± 2.9, 28 ± 3 d = 11.1 ± 0.3, 42 ± 3 d = 14.8 ± 1.3%). The interaction between DINCUD and parity-diet was associated with total energy-corrected milk yield (nulliparous: ≤10 d = 7.91 ± 0.03, 28 ± 3 d = 8.17 ± 0.01, 42 ± 3 d = 8.15 ± 0.01 kg × 103; parous: ≤10 d = 7.99 ± 0.05, 28 ± 3 d = 9.79 ± 0.01, 42 ± 3 d = 9.52 ± 0.03 kg × 103) and percentage of cows pregnant by 305 days in milk (DIM; nulliparous: ≤10 d = 80.4 ± 0.4, 28 ± 3 d = 83.3 ± 0.1, 42 ± 3 d = 82.8 ± 0.2%; parous: ≤10 d = 59.5 ± 0.7, 28 ± 3 d = 78.3 ± 0.1, 42 ± 3 d = 73.1 ± 0.5%). Furthermore, the interaction between DINCUD and parity-diet was associated with removal from the herd by 305 DIM (nulliparous: ≤10 d = 27.0 ± 0.5, 28 ± 3 d = 20.7 ± 0.1, 42 ± 3 d = 21.8 ± 0.1%; parous: ≤10 d = 45.1 ± 0.7, 28 ± 3 d = 31.1 ± 0.1, 42 ± 3 d = 28.1 ± 0.3%). Jersey cows that are managed to achieve 28 DINCUD may have reduced odds of uterine diseases and improved reproductive and productive performances. [ABSTRACT FROM AUTHOR]

Immunotherapy has been recently considered as a promising alternative for cancer treatment. Indeed, targeting of immune checkpoint (ICP) strategies have shown significant success in human malignancies. However, despite remarkable success of cancer immunotherapy in pancreatic cancer (PCa), many of the developed immunotherapy methods show poor therapeutic outcomes in PCa with no or few effective treatment options thus far. In this process, immunosuppression in the tumor microenvironment (TME) is found to be the main obstacle to the effectiveness of antitumor immune response induced by an immunotherapy method. In this paper, the latest findings on the ICPs, which mediate immunosuppression in the TME have been reviewed. In addition, different approaches for targeting ICPs in the TME of PCa have been discussed. This review has also synopsized the cutting-edge advances in the latest studies to clinical applications of ICP-targeted therapy in PCa. The latest findings on the immune checkpoints (ICPs) mediating immunosuppression in tumor microenvironment (TME) are reviewed. Different approaches for targeting ICPs in TME of pancreatic cancer (PCa) and the latest clinical applications are discussed. [Display omitted] [ABSTRACT FROM AUTHOR]

Mathematical modelling helps to describe the functional and causal relationships between objects in the physical world. The complexity of these models increases as more components and variables are added to maintain and observe. Differential equations are regularly used in these models, as they are able to display the interactions between several variables and describe non-linear behaviour. Differential equations are commonly used in immune response mathematical models to help describe these complex and dynamic interactions within the immune system of the organism. Time delays in the immune system are common and are often disregarded due to the low-resolution of models, which provide limited description of the specific section of immune system being studied. The few models that incorporate time delays are mostly at the epidemiological level, to track the spread of the virus in the population. In this paper we review the applications of the models based on differential equations and describe their potential utilization for the studies of immune response in SARS-CoV-2. [ABSTRACT FROM AUTHOR]

• A deterministic model to study the dynamics of human immune response to Mycobacterium tuberculosis is proposed. • The host immune response is regulated by the interleukin-10 cytokine during disease progression. • Stability analysis of the model shows a possibility of dynamical stabilization of the disease-free steady state. • The occurrence of latent infection depends on the bacterial load for a reproduction number less than unity. • The time to switch from latent to active state is critically determined by the role of interferon gamma cytokine. The use of mathematical tools to study biological processes is of necessity in determining the effects of these biological processes occurring at different levels. In this paper, we study the immune system's response to infection with the bacteria Mycobacterium tuberculosis (the causative agent of tuberculosis). The response by the immune system is either global (lymph node, thymus, and blood) or local (at the site of infection). The response by the immune system against tuberculosis (TB) at the site of infection leads to the formation of spherical structures which comprised of cells, bacteria, and effector molecules known as granuloma. We developed a deterministic model capturing the dynamics of the immune system, macrophages, cytokines and bacteria. The hallmark of Mycobacterium tuberculosis (MTB) infection in the early stages requires a strong protective cell-mediated naive T cells differentiation which is characterised by antigen-specific interferon gamma (IFN- γ). The host immune response is believed to be regulated by the interleukin-10 cytokine by playing the critical role of orchestrating the T helper 1 and T helper 2 dominance during disease progression. The basic reproduction number is computed and a stability analysis of the equilibrium points is also performed. Through the computation of the reproduction number, we predict disease progression scenario including the latency state. The occurrence of latent infection is shown to depend on a number of effector function and the bacterial load for R 0 < 1. The model predicts that endemically there is no steady state behaviour; rather it depicts the existence of the MTB to be a continuous process progressing over a differing time period. Simulations of the model predict the time at which the activated macrophages overcome the infected macrophages (switching time) and observed that the activation rate (ω) correlates negatively with it. The efficacy of potential host-directed therapies was determined by the use of the model. [ABSTRACT FROM AUTHOR]

Currently, most classification algorithms may suffer from serious misclassification when faced with unbalanced or new data, for lacking feedback and update capability. Many existing classification methods learn from the continuous learning mechanism in the biological immune system to realize the learning of new data. However, these methods in classifying new data, because of the lack of feedback, lead to a search for a long time, even may deviate from the correct results. Humans can make the immune response proceed to a certain extent as they wish through a variety of intervention techniques. Motivated by this, this paper proposes a continual learning classification method with human-in-the-loop (H-CLCM) based on the artificial immune system. H-CLCM adjusts parameters online corresponding to misidentified data by integrating human experience during the testing phase. This enables it not only to converge to an accurate prediction model at minimal cost but also to have the capability to learn new classes of data without retraining the classifier. Experiments on 10 benchmark datasets demonstrate the performances and advantages of the proposed method. The experimental results show that H-CLCM has superior classification performance than the other approaches under the same data. • H-CLCM uses human intervention to improve its performance in real time. • H-CLCM adjusts cell parameters of error detection or increase the number of cells. • H-CLCM improves performance in identifying new types of data. [ABSTRACT FROM AUTHOR]

