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Objective: Atopic dermatitis (AD) is an inflammatory skin disease. Naringenin (Nar) possesses an anti-inflammatory property. This paper attempts to discuss the functional mechanism of Nar in AD mice through the Janus kinase 2 (JAK2)/signal transducer and activation of transcription 3 (STAT3) pathway. Methods: Mouse models of DNFB-induced AD were established and treated with Nar, followed by intraperitoneal injection with the JAK2/STAT3 pathway activator Coumermycin A1. Dermatitis severity was scored and the thickness of right ear was measured. The pathological changes in dorsal skin tissues were observed by HE staining. The number of infiltrated mast cells and eosinophilic granulocytes was counted by TB staining. The serum IgE level and levels of TNF-α, IL-6, IFN-γ, IL-12, and IL-5 in dorsal skin tissues were measured by ELISA. The levels of p-JAK2, JAK2, p-STAT3, and STAT3 were determined by Western blot. Results: Nar decreased dermatitis scores and right ear thickness, alleviated skin lesions, and reduced the number of infiltrated mast cells and eosinophilic granulocytes in AD mice. The serum IgE level and levels of TNF-α, IL-6, IFN-γ, IL-12, and IL-5 in dorsal skin tissues of AD mice were diminished after Nar treatment in a dose-dependent manner. Nar inhibited the activation of the JAK2/STAT3 pathway. The activation of the JAK2/STAT3 pathway partially nullified the therapeutic function of Nar on AD mice. Conclusion: Nar protects mice from AD by inhibiting inflammation and promoting immune responses through the inhibition of the JAK2/STAT3 pathway. [ABSTRACT FROM AUTHOR]

Primary antibody deficiencies (PADs) are the most common primary immunodeficiencies and are characterized by a defect in the production of normal amounts of antigen-specific antibodies. PADs represent a heterogeneous spectrum of conditions, ranging from often asymptomatic selective IgA and IgG subclass deficiencies to the severe congenital agammaglobulinemias, in which the antibody production of all immunoglobulin isotypes is severely decreased. Apart from recurrent respiratory tract infections, PADs are associated with a wide range of other clinical complications. This review will describe the pathophysiology, diagnosis, and treatment of the different PADs. [ABSTRACT FROM AUTHOR]

The article provides information on pathogen Listeria monocytogenes. According to a research, such pathogen takes advantage of a facet of its host's immune response and it produces a protein called listeriolysin O (LLO) that injects pores into membranes. This action allows the bacterium to escape from intracellular areas charged with its destruction and to replicate and spread.

We present a Bayesian partial membership model that estimates the associations between an outcome, a small number of latent variables, and multiple observed exposures where the number of latent variables is specified a priori. We assign one observed exposure as the sentinel marker for each latent variable. The model allows non-sentinel exposures to have complete membership in one latent group, or partial membership across two or more latent groups. MCMC sampling is used to determine latent group partial memberships for the non-sentinel exposures, and estimate all model parameters. We compare the performance of our model to competing approaches in a simulation study and apply our model to inflammatory marker data measured in a large mother-child cohort of the Seychelles Child Development Study (SCDS). In simulations, our model estimated model parameters with little bias, adequate coverage, and tighter credible intervals compared to competing approaches. Under our partial membership model with two latent groups, SCDS inflammatory marker classifications generally aligned with the scientific literature. Incorporating additional SCDS inflammatory markers and more latent groups produced similar groupings of markers that also aligned with the literature. Associations between covariates and birth weight were similar across latent variable models and were consistent with earlier work in this SCDS cohort. Supplementary materials accompanying this paper appear online. [ABSTRACT FROM AUTHOR]

In this paper, we propose a general acute myeloid leukemia (AML) model and introduce an immune response and time delays into this model to investigate their effects on the dynamics. Based on the existence, stability and local bifurcation of three types of equilibria, we show that the immune response is a best strategy for the control of the AML on the condition that the rates of proliferation and differentiation of the hematopoietic lineage exceed a threshold. In particular, a powerful immune response leads to a bistability feature meaning there exist the leukemia cells and healthy cells in the bone marrow or only the healthy cells. In addition, we further reveal that the time delays in the feedback regulation and immune response process induce a series of oscillations around the steady state, which shows that the leukemia cells are hardly eliminated. Our work in this paper aims to investigate the complex dynamics of this AML model with the immune response and time delays on the basis of mathematical models and numerical simulations, which may provide a theoretical guidance for the treatments of the AML. [ABSTRACT FROM AUTHOR]

Necroptosis, a programmed form of necrotic cell death, plays critical regulatory roles in the progression and metastatic spread of cancers such as cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC). However, there are few articles systematically analyzing the necroptosis-related long non-coding RNAs (NRlncRNAs) correlated with CESC patients. Both RNA-sequencing and clinical data of CESC patients are downloaded from TCGA database in this study. Pearson correlation analysis, least absolute shrinkage, operator algorithm selection and Cox regression model are employed to screen and create a risk score model of eleven-NRlncRNAs (MIR100HG, LINC00996, SNHG30, LINC02688, HCG15, TUBA3FP, MIAT, DBH-AS1, ERICH6-AS1SCAT1, LINC01702) prognostic. Thereafter, a series of tests are carried out in sequence to evaluate the model for independent prognostic value. Gene set enrichment analytic paper, Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analytic paper make it clear that immune-related signaling pathways are very rich in the high-risk subgroup. Additionally, the prognostic risk score model is correlated to immune cell infiltration, potential immune checkpoint, immune function, immune micro-environmental and m6A-related gene. Mutation frequency in mutated genes and survival probability trend are higher in the low-risk subgroup in most of test cases when compared to the high-risk subgroup. This study constructs a renewed prognostic model of eleven-NRlncRNAs, which may make some contribution to accurately predicting the prognosis and the immune response from CESC patients, and improve the recognition of CESC patients and optimize customized treatment regimens to some extent. [ABSTRACT FROM AUTHOR]

