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Background: For thousands of years till nowadays, Nigella sativa (NS) has served as a common spice and food preservative. Its seed extracts, seed oil, and essential oil in traditional medicine have been used to remedy many ailments such as headaches, fever, gastric complaints, and even rheumatism. In addition, the antibacterial, virucidal, fungicidal, and antiparasitic properties of NS are well known. However, studies on the possible immunomodulatory effects of black cumin are relatively scarce. This article discusses in vitro and in vivo research supporting the immunomodulatory role of NS. Methods: The review is based on articles, books, and conference papers printed until September 2022, found in the Web of Science, PubMed, Wiley Online Library, and Google Scholar databases. Results: Experimental findings were reported concerning the ability of NS to modulate inflammation and immune responses or cytotoxic activity. Conclusions: All results suggest that NS can potentially be employed in developing effective therapeutic agents for regulating immune reactions. [ABSTRACT FROM AUTHOR]

The purpose of this paper is to present evidence that supports the notion that the primary reason behind marginal bone loss and implant failure is immune-based and that bacterial actions in the great majority of problematic cases are of a secondary nature. Materials and Methods: The paper is written as a narrative review. Results: Evidence is presented that commercially pure titanium is not biologically inert, but instead activates the innate immune system of the body. For its function, the clinical implant is dependent on an immune/inflammatory defense against bacteria. Biologic models such as ligature studies have incorrectly assumed that the primary response causing marginal bone loss is due to bacterial action. In reality, bacterial actions are secondary to an imbalance of the innate immune system caused by the combination of titanium implants and ligatures, ie, nonself. This immunologic imbalance may lead to marginal bone resorption even in the absence of bacteria. Conclusion: Marginal bone loss and imminent oral implant failure cannot be properly analyzed without a clear understanding of immunologically caused tissue responses. [ABSTRACT FROM AUTHOR]

TANK-binding kinase 1 (TBK1) is a member of the IKK family and plays a crucial role in the activation of non-canonical NF-kB signaling and type I interferon responses. The aberrant activation of TBK1 contributes to the proliferation and survival of various types of tumor cells, particularly in specific mutational or tumorous contexts. Inhibitors targeting TBK1 are under development and application in both in vivo and in vitro settings, yet their clinical efficacy remains limited. Numerous literatures have shown that TBK1 can exhibit both tumor promoting and tumor inhibiting effects. TBK1 acts as a pivotal node within the innate immune pathway, mediating anti-tumor immunity through the activation of innate immune responses. Facilitating interferon-I (IFN-I) production represents a critical mechanism through which TBK1 bridges these processes. IFN has been shown to exert both beneficial and detrimental effects on tumor progression. Hence, the paradoxical role of TBK1 in tumor development may necessitate acknowledgment in light of its downstream IFNI signaling cascade. In this paper, we review the signaling pathways mediated by TBK1 in various tumor contexts and summarize the dual roles of TBK1 and the TBK1-IFN pathways in both promoting and inhibiting tumor progression. Additionally, we highlight the significance of the TBK1-IFN pathway in clinical therapy, particularly in the context of immune response. We anticipate further advancements in the development of TBK1 inhibitors as part of novel cancer treatment strategies. [ABSTRACT FROM AUTHOR]

Deamidation is a post-translational chemical modification that occurs within proteins and can be influenced by many factors, including temperature and pH. In vaccines, deamidation is considered undesirable as it may lead to changes in structure, function, stability, and immunogenicity. Detecting deamidation in vaccines, especially adjuvanted vaccines, can be challenging due to the lack of simple quantitative techniques. In this study, the quantification of isoaspartic acid (isoAsp) was used to assess deamidation in model antigens in the presence and absence of common vaccine adjuvants. This study shows that the detection of isoAsp was possible in the presence of various types of adjuvants with little to no interference. High levels of isoAsp were detected in thermally and pH-stressed adjuvanted vaccines, suggesting significant deamidation and highlighting the stability-indicating capabilities of the assay. The quantification of isoAsp in stability programs of a vaccine drug product could possibly find applications in product shelf-life determination, using thermal kinetic modeling to predict deamidation over time. The ability to detect deamidation early in vaccine development enhances process improvements and ultimately improves the vaccine's stability. To summarize, this paper describes a rapid and simple method to determine deamidation in adjuvanted vaccines. This method could be applicable to formulation development, stability assessment, or shelf-life determination. [ABSTRACT FROM AUTHOR]