In this study, we report two fiber optic-biolayer interferometry (FO-BLI)-based biosensors for the rapid detection of SARS-CoV-2 neutralizing antibodies (NAbs) and binding antibodies (BAbs) in human serum. The use of signal enhancer 3,3′-diaminobenzidine enabled the detection of NAbs, anti-receptor binding domain (anti-RBD) BAbs, and anti-extracellular domain of spike protein (anti-S-ECD) BAbs up to as low as 10 ng/mL in both buffer and 100-fold diluted serum. NAbs and BAbs could be detected individually over 7.5 and 13 min, respectively, or simultaneously by prolonging the detection time of the former. The protocol for the detection of BAbs could be utilized for detection of the RBD-N501Y variant with equal sensitivity and speed. Results of the NAbs and the anti-RBD BAbs biosensors correlated well with those of the corresponding commercial assay kit. Clinical utility of the two FO-BLI biosensors were further validated using a small cohort of samples randomly taken from 16 enrolled healthy participants who received inactivated vaccines. Two potent serum antibodies were identified, which showed high neutralizing capacities toward RBD and pseudovirus. Overall, the rapid automated biosensors can be used for an individual sample measurement of NAbs and BAbs as well as for high-throughput analysis. The findings of this study would be useful in COVID-19 related studies in vaccine trials, research on dynamics of the immune response, and epidemiology studies. [Display omitted] • The paper reports rapid biosensing COVID-19 binding antibodies within 13 min. • The paper reports rapid biosensing COVID-19 neutralizing antibodies within 7.5 min. • Both antibodies can be sensitively detected individually or simultaneously. • Clinical utility of the biosensors was confirmed in sera of vaccinated volunteers. [ABSTRACT FROM AUTHOR]

The functional repertoire of intratumoral microorganisms and their local effects on the host remain poorly characterized. By revealing potentially immunogenic bacterial peptides on melanoma cells, a Nature paper provides evidence that intratumoral bacteria can directly modulate antitumor immune responses, and it details a new class of therapeutically relevant, non-human tumor antigens. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Functional outcomes following nerve repair remain suboptimal. Scarring at the repair site is a major impediment to regeneration. A biomaterial scaffold applied around the coaptation site that decreases inflammation holds great potential in reducing scarring, enhancing axonal growth, and improving functional recovery. In this study, we evaluated the effect of a macroporous nanofiber wrap, comprised of nonwoven electrospun poly-ε-caprolactone (PCL), in improving axonal regeneration in a rat sciatic nerve cut and direct repair model. Controls consisted of conventional epineurial repair. We also evaluated our wrap against the commercially available AxoGuard wrap. At five weeks following repair, the nanofiber wrap group showed a significantly decreased intraneural macrophage invasion and collagen deposition at the repair site. This was associated with increased expression of the anti-inflammatory cytokine (IL-10), decreased expression of the pro-inflammatory cytokine (TNF-α), and a decrease in the M1:M2 macrophage phenotype ratio. These findings suggest that this nanofiber wrap, with its unique macroporosity, is modulating the inflammatory response at the repair site by polarizing macrophages towards a pro-regenerative M2 phenotype. Concomitantly, a higher number of regenerated axons was noted. At sixteen weeks, the nanofiber wrap resulted in enhanced functional recovery as demonstrated by electrophysiology, neuromuscular re-innervation, and muscle histology. When compared to the AxoGuard wrap, the nanofiber wrap showed similar inflammation at the repair site and similar nerve morphometric findings, but there was a trend towards a lower overall number of macrophages invading the wrap wall. These results demonstrate favorable outcomes of the macroporous nanofiber wrap in promoting neuroregeneration and functional recovery following nerve repair. Statement of Significance Electrospun nanofiber scaffolds, with specific fiber and pore sizes, were shown to modulate the immune response and create a regenerative environment. In this paper, we present a macroporous nanofiber wrap, made of poly-ε-caprolactone, to be applied at the coaptation site in primary nerve repair. We show that it regulates the inflammatory response at the repair site and decreases scarring/fibrosis. This results in enhanced axonal regeneration, allowing a higher number of axons to cross the suture line and reach the target muscle in a timely fashion. Functional outcomes are thus improved. [ABSTRACT FROM AUTHOR]

Viral infections impose a great threat to backyard chicken production among poor rural households in developing countries. These infections limit the contribution of chicken production in improving the livelihoods of poor communities, particularly in Africa. Chicken viral infections lack treatment options; control and prevention depend primarily on adoption of vaccines and good farm management practice such as the institution of biosecurity measures. In backyard production systems, these control options are less practical and less feasible to implement. Research has demonstrated the role of genetic diversity of farmed animals and birds in explaining variation in resistance to infectious diseases and suggests that heterogeneous populations are less susceptible to disease than homogeneous populations. Local African chicken ecotypes have high genetic diversity and have demonstrated the ability to survive persistent exposure to pathogens and harsh environmental conditions. This suggests that local African chickens have the genetic potential to enhance breeding strategies for resistance to viral infections. Despite the ongoing threat of infectious disease and dynamic of diseases epidemiology attributed by climate change, little has been done to harness the genetic potential of local African chicken ecotypes to breed for resistant traits. To lay the foundation for future research, this review paper presents a summary of challenges facing current chicken viral infections control and prevention options in local African chickens, and gives an overview of documented information on the genetic diversity and population structure of local African chicken ecotypes. [ABSTRACT FROM AUTHOR]