Time of day affects how well the immune system responds to viral or bacterial infections. While it is well known that the immune system is regulated by the circadian clock, the dynamic origin of time-of-day-dependent immunity remains unclear. In this paper, we studied the circadian control of immune response upon infection of influenza A virus through mathematical modeling. Dynamic simulation analyses revealed that the time-of-day-dependent immunity was rooted in the relative phase between the circadian clock and the pulse of viral infection. The relative phase, which depends on the time the infection occurs, plays a crucial role in the immune response. It can drive the immune system to one of two distinct bistable states, a high inflammatory state with a higher mortality rate or a safe state characterized by low inflammation. The mechanism we found here also explained why the same species infected by different viruses has different time-of-day-dependent immunities. Further, the time-of-day-dependent immunity was found to be abolished when the immune system was regulated by an impaired circadian clock with decreased oscillation amplitude or without oscillations. [ABSTRACT FROM AUTHOR]

Immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies are important biomarkers used for the diagnosis and screening of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in both symptomatic and asymptomatic individuals. These antibodies are highly specific to the spike (S) and nucleocapsid (N) proteins of the SARS-CoV-2 virus. This paper outlines the development steps of a novel hybrid (vertical-lateral-vertical) flow assay in the form of a finger-stick point-of-care device, similar to an adhesive bandage, designed for the timely detection and screening of IgM and IgG immune responses to SARS-CoV-2 infections. The assay, comprising a vertically stacked plasma/serum separation membrane, conjugate pad, and detection (readout) zone, utilizes gold nanoparticles (AuNPs) conjugated with SARS-CoV-2 S and N proteins to effectively capture IgM and IgG antibodies from a pinprick (~15 µL) of blood in just one step and provides results of no immune IgM−/IgG−, early immune IgM+/IgG−, active immune IgM+/IgG+ or immune IgM−/IgG+ in a short amount of time (minutes). The adhesive bandage-like construction is an example of the design of rapid, low-cost, disposable, and easy-to-use tests for large-scale detection and screening in households. Furthermore, the bandage can be easily adjusted and optimized to detect different viral infections as they arise by simply selecting appropriate antigens related to pandemics and outbreaks. [ABSTRACT FROM AUTHOR]

Human papillomavirus belongs to papovaviridae family papillomavirus A, a spherical deoxyribonucleic acid (DNA) virus, which can cause the proliferation of squamous epithelial cells of human skin or mucous membranes. With the rapid increase in the incidence of condyloma acuminatum among STDs and the increase in diseases caused by HPV infection, HPV infection has seriously endangered human health. In this paper, the in vitro detection of HPV E1 protein was realized using AgNCs-dsDNA. And through the test of this detection method, we calculated that the detection limit of this method is 0.886 nM. Compared with other methods for detecting E1 protein in vitro, this method has high sensitivity and simple operation. In addition, the detection method also has good anti-interference and selectivity, and can realize the detection of E1 in serum samples. The transfection efficiency of BLV-miR-B4-3p mimics at different time points was determined by quantitative real-time PCR (qPCR); the transcriptome sequencing of lymphocytes transfected with different concentrations of BLV-miR-B4-3p mimics was performed, and differential gene clustering was performed on the sequencing results. And the BLV-miR-B4-3p target gene prediction and transcriptome analysis results were verified by qPCR. The effects of BLV-miR-B4-3p on the transcriptional levels of immune-related cytokines in human lymphocytes were analyzed. Transcriptome sequencing analysis showed that after BLV-miR-B4-3p entered lymphocytes, a total of 556 differentially expressed genes were obtained. GO enrichment and KEGG analysis results showed that BLV-miR-B4-3p could independently activate influenza. The signaling pathway ultimately affects the body's immune system process, stress response, defense response, immune response, and other biological processes. After BLV-miR-B4-3p enters lymphocytes, it will lead to abnormal lymphocyte immune function, including the mRNA expression of TNF-α in Th1 cytokines which was significantly increased (P < 0.05), and the expression of IL-10 in Th2 cytokines was significantly increased (P < 0.05). The mRNA expression was significantly decreased (P < 0.05), and the mRNA expression of IL-27 was significantly increased (P < 0.001), which did not affect the mRNA expression of lymphocyte proliferation and activation-related regulators. The tumor suppressor breast cancer 1 (BRCA1) and antimicrobial peptide CAMP were significantly increased, and decreased (P < 0.001), and the expression of pro-apoptotic factor Caspase9 showed a significant downward trend (P < 0.05). [ABSTRACT FROM AUTHOR]

Background: Circadian rhythm is characterised by daily variations in biological activity to align with the light and dark cycle. These diurnal variations, in turn, influence physiological functions such as blood pressure, temperature, and sleep–wake cycle. Though it is well established that the circadian pathway is linked to pro-inflammatory responses and circulating immune cells, its association with infectious diseases is widely unknown. Objective: This comprehensive review aims to describe the association between circadian rhythm and host immune response to various kinds of infection. Methods: We conducted a literature search in databases Pubmed/Medline and Science direct. Our paper includes a comprehensive analysis of findings from articles in English which was related to our hypothesis. Findings: Molecular clocks determine circadian rhythm disruption in response to infection, influencing the host's response toward infection. Moreover, there is a complex interplay with intrinsic oscillators of pathogens and the influence of specific infectious processes on the CLOCK: BMAL1 pathway. Such mechanisms vary for bacterial and viral infections, both well studied in the literature. However, less is known about the association of parasitic infections and fungal pathogens with circadian rhythm modulation. Conclusion: It is shown that bidirectional relationships exist between circadian rhythm disruption and infectious process, which contains interplay between the host's and pathogens' circadian oscillator, immune response, and the influence of specific infectious. Further studies exploring the modulations of circadian rhythm and immunity can offer novel explanations of different susceptibilities to infection and can lead to therapeutic avenues in circadian immune modulation of infectious diseases. [ABSTRACT FROM AUTHOR]