Hepatitis E (Hepatitis E, HE) is an acute and chronic infectious hepatitis caused by hepatitis E virus (Hepatitis E Virus, HEV) infection, which is responsible for most acute hepatitis in the world and is a significant public health problem. The pathogen, HEV, has three Open Reading Frames (ORFs) ORF1, ORF2, and ORF3, each of which has a different function. Most of the current research is focused on ORF1 and ORF2, while the research on ORF3 is still relatively small. To provide more ideas for the study of HEV pathogenesis and the prevention and treatment of HE, this paper reviews the effects of ORF3 on the ERK pathway, growth factors, immune response, and virus release. [ABSTRACT FROM AUTHOR]

Sepsis is a clinical syndrome caused by uncontrollable immune dysregulation triggered by pathogen infection, characterized by high incidence, mortality rates, and disease burden. Current treatments primarily focus on symptomatic relief, lacking specific therapeutic interventions. The core mechanism of sepsis is believed to be an imbalance in the host's immune response, characterized by early excessive inflammation followed by late immune suppression, triggered by pathogen invasion. This suggests that we can develop immunotherapeutic treatment strategies by targeting and modulating the components and immunological functions of the host's innate and adaptive immune systems. Therefore, this paper reviews the mechanisms of immune dysregulation in sepsis and, based on this foundation, discusses the current state of immunotherapy applications in sepsis animal models and clinical trials. [ABSTRACT FROM AUTHOR]

The application of mathematical biology and dynamical systems has proven to be an effective approach for studying viral infection models. To contribute to this research, our paper proposes a new CHIKV model that takes into account an adaptive immune response and distributed time delays, which accurately reflects the time lag between initial viral contacts and the production of new active CHIKV particles. By analyzing the model’s qualitative behavior, we establish a biological threshold number that can predict whether CHIKV will be cleared from or persist in the body. We demonstrate the global stability of both CHIKV-present and CHIKV-free steady states using the Lyapunov functional method and LaSalle’s invariance principle. In addition, we conduct numerical simulations to examine how time delays can affect the stability of the steady states. Through these simulations, we gain insights into how varying time delays can influence the persistence or clearance of CHIKV within the host. [ABSTRACT FROM AUTHOR]

In this paper, a dynamic HIV model with cell-to-cell transmission, two immune responses, and induced apoptosis is proposed and studied. First, the non-negativity and boundedness of the solutions of the model are given, and then the exact expression of the basic reproduction number R0 is obtained by using the next generation matrix method. Second, criteria are obtained for the local stability of the disease-free equilibrium, immune response-free equilibrium, and the infected equilibrium with both humoral and cellular immune responses. Furthermore, the threshold conditions are also derived for the global asymptotic stability of the disease-free equilibrium, immune responsefree equilibrium, and the infected equilibrium with both humoral and cellular immune responses by constructing the suitable Lyapunov function. Finally, some numerical simulations are conducted to verify the theoretical results; the numerical simulation results show that the increase of apoptosis rate had a positive role in the control of viral infection. [ABSTRACT FROM AUTHOR]

Cancer diseases constitute a major health problem which leads to the death of millions of people annually. They are unique among other diseases because cancer cells can perfectly adapt to the environment that they create themselves. This environment is usually highly hostile and for normal cells it would be hugely difficult to survive, however neoplastic cells not only can survive but also manage to proliferate. One of the reasons is that they can alter immunological pathways which allow them to be flexible and change their phenotype to the one needed in specific conditions. The aim of this paper is to describe some of these immunological pathways that play significant roles in gynecologic neoplasms as well as review recent research in this field. It is of high importance to possess extensive knowledge about these processes, as greater understanding leads to creating more specialized therapies which may prove highly effective in the future. [ABSTRACT FROM AUTHOR]

Tumor–immune system interactions are very complicated, being highly nonlinear and not well understood. A large number of tumors can potentially weaken the immune system through various mechanisms such as secreting cytokines that suppress the immune response. In this paper, we propose a tumor–immune system interaction model with a nonmonotonic immune response function and adoptive cellular immunotherapy (ACI). The model has a tumor-free equilibrium and at most three tumor-presence equilibria (low, moderate and high ones). The stability of all equilibria is studied by analyzing their characteristic equations. The consideration of nonmonotonic immune response results in a series of bifurcations such as the saddle-node bifurcation, transcritical bifurcation, Hopf bifurcation and Bogdanov–Takens bifurcation. In addition, numerical simulation results show the coexistence of periodic orbits and homoclinic orbits. Interestingly, along with various bifurcations, we also found two bistable scenarios: the coexistence of a stable tumor-free as well as a high-tumor-presence equilibrium and the coexistence of a stable-low as well as a high-tumor-presence equilibrium, which can show symmetric and antisymmetric properties in a range of model parameters and initial cell concentrations. The new findings indicate that under ACI, patients can possibly reach either a stable tumor-free state or a low-tumor-presence state in the presence of nonmonotonic immune response once the immune system is activated. [ABSTRACT FROM AUTHOR]