Abstract RIG-I like receptor (RLR) signaling functions importantly in host innate immune response against RNA virus, which is tightly regulated by a number of mechanisms to prevent aberrant interferon production. The s uppressor of IK K ε (SIKE) has been identified as a suppressor of IKKε and TBK1, which are key components of RLR signaling. In this study, SIKE homologue (bcSIKE) of black carp (Mylopharyngodon piceus) has been cloned and characterized. The transcription of bcSIKE varied in host cells in response to the stimulation of LPS, poly (I:C) and viruses. bcSIKE migrated around 27 KDa in immunoblot assay and distributed in both cytoplasm and nucleus of host cell in immunofluorescent (IF) staining test. bcSIKE showed no IFN-inducing ability in reporter assay and EPC cells expressing bcSIKE showed no enhanced antiviral ability against either grass carp reovirus (GCRV) or spring viremia of carp virus (SVCV). However, bcSIKE obviously dampened the IFN-inducing ability of RLR signaling members in reporter assay when bcSIKE was co-expressed with these molecules in EPC cells. The association between bcSIKE and bcTBK1 has been identified through IF and co-immunoprecipitation (co-IP) assay. The plaque assay demonstrated clearly that bcTBK1-mediated antiviral activity in EPC cells against both GCRV and SVCV was down regulated by bcSIKE. All the data generated in this paper support the conclusion that bcSIKE interacts with bcTBK1 and inhibits bcTBK1-mediated antiviral signaling during host innate immune activation, which is reported in teleost for the first time. Highlights • bcSIKE obviously dampens the IFN-inducing ability of RLR signaling components. • bcSIKE associates with bcTBK1 directly. • bcTBK1-mediated IFN production and antiviral activity are down-regulated by bcSIKE. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is the deadliest and most common type of primary brain tumor in adults with a grim prognosis despite multimodal treatments. Dendritic cell (DC)-based immunotherapy has emerged as a promising therapeutic modality for GBM, whose efficacy is nonetheless fundamentally undermined by GBM-induced immunosuppression. Inducing emission of damage associated molecular patterns (DAMPs) is a highly effective strategy to subvert tumor-associated immunosuppression. The present work was carried out to explore the idea of subverting the GBM immunosuppressive microenvironment through DC-mediated delivery of doxorubicin-polyglycerol-nanodiamond composites (Nano-DOX), a potent DAMPs inducer demonstrated by our previous study, and thereby eliciting enhanced DC-driven anti-GBM immune response. In the in-vitro work on human cell models, Nano-DOX-loaded DC were shown to be functionally viable and release cargo drug to co-cultured GBM cells (GC). Nano-DOX-treated GC displayed not only profuse DAMPs emission but also antigen release. Enhanced activation and acquisition and presentation of GC-derived antigen were then demonstrated in DC in co-culture with GC and Nano-DOX. Consistently, co-culture with GC and Nano-DOX also activated mouse bone marrow-derived DC (mDC) which in turn stimulated mouse spleen-derived lymphocytes which ultimately suppressed co-cultured GC. Next, athymic mice bearing orthotopic human GBM xenografts were intravenously injected with Nano-DOX-loaded mDC and, 48 h later, spleen-derived lymphocytes. The presence of Nano-DOX, DAMPs emission and enhanced infiltration and activation of mDC and lymphocytes were detected in the GBM xenografts. Taken together, our results demonstrate the efficacy of DC-mediated delivery of Nano-DOX to stimulate GC immunogenicity and elicit anti-cancer immune response in the GBM. By this work, we present a novel approach with great application potential to subverting the GBM immunosuppressive microenvironment and to anti-GBM immunotherapy. Investigation has also been conducted probing the mechanisms by which Nano-DOX stimulates GC immunogenicity, which is described in a follow-up paper. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Engineering vaccine-based therapeutics for infectious diseases is highly challenging, as trial formulations are often found to be nonspecific, ineffective, thermally or hydrolytically unstable, and/or toxic. Vaccines have greatly improved the therapeutic landscape for treating infectious diseases and have significantly reduced the threat by therapeutic and preventative approaches. Furthermore, the advent of recombinant technologies has greatly facilitated growth within the vaccine realm by mitigating risks such as virulence reversion despite making the production processes more cumbersome. In addition, seroconversion can also be enhanced by recombinant technology through kinetic and nonkinetic approaches, which are discussed herein. Recombinant technologies have greatly improved both amino acid-based vaccines and DNA-based vaccines. A plateau of interest has been reached between 2001 and 2010 for the scientific community with regard to DNA vaccine endeavors. The decrease in interest may likely be attributed to difficulties in improving immunogenic properties associated with DNA vaccines, although there has been research demonstrating improvement and optimization to this end. Despite improvement, to the extent of our knowledge, there are currently no regulatory body-approved DNA vaccines for human use (four vaccines approved for animal use). This article discusses engineering DNA vaccines against infectious diseases while discussing advantages and disadvantages of each, with an emphasis on applications of these DNA vaccines. Statement of Significance This review paper summarizes the state of the engineered/recombinant DNA vaccine field, with a scope entailing "Engineering DNA vaccines against infectious diseases". We endeavor to emphasize recent advances, recapitulating the current state of the field. In addition to discussing DNA therapeutics that have already been clinically translated, this review also examines current research developments, and the challenges thwarting further progression. Our review covers: recombinant DNA-based subunit vaccines; internalization and processing; enhancing immune protection via adjuvants; manufacturing and engineering DNA; the safety, stability and delivery of DNA vaccines or plasmids; controlling gene expression using plasmid engineering and gene circuits; overcoming immunogenic issues; and commercial successes. We hope that this review will inspire further research in DNA vaccine development. [ABSTRACT FROM AUTHOR]

Abstract What are the new approaches and emerging ideas to prevent leptospirosis, a neglected bacterial re-emerging zoonotic disease? How do Leptospira interrogans escape the host defenses? We aim here to review and discuss the most recent literature that provides some answers to these questions, in particular data related to a better understanding of adaptive and innate immunity towards leptospires, and design of vaccines. This is an opinion paper, not a comprehensive review. We will try to highlight the new strategies and technologies boosting the search for drugs and vaccines. We will also address the bottlenecks and difficulties impairing the search for efficient vaccines and the many gaps in our knowledge of immunity against leptospirosis. Finally, we aim to delineate how Leptospira spp. escape the innate immune responses of Toll-Like receptors (TLR) and Nod-Like receptors (NLR). The rational use of TLR and NLR agonists as adjuvants could be key to design future vaccines against pathogenic leptospire s. [ABSTRACT FROM AUTHOR]