In this paper, we propose a general viral infection model to incorporate two infection modes (virus-to-cell mode and cell-to-cell mode), the CTL immune response, and the distributed intracellular delays during the processes of viral infection, viral production, and CTLs recruitment. We investigate the existence, the uniqueness, and the global stability of three equilibria: infection-free equilibrium E 0 , immune-inactivated equilibrium E 1 and immune-activated equilibrium E 2 , respectively. We prove that the viral dynamics are determined by two threshold parameters: the basic reproduction number for infection R 0 and the basic reproduction number for immune response R IM . We also numerically explore the viral dynamics beyond stability. We use bifurcation diagrams to show that increasing the delay in CTL immune cell recruitment can induce a switch in viral load from a stable constant level to sustained oscillations, and then back to a stable equilibrium. We also compare the contributions of the two infection modes to the total infection level and identify the key parameters that would affect the percentages of virus-to-cell infection and cell-to-cell infection. Finally, we explore how Filippov control can be applied in antiretroviral therapy to reduce the viral loads. [ABSTRACT FROM AUTHOR]

HIV (human immunodeficiency virus) is a dangerous virus that constantly diminishes an individual's immune system by explicitly targeting CD4 cells, which are the body's key protectors against disease by obstructing them to make duplicates of themselves. If left untreated, it can lead to AIDS (acquired immunodeficiency syndrome). The Treatment involves antiretroviral therapy which maintains the immunity to a specific level and thus helps in suppressing the virus replication. This paper emphasizes on the development of the model involving healthy and infected population, virus population, antibodies and CTL cells. The investigation encapsulates the local stability based on thresholds followed by the local bifurcation analysis based on β 1 and R 0 . The global stability analysis is done the using Graph- theoretic approach. Further the optimal control problem is discussed using Linear feedback control method which aims to reduce the viral load by keeping antibodies to a certain level. Numerical discussion includes surface plots of the thresholds based on various parameters, graphs showing the comparison between without control and with control especially for the virus population, infected population and antibodies which are our target. Finally, we have also shown the curve-fitting for our data using optimized Nedlar-Mean algorithm. [ABSTRACT FROM AUTHOR]

Immune responses have a crucial role to play against SARS-CoV-2 virus as the adaptive and innate immune systems of the human body help restoring the body to a healthy stage by annihilating this deadly viral infection. Cytokines also play a significant role in modulating a balance between innate and adaptive immune responses but excess of it can have a detrimental affect on critically ill patients. Therefore, this paper is a novel attempt to formulate a within-host mathematical model showing the impact of cytokines storm on healthy cells. The dynamics of the system is analysed which involves basic reproduction number, steady state solutions and global dynamics for disease-free point and endemic equilibrium using geometric approach. Further, an optimal control problem is discussed considering immunomodulatory therapy (targeting cytokines signaling) as control using linear feedback control method to increase the level of healthy cells, which provides vitality for our system. Through numerical simulations, analytic solutions are validated followed by the curve-fit for the cytokines using real data and an optimization algorithm for optimal fit. Finally, sensitivity analysis for the basic reproduction number and the rate of change of healthy cells using Latin Hypercube Sampling method (LHS) is performed. Our finding suggests that immunomodulatory therapy (tocilizumab) can act as a key component to control cytokines storm for critically ill patients to restore the body to a healthy state. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the selenium (Se) behavior when used as an endodontic dressing in teeth with pulp necrosis. Additionally, its effects was also compared with the calcium hydroxide (C.H.), which is used globally as a root canal dressing, and the combination of the C.H. with Se (C.H. + Se). Materials and methods: The sample consisted of 60 patients requiring endodontic treatment who were divided into groups, i.e., without intracanal medication (empty) and with medications as follows: selenium (Se), calcium hydroxide (C.H.), and calcium hydroxide + selenium (C.H. + Se) (n = 15). After the coronary opening, three absorbent paper points were placed in the RCS and maintained for 2 min for microbial evaluation. Following the cleaning and shaping procedures, new paper points were introduced into the root canal system, passing passively through the root apex (2 mm) into the periapical tissues for 2 min, for immune evaluation. The collections were performed again 15 days later. Real-time PCR quantified the expression of the prokaryotic 16S ribosomal RNA. The 16S mRNA was evaluated before the cleaning and shaping procedures and 15 days later in the groups treated with or without medication. Results: A significant reduction in the microbial load was observed only in the groups that received endodontic dressing (p < 0.05). The cytokines IFN-γ, TNF-α, IL-1α, IL-17A, IL-10, IL-6 and MCP-1, were also quantified by real-time PCR. There was an increase in the gene expression level of the cytokines (T15) TNF-α and IL-10 in the C.H. group compared to the other groups (p < 0.05). The IFN-γ mRNA expression was reduced in the groups treated with the medications (Se, C.H., and C.H. + Se). Conclusions: The findings of the present study indicate that in the case of treatment over multiple sessions, the use of root canal dressing is essential to avoid the root canal system (RCS) microbial recolonization. Selenium potentiated the effects of calcium hydroxide inducing an anti-inflammatory response in periapical tissues. Clinical relevance: Se is a mineral essential for the formation of the amino acid selenocysteine, which is directly involved in the maintenance of the immune response. Selenium has been widely used in the medical field in the treatment of cancer, as an activator of bone metabolism, and as a stimulator of the immune system. In this study, it was shown that the incorporation of Se, whether as intracanal medication alone or in conjunction with other medications, may potentiate periapical tissue repair after RCS cleaning and shaping procedures. [ABSTRACT FROM AUTHOR]

In this paper, assuming the certain variable satisfies the Ornstein–Uhlenbeck process, we formulate a stochastic within-host dengue model with immune response to obtain further understanding of the transmission dynamics of dengue fever. Then we analyze the dynamical properties of the stochastic system in detail, including the existence and uniqueness of the global solution, the existence of a stationary distribution, and the extinction of infected monocytes and free viruses. In particular, it is worth revealing that we get the specific form of covariance matrix in its probability density around the quasi-endemic equilibrium of the stochastic system. Finally, numerical illustrative examples are depicted to confirm our theoretical findings. [ABSTRACT FROM AUTHOR]