The immune system interacts with many nominal 'danger' signals, endogenous danger‐associated (DAMP), exogenous pathogen (PAMP) and allergen (AAMP)‐associated molecular patterns. The immune context under which these are received can promote or prevent immune activating or inflammatory mechanisms and may orchestrate diverse immune responses in allergy and cancer. Each can act either by favouring a respective pathology or by supporting the immune response to confer protective effects, depending on acuity or chronicity. In this Position Paper under the collective term danger signals or DAMPs, PAMPs and AAMPs, we consider their diverse roles in allergy and cancer and the connection between these in AllergoOncology. We focus on their interactions with different immune cells of the innate and adaptive immune system and how these promote immune responses with juxtaposing clinical outcomes in allergy and cancer. While danger signals present potential targets to overcome inflammatory responses in allergy, these may be reconsidered in relation to a history of allergy, chronic inflammation and autoimmunity linked to the risk of developing cancer, and with regard to clinical responses to anti‐cancer immune and targeted therapies. Cross‐disciplinary insights in AllergoOncology derived from dissecting clinical phenotypes of common danger signal pathways may improve allergy and cancer clinical outcomes. [ABSTRACT FROM AUTHOR]

Introduction Curcumin, the active ingredient in turmeric, is gaining increasing attention due to its potential health benefits, especially in the context of its immunomodulatory and anticancer properties. Aim of the study The aim of this review was to discuss recent findings regarding the impact of curcumin on the immune system and its potential applications in anticancer therapy. Materials and methods The paper was created based on the Pubmed and Scholar database. The literature was reviewed using the keywords: „curcumin", „immunomodulatory effects", „cytokines", „anticancer", „apoptosis", „cell proliferation", „radiosensitizing". Results Studies have confirmed that curcumin, especially in the form of nanocurcumin, exhibits significant immunomodulatory effects. It reduces the number of Th17 cells, increases Treg cells, and regulates the expression of pro-inflammatory cytokines, which is crucial in controlling autoimmune reactions. Furthermore, it demonstrates anticancer activity by inhibiting the growth of cancer cells, stimulating apoptosis, and enhancing the effectiveness of anticancer therapy. Conclusions Despite promising results, further research on the safety of curcumin therapy, particularly in the long term, is essential. Limitations associated with bioavailability and pharmacokinetics suggest the need for the development of formulations with increased bioavailability to maximize the potential benefits of curcumin in the treatment of various disorders. [ABSTRACT FROM AUTHOR]

Cancer immunotherapy has recently emerged as a key strategy for cancer treatment. TREM2, a key target for regulating the tumor immune microenvironment, is important in cancer treatment and progression. TREM2 is an immune signaling hub that regulates multiple pathological pathways. It not only suppresses anti-tumor immune responses by inhibiting T cell-mediated immune responses, but it also influences tumorigenesis by affecting NK cell-mediated antitumor immunity. Noticeably, TREM2 expression levels also vary significantly among different tumor cells, and it can regulate tumor progression by modulating various signaling pathways. Above all, by summarizing the role of TREM2 in cancer immunotherapy and the mechanism by which TREM2 regulates tumor progression, this paper clarifies TREM2's role in both tumor progression and cancer therapy, identifying a new therapeutic target for oncology diseases. [ABSTRACT FROM AUTHOR]

Periodontal disease is an inflammatory condition that affects the periodontium and results in the destruction of periodontal tissue. Cytokines are small, non-structural proteins with inferior molecular weights which have an intricate organizational effect on inflammation and immunity. Immune reaction against products of bacteria and the resulting generation of inflammatory cytokines are significant contributors to periodontal tissue injury. In this disease inflammatory cytokines are generated by immune cells to attack the periodontal bacteria. A persistent or strong immune response may cause inflammation and the creation of cytokines that are essential in the development of periodontitis, even though the immune response can defend an organism from a variety of diseases. Clarifying the immunomodulatory role of cytokines in periodontitis was the main goal of this review. Using suitable keywords, relevant papers would be searched in the scientific databases Scopus, Google Scholar, PubMed, and Web of Science. In conclusion cytokines control and modulate the immune response in periodontitis. Covered studies were posted between 2000 and 2023 and detect great variance in patients' selection, clinical assessments, and cytokines measures. A significant association between cytokines and periodontitis developments was reported in some studies. Cytokines are control and modulate the immune response in periodontitis. [ABSTRACT FROM AUTHOR]