Most of the biological systems have long-range temporal memory and modeling of such systems by fractional-order differential equations has more advantages than classical models with integer-orders. In this paper, we provide a fractional-order Ebola virus epidemic model with delayed immune response on heterogeneous complex networks. The time-delay is introduced in the cytotoxic T-lymphocyte (CTLs) term. Based on fractional Laplace transform, some conditions on stability are derived for the model. The analysis shows that the fractional-order time-delay can effectively enrich the dynamics and strengthen the stability condition of fractional-order infection model. Finally, the derived theoretical results are justified by some numerical simulations. [ABSTRACT FROM AUTHOR]

The clade B serpins contain predominantly intracellular proteins and were reported to be involved in multiple biological functions, especially in inflammation and immune system function. However, studies about the role of the invertebrate intracellular serpins in immune responses were still deficient. Therefore, this paper focused on the functional characterization of LvserpinB3 in white shrimp Litopenaeus vannamei . The pAc5.1– Lv serpinB3-EGFP vector was transfected into Drosophila Schneider 2 (S2) cells to analyze the subcellular localization of LvserpinB3 , and fluorescent imaging showed that LvserpinB3 were mainly localized to the mitochondria. Knockdown LvserpinB3 significantly increased the mRNA expression of LvSpätzle4 ( LvSpz4 ) and LvPenaeidin4 ( LvPen4 ) upon Vibrio anguillarum infection. Moreover, GST-Pull down analysis showed that Lv serpinB3 could interact with serine protease 1 ( Lv SP1). The recombinant Lv serpinB3 (r Lv serpinB3) protein exhibited inhibitory roles on the proteolytic activity of trypsin, whereas, mutation at the P1 residue led to the disfunction of the inhibitor. Furthermore, the Lv serpinB3 and trypsin mixture were incubated with Anti -SERPINB3 antibodies, and a peptide band with an apparent molecular weight of 30 kDa were detected by western blot analysis. These findings might be valuable in understanding the potential role for Lv serpinB3 in inhibiting the target proteases during shrimp immune defences. [ABSTRACT FROM AUTHOR]

Selenium is an essential nutrient for poultry and pigs, and is important for a number of physiological processes including regulation and function of the immune system. Through its incorporation into selenoproteins, Se is involved in the regulation of oxidative stress, redox mechanisms, and other crucial cellular processes involved in innate and adaptive immune response. This review provides current knowledge on the mechanisms by which selenium can modulate the resilience to infectious diseases, and how this micronutrient can influence the capacity of the bird or the pig to maintain its productivity during an infectious challenge. In relation to the most frequent and economically important infectious diseases in poultry and pig production, the present paper considers the influence of different selenium sources (organic vs. inorganic Se) as well as dietary concentrations on the immune responses of poultry and pigs with major emphasis on the potential beneficial impact on animal resilience to common infectious diseases. [ABSTRACT FROM AUTHOR]

In mammals, STAT3 (Signal transducer and activator of transcription 3) plays an important role in growth, multiplication, differentiation and participates in inflammation, tumorigenesis, metabolic disorders and immune response. STAT3 is a protein that shuttles between the nucleus and cytoplasm. Compared to the STAT3 in cell nucleus, we did not know the function of STAT3 in cytoplasm for a long time. Some recent studies have shown that cytoplasmic STAT3 regulates autophagy through the interaction with the double-stranded RNA-activated protein kinase (PKR), which plays an important role in cellular antiviral response. Fish is a good target for developmental and comparative immunology. In the present study, we found that the expression of grass carp ( Ctenopharyngodon idella ) STAT3 ( CiSTAT3 ) was ubiquitous and significantly up-regulated under the stimulation of poly I:C. To explore the potential function of fish cytoplasmic STAT3 in the antiviral signaling pathways, in this paper we analyzed the relationship between cytoplasmic Ci STAT3 and Ci PKR. We demonstrated that the Ci STAT3 can combine with Ci PKR in vivo and in vitro . The SH2 domain of Ci STAT3 and the C-terminus of Ci PKR play an important role in this process. Moreover, the dimer of Ci STAT3 and Ci PKR was formed under normal circumstances, however, it was dissociated under the induction of poly I:C. So, we guessed the binding of Ci STAT3 and Ci PKR may regulate cell viability. It has also been shown that overexpression of Ci STAT3 in CIK cells can significantly reduce the level of p -eIF2α. On the contrary, the siRNA-mediated knockdown of Ci STAT3 and Stattic induction in CIK cells can up-regulate the p -eIF2α level. To further understand the relationship between Ci STAT3 and p -eIF2α level, we carried out the Ci PKR-knockdown experiment. The result indicated that Ci STAT3 regulated the level of p -eIF2α through binding to Ci PKR. In addition, overexpression of Ci STAT3 in CIK cells was able to improve the cell viability. These results above unraveled the molecular mechanism of fish cytoplasmic STAT3 regulating the eIF2α phosphorylation and cell viability. Therefore, the function of fish cytoplasmic STAT3 is similar to those of mammals. [ABSTRACT FROM AUTHOR]

In recent years, the implication of genomics into ecotoxicological studies has been studied closely to allow a better understanding of organism’s responses to environmental contaminants including engineering nanomaterials (ENMs). ENMs are increasingly produced for various applications including cosmetics, electronics, sports equipment, biomedicine and agriculture. Because of their small size, ENMs possess chemical or physical characteristics improved compared to the corresponding macro-sized material. As their application expend, the release of manufactured ENMs into the environment is likely to increase and concern over impacts for the aquatic ecosystem is growing. Several studies reported deleterious effect of ENMs to aquatic organisms, but there is little information about the molecular mechanisms of toxicity. The development of ecotoxicogenomic approaches will improve the characterization of cellular and molecular modes of action of ENMs to aquatic organisms and allow a better prediction of contaminants toxicity. This paper presents an overview of transciptomic/proteomic studies in freshwater and marine organisms exposed to ENMs. Overall, induction of gene expression in relations to defense mechanisms, immune responses, growth and reproduction were measured after ENMs exposures of organisms, but with different patterns depending on exposure duration and concentrations used. In addition, some studies reported a positive correlation between gene expression and cellular modifications, but not at the individual level. [ABSTRACT FROM AUTHOR]