Macrophage receptor with collagen structure (MARCO) is a member of scavenger receptor class A (SR-A) and shares structural and functional similarities with SR-A1. In recent years, many studies have shown that MARCO can trigger an immune response and has therapeutic potential as a target for immunotherapy. Studies have shown that alterations in MARCO expression following pathogen infection cause changes in the functions of innate and adaptive immune cells, including macrophages, dendritic cells, B cells, and T cells, affecting the body's immune response to invading pathogens; thus, MARCO plays a crucial role in triggering the immune response, bridging innate and adaptive immunity, and eliminating pathogens. This paper is a comprehensive summary of the recent research on MARCO. This review focuses on the multiple functions of MARCO, including adhesion, migration, phagocytosis, and cytokine secretion with special emphasis on the complex interactions between MARCO and various types of cells involved in the immune response, as well as possible immune-related mechanisms. In summary, in this review, we discuss the structure and function of MARCO and its role in the immune response and highlight the therapeutic potential of MARCO as a target for immunotherapy. We hope that this review provides a theoretical basis for future research on MARCO. [ABSTRACT FROM AUTHOR]

Background: CT-P43 is a candidate ustekinumab biosimilar in clinical development. Objectives: This paper aims to demonstrate equivalent efficacy of CT-P43 to originator ustekinumab in adults with moderate to severe plaque psoriasis. Methods: This double-blind, phase III trial randomised patients (1:1) to receive subcutaneous CT-P43 or originator ustekinumab (45/90 mg for patients with baseline body weight ≤ 100 kg/> 100 kg) at week 0 and week 4 in Treatment Period I. Prior to week 16 dosing in Treatment Period II, patients receiving originator ustekinumab were re-randomised (1:1) to continue originator ustekinumab or switch to CT-P43; patients initially randomised to CT-P43 continued receiving CT-P43 (at weeks 16, 28 and 40). The primary endpoint of the trial was mean per cent improvement from baseline in Psoriasis Area Severity Index (PASI) score at week 12. Equivalence was concluded if confidence intervals (CIs) for the estimate of treatment difference were within pre-defined equivalence margins: ± 10% [90% CI; modified intent-to-treat set; Food and Drug Administration (FDA) approach] or ± 15% [95% CI; full analysis set for patients only receiving 45 mg doses in Treatment Period I; European Medicines Agency (EMA) approach]. Additional efficacy, pharmacokinetic, safety and immunogenicity endpoints were evaluated through week 52. Results to week 28 are reported here. Results: In Treatment Period I, 509 patients were randomised (CT-P43: N = 256; originator ustekinumab: N = 253). The mean per cent improvement in PASI score at week12 was 77.93% and 75.89% for CT-P43 and originator ustekinumab, respectively (FDA approach); per the EMA approach, corresponding values were 78.26% and 77.33%. Estimated treatment differences were 2.05 (90% CI −0.23, 4.32) and 0.94 (95% CI −2.29, 4.16); equivalence was achieved for both sets of assumptions. Further efficacy parameters and pharmacokinetic, safety and immunogenicity outcomes were comparable between treatment groups, including after switching from originator ustekinumab to CT-P43. Conclusions: CT-P43 demonstrated equivalent efficacy to originator ustekinumab in patients with moderate to severe plaque psoriasis, with comparable pharmacokinetic, safety and immunogenicity profiles. Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT04673786; date of registration: 17 December, 2020 [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]

Bisphenol (BP)A is an endocrine disruptor (ED) widely used in thermal papers. Regulatory restrictions have been established to prevent risks for human health, leading to BPA substitution by structural analogues, like BPS and BPF. We previously demonstrated that oral perinatal exposure to BPA had long-term consequences on immune responses later in life. It appears now essential to enhance our understanding on immune impact of different routes of BP exposure. In this study, we aimed at comparing the impact of mother dermal exposure to BPs on offspring immune system at adulthood. Gravid mice were dermally exposed to BPA, BPS or BPF at 5 or 50 μg/kg of body weight (BW)/day (d) from gestation day 15 to weaning of pups at post-natal day (PND)21. In offspring, BPs dermal impregnation of mothers led to adverse effects on immune response at intestinal and systemic levels that was dependent on the BP, the dose and offspring sex. These findings provide, for the first time, results on long-term consequences of dermal perinatal BPs exposure on immune responses in offspring. This work warns that it is mandatory to consider immune markers, dose exposure as well as sex in risk assessment associated with new BPA's alternatives. [ABSTRACT FROM AUTHOR]

In this paper, we construct a general four-dimensional delayed HIV infection model with virus-to-cell infection, cell-to-cell transmission, CTL immune response and parameter perturbations. By substitution, the four-dimensional delayed stochastic differential equations can be transformed into a degenerate eight-dimensional stochastic differential equations. The existence of the global positive solution of the system is obtained rigorously. By constructing appropriate Lyapunov functions, the existence of a stationary Markov process is derived when the stochastic reproduction number R 0 s is greater than one. Finally, we investigate the effects of noise level and the cell-to-cell transmission on the dynamic behavior of the model. Our model is a general model of the existing stochastic virus infection model, and the theoretical results improve and generalize the existing conclusion. [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]

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]

The cellular adaptive immune response to influenza has been analyzed through several recent mathematical models. In particular, Zarnitsyna et al. (Front Immunol 7:1–9, 2016) show how central memory CD8+ T cells reach a plateau after repeated infections, and analyze their role in the immune response to further challenges. In this paper, we further investigate the theoretical features of that model by extracting from the infection dynamics a discrete map that describes the build-up of memory cells. Furthermore, we show how the model by Zarnitsyna et al. (Front Immunol 7:1–9, 2016) can be viewed as a fast-scale approximation of a model allowing for recruitment of target epithelial cells. Finally, we analyze which components of the model are essential to understand the progressive build-up of immune memory. This is performed through the analysis of simplified versions of the model that include some components only of immune response. The analysis performed may also provide a theoretical framework for understanding the conditions under which two-dose vaccination strategies can be helpful. [ABSTRACT FROM AUTHOR]