Systemic sclerosis (SSc) is a rare autoimmune connective tissue disorder characterized by massive fibrosis, vascular damage, and immune imbalance. Advances in rheumatology and immunology over the past two decades have led to a redefinition of systemic sclerosis, shifting from its initial perception as primarily a "hyperfibrotic" state towards a recognition of systemic sclerosis as an immune-mediated disease. Consequently, the search for genetic markers has transitioned from focusing on fibrotic mechanisms to exploring immune regulatory pathways. Immunogenetics, an emerging field at the intersection of immunology, molecular biology, and genetics has provided valuable insights into inherited factors that influence immunity. Data from genetic studies conducted thus far indicate that alterations in genetic messages can significantly impact disease risk and progression. While certain genetic variations may confer protective effects, others may exacerbate disease susceptibility. This paper presents a comprehensive review of the most relevant genetic changes that influence both the risk and course of systemic sclerosis. Special emphasis is placed on factors regulating the immune response, recognizing their pivotal role in the pathogenesis of the disease. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs) are specialized antigen-presenting cells that are crucial for maintaining self-tolerance, initiating immune responses against pathogens, and patrolling body compartments. Despite promising aspects, DC-based immunotherapy faces challenges that include limited availability, immune escape in tumors, immunosuppression in the tumor microenvironment, and the need for effective combination therapies. A further limitation in DC-based immunotherapy is the low population of migratory DC (around 5%–10%) that migrate to lymph nodes (LNs) through afferent lymphatics depending on the LN draining site. By increasing the population of migratory DCs, DC-based immunotherapy could enhance immunotherapeutic effects on target diseases. This paper reviews the importance of DC migration and current research progress in the context of DC-based immunotherapy. [ABSTRACT FROM AUTHOR]

One of the most effective strategies to fight viruses and handle health diseases is vaccination. Recent studies and current applications are moving on antigen, DNA and RNA-based vaccines to overcome the limitations related to the conventional vaccination strategies, such as low safety, necessity of multiple injection, and side effects. However, due to the instability of pristine antigen, RNA and DNA molecules, the use of nanocarriers is required. Among the different nanocarriers proposed for vaccinal applications, three types of nanovesicles were selected and analysed in this review: liposomes, transfersomes and niosomes. PubMed, Scopus and Google Scholar databases were used for searching recent papers on the most frequently used conventional and innovative methods of production of these nanovesicles. Weaknesses and limitations of conventional methods (i.e., multiple post-processing, solvent residue, batch-mode processes) can be overcome using innovative methods, in particular, the ones assisted by supercritical carbon dioxide. SuperSomes process emerged as a promising production technique of solvent-free nanovesicles, since it can be easily scaled-up, works in continuous-mode, and does not require further post-processing steps to obtain the desired products. As a result of the literature analysis, supercritical carbon dioxide assisted methods attracted a lot of interest for nanovesicles production in the vaccinal field. However, despite their numerous advantages, supercritical processes require further studies for the production of liposomes, transfersomes and niosomes with the aim of reaching well-defined technologies suitable for industrial applications and mass production of vaccines. [ABSTRACT FROM AUTHOR]

In this paper, a fractional order HIV/HTLV co-infection model with HIV-specific antibody immune response is established. Two cases are considered: constant control and optimal control. For the constant control system, the existence and uniqueness of the positive solutions are proved, and then the sufficient conditions for the existence and stability of five equilibriums are obtained. For the second case, the Pontryagin's Maximum Principle is used to analyze the optimal control, and the formula of the optimal solution are derived. After that, some numerical simulations are performed to validate the theoretical prediction. Numerical simulations indicate that in the case of HIV/HTLV co-infection, the concentration of CD4+T cells is no longer suitable as an effective reference data for understanding the development process of the disease. On the contrary, the number of HIV virus particles should be used as an important indicator for reference. [ABSTRACT FROM AUTHOR]