Sepsis and septic shock are the main causes of mortality and complications in intensive care units all over the world. Luteolin is thought to have a significant role as a free radical scavenger, an anti-inflammatory agent, and an immune system modulator. The object of this review is to conduct a systematic review of the effects of luteolin and its mechanisms of action in the treatment of sepsis and its complications. The investigation was carried out in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines (PROSPERO: CRD42022321023). We searched Embase, Web of Science, Google Scholar, Science Direct, PubMed, ProQuest, and Scopus databases up to January 2023 by using the relevant keywords. Out of 1,395 records screened, 33 articles met the study criteria. In the collected papers, the main reported findings are that luteolin can affect inflammation-initiating pathways such as toll-like receptors and high mobility group box-1 and reduces the expression of genes that produce inflammatory cytokines, such as the Nod receptor protein-3, and nuclear factor kappa-light chain-enhancer of activated B cells. Luteolin also reduces the overactivity of macrophages, neutrophil extracellular traps and lymphocytes by regulating the immune response. Most studies revealed luteolin's positive benefits on sepsis through several pathways. Luteolin showed the capacity to reduce inflammation and oxidative stress, control immunological response, and prevent organ damage (in vivo studies) during sepsis. Large-scale in vivo experiments are necessary to elucidate its potential impacts on sepsis. [ABSTRACT FROM AUTHOR]

Zebrafish (Danio rerio) is an ideal model organism for exploring the ability and mechanism of tissue regeneration in the vertebrate. However, the specific cellular and molecular mechanism of caudal fin regeneration in zebrafish remains largely unclear. Therefore, we first confirmed the crucial period of fin regeneration in adult zebrafish by morphological and histological analysis. Then we performed RNA-Seq analysis of the caudal fin regeneration at three key stages, which provided some clues for exploring the mechanism of caudal fin regeneration. Moreover, we also determined the expressions of inflammatory cytokines IL-1β, IL-6, IL-8, IL-10, TGF-β, and the immune-related pathway JAK2α and STAT1b in the caudal fin of zebrafish following fin amputation by quantitative real time PCR (qPCR). Particularly, Hsp90α expression at mRNA and protein level determined by qPCR and Western blotting, respectively, and whole-mount in situ hybridization of Hsp90α were also performed in this study. The results showed that inflammatory cytokines were mainly expressed in the early period of caudal fin regeneration (1–3 days post amputation, dpa), indicating that fish immune system was involved in the fin regeneration. Furthermore, the high expression of Hsp90α in the vicinity of blastema and blood vessels of the regenerating fin suggests that Hsp90α may play a role in the initiation and promotion of caudal fin regeneration. Overall, our results provide a framework for further understanding the cellular and molecular mechanism in caudal fin regeneration. • This paper investigates the mechanism of caudal fin regeneration by using morphological, histological and RNA-seq analysis. • Zebrafish caudal fin regeneration is the mode of typical blastemal based regeneration and requires active cell proliferation. • This paper may be the first report on the spatial expression of Hsp90 in the zebrafish caudal fin by using WISH. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) have been identified as important post transcriptional regulators of gene expression. In higher vertebrates, a subset of miRNAs has been identified as important regulators of a number of key genes in immune system gene networks, and this paper review recent studies on miRNAs associated with immune response in teleost fish. Challenge studies conducted in several species have identified differently expressed miRNAs associated with viral or bacterial infection. The results from these studies point out several miRNAs that are likely to have evolutionary conserved functions that are related to immune response in teleost fish. Changed expression levels of mature miRNAs from the five miRNA genes miRNA-462, miRNA-731, miRNA-146, miRNA-181 and miRNA-223 are observed following viral as well as bacterial infection in several teleost fish. Furthermore, significant changes in expression of mature miRNAs from the five genes miRNA-21, miRNA-155, miRNA-1388, miRNA-99 and miRNA-100 are observed in multiple studies of virus infected fish while changes in expression of mature miRNA from the three genes miRNA-122, miRNA-192 and miRNA-451 are observed in several studies of fish with bacterial infections. Interestingly, some of these genes are not present in higher vertebrates. The function of the evolutionary conserved miRNAs responding to infection depends on the target gene(s) they regulate. A few target genes have been identified while a large number of target genes have been predicted by in silico analysis. The results suggest that many of the targets are genes from the host's immune response gene networks. We propose a model with expected temporal changes in miRNA expression if they target immune response activators/effector genes or immune response inhibitors, respectively. The best way to understand the function of a miRNA is to identify its target gene(s), but as the amount of genome resources for teleost fish is limited, with less well characterized genomes and transcriptomes, identifying the true target genes of the miRNAs associated with the immune response is a challenge. Identifying such target genes by applying new methods and approaches will likely be the next important step to understand the function of the miRNAs associated with immune response in teleost fish. [ABSTRACT FROM AUTHOR]

A diffusive and delayed viral dynamics model which incorporates cell-to-cell transmission, cell-mediated immune responses and general nonlinear incidence is investigated. By constructing Lyapunov functionals, it is shown that the global threshold dynamics of the model is fully determined by the basic reproduction numbers of the virus and the immune response, R 0 and R 1 . The result implies that both the basic reproduction number of the virus and the immune response might be underevaluated without considering either the virus-to-cell transmission or cell-to-cell transmission. The main results obtained in this paper extend some known results. [ABSTRACT FROM AUTHOR]

Atherosclerosis (AS) is a chronic inflammatory disease caused by disorders of lipid metabolism. Abnormal deposition of low-density lipoproteins in the arterial wall stimulates the activation of immune cells, including the adhesion and infiltration of monocytes, the proliferation and differentiation of macrophages and lymphocytes, and the activation of their functions. The complex interplay between immune cells coordinates the balance between pro- and anti-inflammation and plays a key role in the progression of AS. Therefore, targeting immune cell activity may lead to the development of more selective drugs with fewer side effects to treat AS without compromising host defense mechanisms. At present, an increasing number of studies have found that the active ingredients of traditional Chinese medicine (TCM) can regulate the function of immune cells in multiple ways to against AS, showing great potential for the treatment of AS and promising clinical applications. In this paper, we review the mechanisms of immune cell action in AS lesions and the potential targets and/or pathways for immune cell regulation by the active ingredients of TCM to promote the understanding of the immune system interactions of AS and provide a relevant basis for the use of active ingredients of TCM as natural adjuvants for AS immunotherapy. [Display omitted] ● The immune system plays an important role in the progression of atherosclerosis. ● The active ingredients of TCM regulate the state and function of immune cells. ● The active ingredients of TCM can against atherosclerosis through immune pathways. ● TCMs are promising immunotherapy adjuvants for anti-atherosclerosis. [ABSTRACT FROM AUTHOR]