HIV and HTLV-I are two retroviruses that infect the CD 4 + T cells. HIV causes acquired immunodeficiency syndrome, while HTLV-I is the causative agent for adult T-cell leukemia and HTLV-I-associated myelopathy/tropical spastic paraparesis. It is not surprising that a mono-infected patient with one of these viruses can be exposure to co-infect with the other virus since they share the same way of transmissions between individuals, through direct contact with certain contaminated body fluids. Mathematical modeling and analysis of HIV and HTLV-I mono-infections have received considerable attention during the last decades. However, the dynamics of HIV/HTLV-I co-infection has not been formulated. In the present paper, we formulate a new HIV/HTLV-I co-infection model with cytotoxic T lymphocytes (CTLs) immune response. The model describes the interaction between susceptible CD 4 + T cells, HIV-infected cells, Tax-expressing HTLV-infected cells, free HIV particles, HIV-specific CTLs and HTLV-specific CTLs. The HIV can spread by virus-to-cell and cell-to-cell transmissions, while the HTLV-I can only spread via cell-to-cell transmission. The well-posedness of the model is established by showing that the solutions of the model are nonnegative and bounded. We derive the threshold parameters which govern the existence and stability of all equilibria of the model. We prove the global asymptotic stability of all equilibria by utilizing Lyapunov function and applying Lyapunov–LaSalle asymptotic stability theorem. We present numerical simulations to illustrate the effectiveness of our main results. In addition, we discuss the effect of HTLV-I infection on the HIV-infected patients and vice versa. [ABSTRACT FROM AUTHOR]

The development of preventive vaccines became the first order task in the COVID-19 pandemic caused by SARS-CoV-2. This paper reports the construction of the pVAX-RBD plasmid containing the Receptor-Binding Domain (RBD) of the S protein and a unique signal sequence 176 which promotes target protein secretion into the extracellular space thereby increasing the efficiency of humoral immune response activation. A polyglucine-spermidine conjugate (PGS) was used to deliver pVAX-RBD into the cells. The comparative immunogenicity study of the naked pVAX-RBD and pVAX-RBD enclosed in the PGS envelope showed that the latter was more efficient in inducing an immune response in the immunized mice. In particular, RBD-specific antibody titers were shown in ELISA to be no higher than 1 : 1000 in the animals from the pVAX-RBD group and 1 : 42 000, in the pVAX-RBD-PGS group. The pVAX-RBD‒PGS construct effectively induced cellular immune response. Using ELISpot, it has been demonstrated that splenocytes obtained from the immunized animals effectively produced INF-γ in response to stimulation with the S protein-derived peptide pool. The results suggest that the polyglucine-spermidine conjugate-enveloped pVAX-RBD construct may be considered as a promising DNA vaccine against COVID-19. [ABSTRACT FROM AUTHOR]

Fungi are cells found as commensal residents, on the skin, and on mucosal surfaces of the human body, including the digestive track and urogenital track, but some species are pathogenic. Fungal infection may spread into deep-seated organs causing life-threatening infection, especially in immune-compromised individuals. Effective defense against fungal infection requires a coordinated response by the innate and adaptive immune systems. In the present paper we introduce a simple mathematical model of immune response to fungal infection consisting of three partial differential equations, for the populations of fungi (F), neutrophils (N) and cytotoxic T cells (T), taking N and T to represent, respectively, the innate and adaptive immune cells. We denote by λ F the aggressive proliferation rate of the fungi, by η and ζ the killing rates of fungi by neutrophils and T cells, and by N 0 and T 0 the immune strengths, respectively, of N and T of an infected individual. We take the expression I = η N 0 + ζ T 0 - λ F to represent the coordinated defense of the immune system against fungal infection. We use mathematical analysis to prove the following: If I > 0 , then the infection is eventually stopped, and F → 0 as t → ∞ ; and (ii) if I < 0 then the infection cannot be stopped and F converges to some positive constant as t → ∞ . Treatments of fungal infection include anti-fungal agents and immunotherapy drugs, and both cause the parameter I to increase. [ABSTRACT FROM AUTHOR]

Heat stress is one of the greatest challenges for the global livestock industries as increased environmental temperature and humidity compromises animal production during summer leading to devastating economic consequences. Over the last 30 years, significant developments have been achieved in cooling and provision of shade and shelter to mitigate heat stress reducing some of the losses associated with heat stress in farm animals. However, the recent increase in the incidence of heat waves which are also becoming more severe and lasting longer, due to climate change, further accentuates the problem of heat stress. Economic losses associated with heat stress are both direct due to loss in production and animal life, and indirect due to poorer quality products as a result of poor animal health and welfare. Animal health is affected due to impaired immune responses and increased reactive oxygen species production and/or deficiency of antioxidants during heat stress leading to an imbalance between oxidant and antioxidants and resultant oxidative stress. Research over the last 20 years has achieved partial success in understanding the intricacies of heat stress impacts on oxidative stress and immune responses and developing interventions to ameliorate impacts of heat stress, improving immune responses and farm animal health. This paper reviews the body of knowledge on heat stress impacts on immune response in farm animals. The impacts of heat stress on both cell-mediated and humoral immune responses have been discussed identifying the shift in immune response from cell-mediated towards humoral response, thereby weakening the immune status of the animal. Both species and breed differences have been identified as influencing how heat stress impacts the immune status of farm animals. In addition, crosstalk signaling between the immune system and oxidative stress has been considered and the role of antioxidants as potential nutritional strategies to mitigate heat stress has been discussed. [ABSTRACT FROM AUTHOR]

When microorganisms invade a host, the innate immune system first recognizes the pathogen-associated molecular patterns of these microorganisms through pattern recognition receptors (PRRs). Toll-like receptors (TLRs) are known transmembrane PRRs existing in both invertebrates and vertebrates. Upon ligand recognition, TLRs initiate a cascade of signaling events; promote the pro-inflammatory cytokine, type I interferon, and chemokine expression; and play an essential role in the modulation of the host's innate and adaptive immunity. Therefore, it is of great significance to improve our understanding of antimicrobial immune responses by studying the role of TLRs and their signal molecules in the host's defense against invading microbes. This paper aims to summarize the specificity of TLRs in recognition of conserved microbial components, such as lipoprotein, lipopolysaccharide, flagella, endosomal nucleic acids, and other bioactive metabolites derived from microbes. This set of interactions helps to elucidate the immunomodulatory effect of TLRs and the signal transduction changes involved in the infectious process and provide a novel therapeutic strategy to combat microbial infections. [ABSTRACT FROM AUTHOR]

Biologic agents (BA) are able to induce an adaptive immune response in a proportion of exposed patients with the onset of anti-drug antibodies (ADA), which are usually responsible for hypersensitivity reactions (HR). Drug desensitization (DD) for BA allows transient clinical tolerance to the drug in reactive patients. The paper aimed to analyse the modification of drug-specific immune responses along DD in two patients with previous ADA-mediated HR (anaphylaxis) to rituximab and tocilizumab. The in vivo and in vitro assays of humoral and cellular response to drugs were carried out in a longitudinal manner throughout the DD cycles. We observed a progressive decrease of the pre-procedure ADA titer with negativization during the DD cycles in both patients. The monitoring of the drug-specific effector cell response showed the decrease in the BA-induced proliferation, while T cell response to unrelated antigens resulted unmodified along the DD cycles. Lastly, the increase of circulating drug-specific Treg cells mainly producing IL-35 were shown during the DD treatment. This study provides evidence that DD treatment to two BA inhibits humoral and cellular anti-drug response by increasing regulatory T cells and cytokines in an antigen-restricted manner. These modifications could contribute to the safety of the procedure. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

In this paper, the dynamical behaviors for a five-dimensional virus infection model with diffusion and two delays which describes the interactions of antibody, cytotoxic T-lymphocyte (CTL) immune responses and a general incidence function are investigated. The reproduction numbers for virus infection, antibody immune response, CTL immune response, CTL immune competition and antibody immune competition, respectively, are calculated. By using the Lyapunov functionals and linearization methods, the threshold conditions on the global stability of the equilibria for infection-free, immune-free, antibody response, CTL response and antibody and CTL responses, respectively, are established if the space is assumed as homogeneous. When the space is inhomogeneous, the effects of diffusion, intracellular delay and production delay are obtained by the numerical simulations. [ABSTRACT FROM AUTHOR]

Trichinella spiralis, the main pathogen of trichinosis, infects a wide range of mammalian hosts and is one of the most widespread parasites worldwide. For parasites, glycolysis is the most important way to generate energy. Previous studies showed that some enzymes involved in the glycolytic pathway play roles in regulation the host immunity. In this paper, enolase from T. spiralis was cloned and the protective potentials were studied. One hundred and sixty ICR mice were divided into four groups and vaccinated with recombinant enolase (pET-ENO), eukaryotic recombinant plasmid encoding enolase (pVAX1- ENO) and negative controls (pVAX1 and PBS), respectively. Two weeks after the second immunization, each mouse was challenged orally with 200 muscle larvae (MLs) of T. spiralis. Results showed that mice vaccinated with pET-ENO and pVAX1-ENO induced specific antibodies of IgG, IgA, IgM, but no IgE. Subclasses of IgG antibodies showed that mice immunized with recombinant protein and recombinant plasmids induced a Th1/Th2 immune response. Concentrations of serum cytokines were detected and showed significant increase of IFN-γ, IL-4 and TGFβ1, while IL-17 in each group was not significantly different. Flow cytometric analysis showed significant increase of CD4+ and CD8+ T lymphocytes in the groups immunized with recombinant protein and recombinant plasmids. Challenge infection demonstrated that immunized groups had a reduced number of worm burdens. The reductions of larvae per gram muscle (LPG) in pET-ENO and pVAX1-ENO group were 17.7% and 15.8% when compared with PBS control. [ABSTRACT FROM AUTHOR]

Cell migration, known as an orchestrated movement of cells, is crucially important for wound healing, tumor growth, immune response as well as other biomedical processes. This paper presents a cell-based model to describe cell migration in non-isotropic fibrin networks around pancreatic tumor islets. This migration is determined by the mechanical strain energy density as well as cytokines-driven chemotaxis. Cell displacement is modeled by solving a large system of ordinary stochastic differential equations where the stochastic parts result from random walk. The stochastic differential equations are solved by the use of the classical Euler-Maruyama method. In this paper, the influence of anisotropic stromal extracellular matrix in pancreatic tumor islets on T-lymphocytes migration in different immune systems is investigated. As a result, tumor peripheral stromal extracellular matrix impedes the immune response of T-lymphocytes through changing direction of their migration. [ABSTRACT FROM AUTHOR]

The concept of an intelligent manufacturing system is proposed and described based on a comparison of manufacturing and biological organism systems. To promptly eliminate uncertain disturbances produced during the intelligent manufacturing system's operation, an immune monitoring model for an intelligent manufacturing system is proposed that is analogous to a biological immune system mechanism. The implementation of immune recognition, assessment, learning, memory, and control regulation in response to abnormal disturbance factors is investigated. The system's immune evaluation model based on the gray correlation analysis method is carefully analyzed. A neural network-based immune response method is used to deal with the disturbance. Finally, the paper shows how the effectiveness of the proposed method was verified experimentally through a simulation. [ABSTRACT FROM AUTHOR]

Delayed models are a better representation of the nature of HIV. In the present paper, a multi-delayed model of HIV with combination drug therapy has been analysed. Effect of the immune response in the form of effector cell response has also been included to make the model more justified. The threshold properties related with the basic reproduction number R0 have been discussed. The local and global properties of the model have been analysed. Extensive numerical simulations have been performed to show the impact of highly effective drug on the concentration of virus. The numerical simulations and the result proved has led to the conclusion that a highly effective drug when combined with a less effective drug, can very efficiently bring down the viral load to undetectable levels. [ABSTRACT FROM AUTHOR]