In the last decades a dramatic loss of Apis mellifera hives has been reported in both Europe and USA. Research in this field is oriented towards identifying a synergy of contributing factors, i.e. pathogens, pesticides, habitat loss and pollution to the weakening of the hive. Cadmium (Cd) is a hazardous anthropogenic pollutant whose effects are proving to be increasingly lethal. Among the multiple damages related to Cd contamination, some studies report that it causes immunosuppression in various animal species. The aim of this paper is to determine whether contamination by Cd, may have a similar effect on the honey bees’ immunocompetence. Our results, obtained by immune challenge experiments and confirmed by structural and ultrastructural observations show that such metal causes a reduction in immunocompetence in 3 days Cd exposed bees. As further evidence of honey bee response to Cd treatment, Energy Dispersive X-ray Spectroscopy (X-EDS) has revealed the presence of zinc (Zn) in peculiar electron-dense granules in fat body cells. Zn is a characteristic component of metallothioneins (MTs), which are usually synthesized as anti-oxidant and scavenger tools against Cd contamination. Our findings suggest that honey bee colonies may have a weakened immune system in Cd polluted areas, resulting in a decreased ability in dealing with pathogens. [ABSTRACT FROM AUTHOR]

The combination of increased genetic potential and changes in management strategies (i.e., antibiotic-free, no antibiotics ever, and every day feeding of replacement pullets) influences the nutritional needs of poultry. Traditionally, nutritionists have focused on meeting the amino acid needs for production performance and yield however, increasing specific amino acid concentrations can benefit gastrointestinal development and integrity, enhance immune response potential, influence behavior, and benefit sustainability. Commercialization of additional feed grade amino acids beyond methionine, lysine, and threonine, enables targeted increases to achieve these benefits. As such, this paper addresses the functional roles of amino acids in meeting poultry production, health, and sustainability goals. [ABSTRACT FROM AUTHOR]

Tumor-derived extracellular vesicles (EVs) are key immune regulators of the tumor microenvironment. They reshape the immune microenvironment and prevent antitumor immune responses via their immunosuppressive cargo, thereby determining cancer responsiveness to treatment. In the immune microenvironment of melanoma, tumor-derived EVs influence tumor progression by regulating innate and adaptive immune responses. Tumor-derived EV-based therapy is a cutting-edge and promising strategy for inhibiting melanoma progression and enhancing antitumor immunity. This review aimed to summarize the regulatory roles of EVs in the immune responses and immunotherapy of patients with melanoma. This paper provided insights into future exploration directions and potential clinical strategies targeting EVs for melanoma treatment. [Display omitted] • The process of EVs biogenesis and release. • The role of EVs in regulating the immune response in melanoma. • The role of EVs in tumor immunotherapy. [ABSTRACT FROM AUTHOR]

This paper describes a model of the immunologic response of latent viruses and a donor kidney in a renal transplant recipient. An optimal control problem with state variable inequality constraints is considered to maintain the balance between over-suppression where latent viruses are reactivated and under-suppression where the transplanted kidney is rejected. A feedback methodology based on the model predictive control (MPC) method is proposed to design (sub)optimal treatment regimes. In addition, the problem of implementing the MPC methodology and nonlinear Kalman filter with inaccurate or incomplete observation data and long measurement periods is addressed. The results of numerical simulations show that a (sub)optimal dynamic immunosuppression therapy method can help strike a balance between the over-suppression and under-suppression of the immune system. [ABSTRACT FROM AUTHOR]

In this paper, we study a diffusive and delayed virus dynamics model with Beddington–DeAngelis incidence and CTL immune response. By constructing Lyapunov functionals, we show that if the basic reproductive number is less than or equal to one, then the infection-free equilibrium is globally asymptotically stable; if the immune reproductive number is less than or equal to one and the basic reproductive number is greater than one, then the immune-free equilibrium is globally asymptotically stable; if the immune reproductive number is greater than one, then the interior equilibrium is globally asymptotically stable. [ABSTRACT FROM AUTHOR]

In this paper, we establish and investigate an HIV infection model with treatments and delayed immune response and study its dynamical behaviors. By identifying a critical parameter, we show that if the effectiveness of RT inhibitor and protease inhibitor satisfy some conditions, the uninfected steady state is a unique equilibrium in the feasible region, and the point is globally asymptotically stable. However, if the treatment is not effective enough, then the equilibrium becomes unstable and HIV infection persists. In this case, the other two steady states can be either stable or unstable. By theoretical analyzing, we obtain the results that time delay can affect the stability of the immune-exhausted equilibrium and the infected equilibrium under some conditions. Finally, numerical simulations are carried out to illustrate the main mathematical conclusions. [ABSTRACT FROM AUTHOR]

In this paper, a HTLV-I infection model with CTL immune response is considered. Taking the immune delay as a bifurcation parameter we investigate the global existence of periodic solutions of this model which shows existence of multiple periodic solutions theoretically. [ABSTRACT FROM AUTHOR]

Due to immunological activity, microbial cell wall polysaccharides are defined as ‘biological response modifiers’ (BRM). Cell walls of spent brewer's yeast also have some BRM activity. However, up to date there is no consensus on the use of spent brewer's yeast d -glucan as specific BRM in humans or animals. The aim of this paper is to demonstrate the potential of spent brewer's yeast β - d -glucans as BRM, and drying as an efficient pretreatment to increase β - d -glucan's immunogenic activity. Our results revealed that drying does not change spent brewer's yeast biomass carbohydrate content as well as the chemical structure of purified β - d -glucan. However, drying increased purified β - d -glucan TNF- α induction activity in the murine macrophage model. We presume drying pretreatment enhances purity of extracted β - d -glucan. This is corroborated with FT-IR analyses of the β - d -glucan spectra. Based on our results, we suggest that dry spent brewer's yeast biomass can be used as a cheap source for high-quality β - d -glucan extraction. Drying in combination with carboxylmethylation (CM), endows spent brewer's yeast β - d -glucan with the immunoactivity similar or exceeding that of a well-characterized fungal BRM pleuran. [ABSTRACT FROM AUTHOR]