An interesting inference drawn by some COVID-19 epidemiological models is that there exists a proportion of the population who are not susceptible to infection—even at the start of the current pandemic. This paper introduces a model of the immune response to a virus. This is based upon the same sort of mean-field dynamics as used in epidemiology. However, in place of the location, clinical status, and other attributes of people in an epidemiological model, we consider the state of a virus, B and T-lymphocytes, and the antibodies they generate. Our aim is to formalise some key hypotheses as to the mechanism of resistance. We present a series of simple simulations illustrating changes to the dynamics of the immune response under these hypotheses. These include attenuated viral cell entry, pre-existing cross-reactive humoral (antibody-mediated) immunity, and enhanced T-cell dependent immunity. Finally, we illustrate the potential application of this sort of model by illustrating variational inversion (using simulated data) of this model to illustrate its use in testing hypotheses. In principle, this furnishes a fast and efficient immunological assay—based on sequential serology—that provides a (1) quantitative measure of latent immunological responses and (2) a Bayes optimal classification of the different kinds of immunological response (c.f., glucose tolerance tests used to test for insulin resistance). This may be especially useful in assessing SARS-CoV-2 vaccines. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed at summarizing evidence about effects of psycho-behavioral interventions (PBIs) on immune responses among cancer patients and analyzing quality of published studies so as to inform future researches. Methods: Literature retrieval utilized both highly inclusive algorithms searching randomized controlled studies published in English and Chinese and manual searching of eligible studies from references of relevant review papers. Two researchers examined the articles selected separately and extracted the information using a pre-designed form for soliciting data about the trials (e.g., sample size, disease status, intervention, immune responses) and quality ratings of the studies. Both narrative descriptions and meta-analysis (via Review manager 5) were used synthesizing the effects of PBIs on immune responses among cancer patients and state of art of the researches in this area. Results: Seventy-six RCTs met inclusion criteria. PBIs implemented were divided into three major categories including psychological state adjustment, physical activity and dietary modification. Immune indicators measured included CD4+ cells, CD8+ cells, CD4/CDC8+ ratio, CD3+ cells, NK cell activity, etc. Effects of PBIs on immune responses documented in individual papers were mixed and pooled analysis of CD4+ cells, CD4+/CD8+ ratio, CD3+ cells, NKCA, IgG, IgM and IL-2 showed modest effects. However, there were huge discrepancies in intervention effects between studies published in English and Chinese and the results should be interpreted with caution. Besides, most studies suffer from some quality flaws concerning blinding, randomization procedures, compliance, attrition and intention-to-treat analyses, etc. Conclusions: Although there are considerable evidences of PBI effects on some immune indicators, the effect sizes are modest and it is still premature to conclude whether PBIs have effects on immune functions among cancer patients. There is a clear need for much more rigorous efforts in this area and future researches should pay particular attention to intervention dose and focus, sample size and comparable immune measures. [ABSTRACT FROM AUTHOR]

This paper proposes a novel binary particle swarm optimization algorithm (called IRBPSO) to address high-dimensional knapsack problems in dynamic environments (DKPs). The IRBPSO integrates an immune-based response strategy into the basic binary particle swarm optimization algorithm for improving the quantity of evolutional particles in high-dimensional decision space. In order to enhance the convergence speed of the IRBPSO in the current environment, the particles with high fitness values are cloned and mutated. In addition, an external archive is designed to store the elite from the current generation. To maintain the diversity of elites in the external archive, the elite of current generation will replace the worst one in the external archive if and only if it differs from any of the existing particles in the external archive based on the Hamming distance measurement when the archive is due to update. In this way, the external archive can store diversiform elites for previous environments as much as possible, and so as to the stored elites are utilized to transfer historical information to new environment for assisting to solve the new optimization problem. Moreover, the environmental reaction scheme is also investigated in order to improve the ability of adapting to different kinds of dynamic environments. Experimental results on a series of DKPs with different randomly generated data sets indicate that the IRBPSO can faster track the changing environments and manifest superior statistical performance, when compared with peer optimization algorithms. [ABSTRACT FROM AUTHOR]

Neurodegeneration is a pathological condition that predominantly affects neurons. It represents a large spectrum of disorders with heterogeneous symptoms and distinct clinical features. In addition to the devastating effects it can have on the affected individual, it constitutes a heavy burden to the society in terms of health care costs. Although the exact cause of neurodegeneration is not known, there are plenty of evidences supporting the notion that the immune system is strongly associated with various forms of neurodegenerative diseases. Given the numerous functions of immune cells, a change in their expression can either be beneficial or deleterious to the host. A better understanding of the molecular and cellular processes in neurodegeneration is therefore needed. This could facilitate the development of new therapeutic targets and provide effective means to dampen the progression of neurodegenerative disorders. The overarching aim of this paper is to provide an overview of the roles that the innate and adaptive immune systems play in the central nervous system, and to discuss their beneficial or detrimental effects during neurodegeneration. This paper also critically examines the contribution of immune and inflammatory-mediated responses in the development of neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and amyloid lateral sclerosis by illustrating key findings from animal and human studies. [ABSTRACT FROM AUTHOR]