In this paper, a delay differential equation model of immunotherapy for tumor-immune response is presented. The dynamics that interplays between the three model factors, namely, effector cells, tumor cells and interleukin-2 is studied and the quantitative analysis is performed. We estimate the length of delay to preserve the stability of an equilibrium state of biological significance. The impact of delay in the immunotherapy with interleukin-2, especially, at different antigenicity levels, is discussed, along with the scenarios under which the tumor remission can be prolonged. [ABSTRACT FROM AUTHOR]

In this paper, we consider the combined effects of cytotoxic T lymphocyte (CTL) responses on the competition dynamics of two Simian immunodeficiency virus (SIV) strains model. One of strains concerns a relatively slowly replicating and mildly cytopathic virus in the early infection (SIVMneCL8), the other is faster replicating and more cytopathic virus at later stages of the infection (SIVMne170). It is shown that the global dynamics of the ordinary differential equations can be determined by several threshold parameters, and we prove the global stability of the equilibria by rigorous mathematical analysis. To account for a series of infection mechanism leading to viral production, we incorporate time delays in the infection term. Using the methods of constructing suitable Lyapunov functionals and LaSalle’s invariance principle, we obtain the sufficient conditions for the global attractiveness of infection-free equilibrium with both virus strains going extinct, single-infection equilibrium with one of two virus strains out-competing the other one and the two strains coexisting infection equilibrium. We establish that the intracellular delays can destabilize the single-infection equilibrium leading to Hopf bifurcation and periodic oscillations. We show that introduction of immune responses is responsible for the coexistence of two virus strains and the intracellular delays may alter the two-strain competition results. Numerical simulations are presented to illustrate the theoretical conclusions. [ABSTRACT FROM AUTHOR]

This paper describes a signal enhancement strategy to improve the sensitivity of an antibody-based immunosensor that uses polydiacetylene (PDA) liposomes to detect a target protein (human immunoglobulin E [hIgE]). To achieve ultrasensitive detection, multiple stimuli applied to PDA immunosensor chips offer a signal enhancement method that combines the primary immune reaction between antigen and antibody with the sandwich method of polyclonal antibody (pAb)-conjugated horseradish peroxidase (HRP). In the second step, fluorescence is enhanced by the mechanical pressure from the precipitate formed by enzyme catalysis. In order to detect hIgE, the surface of immobilized PDA liposomes was conjugated with monoclonal antibodies against hIgE, and fluorescence signals were detected after the antigen-antibody reaction. In this step, hIgE concentrations as low as 10ng/mL were detected. Fluorescence signals slightly increased when anti-hIgE pAb-HRP was used as an amplifying agent after primary immunoresponse. After secondary immunoresponse, HRP-catalyzed oxidation of 3,3′-diaminobenzidine produced an insoluble precipitate that strongly stimulated PDA liposomes by their weight and pressure, thereby dramatically increasing the fluorescence signal. Thus, PDA liposome immunosensor could detect hIgE concentrations as low as 0.01ng/mL, representing a 1000-fold increase in sensitivity over the signal generated by the primary immunoresponse. This study indicates that increasing the external mechanical force applied to PDA liposomes by enzyme-catalyzed precipitate formation enhanced the sensitivity of the PDA liposome immunosensor chip. This strategy can be applied to the detection of other biomolecules in experimental or clinical settings where ultrasensitive and highly specific biosensing is required. [ABSTRACT FROM AUTHOR]

This paper deals with the qualitative analysis of a nonlinear model of immune response with special attention to the actions applied by cytokine signals to activate the last one, in the framework of the mathematical kinetic theory for active particles. The content focuses on the early stage of the competition before the onset of proliferation. The analysis gives evidence how parameters and initial conditions influence the asymptotic behaviors of solutions. [ABSTRACT FROM AUTHOR]

It is highly desired to explore the interventions of COVID-19 for early treatment strategies. Such interventions are still under consideration. A model is benchmarked research and comprises target cells, virus infected cells, immune cells, pro-inflammatory cytokines, and, anti-inflammatory cytokine. The interaction of the drug with the inflammatory sub-system is analyzed with the aid of kinetic modeling. The impact of drug therapy on the immune cells is modelled and the computational framework is verified with the aid of numerical simulations. The work includes a significant hypothesis that quantifies the complex dynamics of the infection, by relating it to the effect of the inflammatory syndrome generated by IL-6. In this paper we use the cancer immunoediting process: a dynamic process initiated by cancer cells in response to immune surveillance of the immune system that it can be conceptualized by an alternating movement that balances immune protection with immune evasion. The mechanisms of resistance to immunotherapy seem to broadly overlap with those used by cancers as they undergo immunoediting to evade detection by the immune system. In this process the immune system can both constrain and promote tumour development, which proceeds through three phases termed: (i) Elimination, (ii) Equilibrium, and, (iii) Escape [1]. We can also apply these concepts to viral infection, which, although it is not exactly "immunoediting", has many points in common and helps to understand how it expands into an "untreated" host and can help in understanding the SARS-CoV2 virus infection and treatment model. Unlabelled Image • Drug therapy on immune cells is modelled. • Cytokines storm during SARS-CoV2 infection is examined. • The interaction of drug with the inflammatory sub-system is taken into account. [ABSTRACT FROM AUTHOR]

The efficiency of the promising deterministic dendritic cell algorithm (dDCA) in terms of anomaly detection has been demonstrated in large number of studies. However, the results of these studies also show that the signal calculation phase of dDCA depends on artificial experience, while the algorithm also lacks adaptability. To overcome these limitations, we propose a new approach for anomaly detection based on dDCA, in which numerical differential and immune responses are applied. The numerical differential is introduced to provide a new method of calculating the signal values that is independent of artificial experience. In the immune response method, moreover, the immune nonlinear model is adopted to adjust the weight signal matrix of dDCA. The experimental results show that the proposed algorithm has significant advantages over the compared immune anomaly detection approaches in terms of signal calculation and adaptability. • A dDCA with numerical differentiation and immune response is proposed in this paper. • Numerical differentiation is used for signal extraction. • An immune dynamic model of nonlinear model is used to adjust the weights in dDCA. • Experimental results show that the proposed algorithm achieves a better performance. [ABSTRACT FROM AUTHOR]

Encapsulation of pancreatic islets in alginate-microcapsules is used to reduce or avoid the application of life-long immunosuppression in preventing rejection. Long-term graft function, however, is limited due to varying degrees of host tissue responses against the capsules. Major graft-longevity limiting responses include inflammatory responses provoked by biomaterials and islet-derived danger-associated molecular patterns (DAMPs). This paper reports on a novel strategy for engineering alginate microcapsules presenting immunomodulatory polymer pectin with varying degrees of methyl-esterification (DM) to reduce these host tissue responses. DM18-pectin/alginate microcapsules show a significant decrease of DAMP-induced Toll-Like Receptor-2 mediated immune activation in vitro , and reduce peri-capsular fibrosis in vivo in mice compared to higher DM-pectin/alginate microcapsules and conventional alginate microcapsules. By testing efficacy of DM18-pectin/alginate microcapsules in vivo , we demonstrate that low-DM pectin support long-term survival of xenotransplanted rat islets in diabetic mice. This study provides a novel strategy to attenuate host responses by creating immunomodulatory capsule surfaces that attenuate activation of specific pro-inflammatory immune receptors locally at the transplantation site. [ABSTRACT FROM AUTHOR]

• The biomedical model is employed to track the immune response and the HCMV infection. • The objective of control method is to balance the immune system level. • Using the proposed method, concentration of serum creatinine decreased considerably. • The nonlinear adaptive method guarantees the robustness of the system. • Lyapunov theorem and Barbalat's lemma are used to prove the system's stability. The present paper describes a nonlinear adaptive control method to adjust the drug dose in renal transplant recipients with HCMV-infection. Successful renal transplantation necessitates a reduction in the immune response level, which exposes patients in danger of infectious diseases. Human cytomegalovirus (HCMV) is a common infection among kidney transplantation recipients and is observed in primary and reactivated stages. The primary infection happens when an infectious agent enters the body after an organ transplant, whereas the second is linked to the reactivation by a latent infection. In the present study, the drug dose is considered as the control input for the dynamics of immune response for kidney transplantation and HCMV infection. The control law is aimed to maintain the immune response in a reasonable range and reduce the transplantation rejection risk using drug dosage adjustment. Adaptation law is designed in order to adjust the parameter estimation to overcome uncertainties in model parameters. Taking advantage of the proposed control and adaptation laws, the proposed controller is robust against uncertainties and useful for implementing in different clinical situations. Lyapunov stability theorem is used to prove the asymptotic stability of the closed-loop system, which would guarantee the convergence of the system output to the desired scenario in the presence of different uncertainty levels. Several numerical simulations are presented and discussed to investigate the effectiveness of the proposed control method from mathematical and biological perspectives. [ABSTRACT FROM AUTHOR]

Several researches reported that piscidin members of teleosts owned strong antiparasitic activity. Cryptocaryon irritans , a type of ectoparasite, could infect most of the marine teleosts. Larimichthys crocea could severely suffer from marine white spot disease caused by C. irritans , and their mortality rate was significantly high. Concentrating on this problem, we have done many related works. Piscidin 5 like (termed Lc-P5L) was another piscidin member isolated from a comparative transcriptome of C. irritans -immuned L. crocea. In the paper, quantitative Real-time PCR (qRT-PCR) showed Lc-P5L was upregulated in examined tissues, including gill, head kidney, muscle, liver, spleen and intestine after challenged by C. irritans , the significant upregulation time was in accordance to key developmental stages of C. irritans , which implied different infection stages could result in host immune response. Furthermore, using microscope techniques, we observed theronts or trophonts became weakly motile, cilia became detached, cells were out of shape, membranes eventually lysed in different cell positions and cytoplasmic contents leaked. Laser confocal scanning microscope (LCSM) observed theronts macronucleus grew swell and depolymerized after treated by recombinant Lc-P5L (rLc-P5L). Data suggested rLc-P5L was significantly lethal to C. irritans , and the death state of the parasite incubated with rLc-P5L was remarkably similar to other piscidin members or other antiparasitic peptides (APPs). Thus, these data provided new insights into L. crocea immunity against C. irritans and potential of rLc-P5L as a therapeutic agent against pathogen invasion. • LcP5L was involved in the whole immune response against C. irritans infection. • rLcP5L owned strong antiparasitic activity against theronts. • rLcP5L could cause macronucleus swelling, membrane rupture and contents leakage. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the effect of supplemental camphor on the performance and immune functions of Japanese quail by feeding graded levels (0 (control), 250, 500, 750, 1000, 5000 or 10 000 ppm) of camphor during a 42-day feeding trial. In all, 280 1-day-old quail chicks were randomly assigned into 28 cages of 10 chicks each with separate feeders. The results clearly demonstrated that camphor did not have a significant effect on BW, BW gain, total experimental average daily feed intake, feed conversion ratio, internal organ relative weights and biochemical parameters such as uric acid, albumin, total protein and triglyceride; however, plasma cholesterol concentration was significantly different in a linear manner, in which 500 ppm of camphor resulted in a lower level of cholesterol. Alternatively, greater concentrations of glucose and high-density lipoprotein (HDL) were also found in 5000 and 1000 ppm of camphor groups, respectively. Cellular responses to the phytohaemagglutinin-P and 2,4-dinitro 1-chlorobenzene skin test were not influenced by dietary camphor. Humoral responses to secondary sheep red blood cells, avian influenza virus (AIV) and Newcastle disease virus (NDV) immunisations were positively influenced by camphor supplementation, in which greater secondary response to sheep erythrocytes belonged to 750 and 1000 ppm of camphor groups; whereas, diet supplementation with camphor had no significant effect on lymphoid organ weights and heterophil-to-lymphocyte ratio. The greatest AIV antibody titers were seen in groups, which received 1000 and 5000 ppm of camphor (P<0.05) and the values of NDV antibody titers increased with an increase in the camphor consumption. Furthermore, dietary inclusion of 500 ppm of camphor positively decreased coliform populations in the gastrointestinal tract (GIT). In addition, an increase in lactic acid bacteria was also observed in quails, which were fed on the diets containing 750 ppm camphor. Collectively, these data suggest that as a phytogenic feed additive, camphor may effectively act as a modulator of health status (by increasing glucose and HDL), GIT microbiota and immunological responses of the Japanese quail. [ABSTRACT FROM PUBLISHER]