Background: Immunoglobulins (IG) are widely used for the treatment of a variety of immune-mediated diseases. The exact mechanism of action remains unknown, but IG modulate the expression and function of Fc receptors, interfere with complement activation and production of cytokines, neutralize pathogenic autoantibodies, and affect the activation and effector functions of B and T lymphocytes. Immunoglobulins are usually delivered intravenously, and are effective in ameliorating motor symptoms, and/or preventing disease progression in immune-mediated neuropathies, including Guillain–Barré syndrome and chronic inflammatory demyelinating polyneuropathy. Objective: The aim of this systematic review and meta-analysis was to study the potential of IG for the treatment of painful peripheral neuropathy (PPN). The outcome of interest was the percentage of patients with PPN who achieved pain relief following IG administration. Methods: We performed a systematic literature search on March 17, 2022, in the PubMed database without any publication date restrictions. We also looked for unpublished or ongoing trials in clinicaltrials.org. Pain reduction following IG treatment had to be within the aims (primary or secondary). Results: The aforementioned literature search strategy revealed five studies (two open-label, three randomized placebo-controlled) eligible to be included. The pooled estimate of the percentage of patients with PPN who received immunoglobulins and reported pain relief was found to be 65% (95% CI 58–71%). The likelihood of achieving pain relief with immunoglobulin treatment was 2.9 times higher (95% CI 1.6–5.2) compared to placebo (p = 0.0003). Conclusion: The use of IG for the treatment of pain due to peripheral neuropathy has a potential therapeutic benefit. Further studies across patients with different types of painful peripheral neuropathy are needed to better characterize this effect. Registration number on PROSPERO: CRD42022319614. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

Annual administration and reformulation of influenza vaccines is required for protection against seasonal infections. However, the induction of strong and long-lasting T cells is critical to reach broad and potentially lifelong antiviral immunity. The NLRP3 inflammasome and its product interleukin-1β (IL-1β) are pivotal mediators of cellular immune responses to influenza, yet, overactivation of these systems leads to side effects, which hamper clinical applications. Here, we present a bypass around these toxicities by targeting the activity of IL-1β to CD8+ T cells. Using this approach, we demonstrate safe inclusion of IL-1β as an adjuvant in vaccination strategies, leading to full protection of mice against a high influenza virus challenge dose by raising potent T cell responses. In conclusion, this paper proposes a class of IL-1β-based vaccine adjuvants and also provides further insight in the mechanics of cellular immune responses driven by IL-1β. [ABSTRACT FROM AUTHOR]

When animals are faced with a life-threatening challenge, they mount an organism-wide response (i.e. Plan A). For example, both the stress response (i.e. fight-or-flight) and the immune response recruit molecular resources from other body tissues, and induce physiological changes that optimize the body for defense. However, pathogens and predators often co-occur. Animals that can optimize responses for a dual challenge, i.e. simultaneous predator and pathogen attacks, will have a selective advantage. Responses to a combined predator and pathogen attack have not been well studied, but this paper summarizes the existing literature in insects. The response to dual challenges (i.e. Plan B) results in a suite of physiological changes that are different from either the stress response or the immune response, and is not a simple summation of the two. It is also not a straight-forward trade-off of one response against the other. The response to a dual challenge (i.e. Plan B) appears to resolve physiological trade-offs between the stress and immune responses, and reconfigures both responses to provide the best overall defense. However, the dual response appears to be more costly than either response occurring singly, resulting in greater damage from oxidative stress, reduced growth rate, and increased mortality. [ABSTRACT FROM AUTHOR]

Mycobacterium tuberculosis remains the leading cause of death attributed to a single infectious organism. Bacillus Calmette-Guerin (BCG), the standard vaccine against M. tuberculosis, is thought to prevent only 5% of all vaccine-preventable deaths due to tuberculosis, thus an alternative vaccine is required. One of the principal barriers to vaccine development against M. tuberculosis is the complexity of the immune response to infection, with uncertainty as to what constitutes an immunological correlate of protection. In this paper, we seek to give an overview of the immunology of M. tuberculosis infection, and by doing so, investigate possible targets of vaccine development. This encompasses the innate, adaptive, mucosal and humoral immune systems. Though MVA85A did not improve protection compared with BCG alone in a large-scale clinical trial, the correlates of protection this has revealed, in addition to promising results from candidate such as VPM1002, M72/ASO1E and H56:IC31 point to a brighter future in the field of TB vaccine development. [ABSTRACT FROM AUTHOR]

Immunotherapy, by enhancing the endogenous anti-tumor immune responses, is showing promising results for the treatment of numerous cancers refractory to conventional therapies. However, its effectiveness for advanced castration-resistant prostate cancer remains unsatisfactory and new therapeutic strategies need to be developed. To this end, systems pharmacology modeling provides a quantitative framework to test in silico the efficacy of new treatments and combination therapies. In this paper we present a new Quantitative Systems Pharmacology (QSP) model of prostate cancer immunotherapy, calibrated using data from pre-clinical experiments in prostate cancer mouse models. We developed the model by using Ordinary Differential Equations (ODEs) describing the tumor, key components of the immune system, and seven treatments. Numerous combination therapies were evaluated considering both the degree of tumor inhibition and the predicted synergistic effects, integrated into a decision tree. Our simulations predicted cancer vaccine combined with immune checkpoint blockade as the most effective dual-drug combination immunotherapy for subjects treated with androgen-deprivation therapy that developed resistance. Overall, the model presented here serves as a computational framework to support drug development, by generating hypotheses that can be tested experimentally in pre-clinical models. [ABSTRACT FROM AUTHOR]

This paper examines the effect of TET1 expression on survival in glioma patients using open-access data from the Genomic Data Commons. A neural network-based survival model was built on expression data from a selection of genes most affected by TET1 knockdown with a median cross-validated survival concordance of 82.5%. A synthetic experiment was then conducted that linked two separately trained neural networks: a multitask model estimating cancer hallmark gene expression from TET1 expression, and a survival neural network. This experiment quantified the mediation of the TET1 survival effect through eight cancer hallmarks: apoptosis, cell cycle, cell death, cell motility, DNA repair, immune response, two phosphorylation pathways, and a randomized gene sets. Immune response, DNA repair, and apoptosis displayed greater mediation than the randomized gene set. Cell motility was inversely associated with only 12.5% mediated concordance. We propose the neural network linkage mediation experiment as an approach to collecting evidence of hazard mediation relationships with prognostic capacity useful for designing interventions. [ABSTRACT FROM AUTHOR]