Disruption of the airway epithelium triggers a defensive immune response that begins with the production and release of alarmin cytokines. These epithelial-derived alarmin cytokines, including thymic stromal lymphopoietin (TSLP), are produced in response to aeroallergens, viruses, and toxic inhalants. An alarmin response disproportionate to the inhaled trigger can exacerbate airway diseases such as asthma. Allergens inhaled into previously sensitized airways are known to drive a T2 inflammatory response through the polarization of T cells by dendritic cells mediated by TSLP. Harmful compounds found within air pollution, microbes, and viruses are also triggers causing airway epithelial cell release of TSLP in asthmatic airways. The release of TSLP leads to the development of inflammation which, when unchecked, can result in asthma exacerbations. Genetic and inheritable factors can contribute to the variable expression of TSLP and the risk and severity of asthma. This paper will review the various triggers and consequences of TSLP release in asthmatic airways. [ABSTRACT FROM AUTHOR]

Simple Summary: The increasing demand for livestock production with a more sustainable approach to reduce greenhouse emissions offers the opportunity to test essential oils (EOs), as natural treatments, for their effect on rumen activity, as well as the use of antibiotics, for their antimicrobial activities. However, little information is available on the effects of EOs on the proliferative immune response and cytokine production. Therefore, the present paper is aimed at evaluating the effect of the Mentha x piperita L., Rosmarinus officinalis L., and Lavandula angustifolia L. EOs on sheep peripheral blood monocular cells' bio-response in terms of viability, proliferation, and cytokine secretion. The main results obtained encourage the implementation of these EOs as feed additives, in in vivo studies, to improve the animals' immune competence, especially those under specific physiological or environmental stressors. Recently, the uses of essential oils (EOs) as rumen modifiers, anti-inflammatory agents, and antioxidants were demonstrated in livestock. In the present study, the role of Mentha x piperita L. (MEO), Rosmarinus officinalis L. (REO), and Lavandula angustifolia L. (LEO) EOs in an in vitro sheep model of inflammation was investigated. With this aim, peripheral blood mononuclear cells (PBMCs) were treated with incremental concentrations (3, 5, 7, and 10%) of each EO to test their effects on cell viability and proliferation and on interleukin (IL)-6, IL-10, and IL-8 secretion. The PBMCs were stimulated by Concanavalin A (ConA) alone or in combination with lipopolysaccharide (LPS) mitogen. The positive and negative controls were represented by PBMCs in the presence or absence, respectively, of mitogens only. The cell viability and proliferation were determined by XTT and BrdU assays, while the cytokines were analyzed by ELISA. The EO treatments did not affect the viability; on the contrary, the PBMC proliferation increased in presence of all the EOs tested, according to the different percentages and mitogens used. The IL-10 secretion was higher in both the REO and the LEO tested at 3% than in the positive control; furthermore, the IL-8 level was influenced differently by the various EOs. The present data demonstrate that EOs may modulate the immune response activated by inflammation. [ABSTRACT FROM AUTHOR]

DNA oncoviruses represent an intriguing subject due to their involvement in oncogenesis. These viruses have evolved mechanisms to manipulate the host immune response, facilitating their persistence and actively contributing to carcinogenic processes. This paper describes the complex interactions between DNA oncoviruses and the innate immune system, with a particular emphasis on the cGAS-STING pathway. Exploring these interactions highlights that DNA oncoviruses strategically target and subvert this pathway, exploiting its vulnerabilities for their own survival and proliferation within the host. Understanding these interactions lays the foundation for identifying potential therapeutic interventions. Herein, we sought to contribute to the ongoing efforts in advancing our understanding of the innate immune system in oncoviral pathogenesis. [ABSTRACT FROM AUTHOR]

Recurrent miscarriage, poses a significant challenge for many couples globally, the causes of which are not fully understood. Recent studies have shown the intricate link between uterine inflammation and recurrent miscarriages. While inflammation is essential during early pregnancy stages, especially in embryo implantation, an imbalance can lead to miscarriage. Key inflammatory mediators and an imbalance in immune cells can significantly alter and contribute to recurrent miscarriages. Lifestyle factors like smoking and obesity exacerbate inflammatory responses, increasing miscarriage risks. Understanding the interaction between the uterine environment, immune cell imbalances, and recurrent miscarriages is essential for devising effective treatments. This paper presents the latest data on inflammation's role in recurrent miscarriage, emphasizing the significance of diagnosing chronic endometritis and immune imbalances, offering practical recommendations for treatment and diagnosis. [ABSTRACT FROM AUTHOR]

Nowadays the problem of food allergy is of great importance. It impairs the quality of life of people all over the world. People suffer from food allergies starting from the earliest period of life. Usually, people get antihistamine remedies with a variety of side effects. Food allergy may be caused by various allergens and its development depends on different factors. The aetio-pathogenic treatment used to be elaborated. Gut microbiota plays a crucial role in maintaining of homeostasis of any organism with a gastrointestinal tract. Human beings are not exceptions. The human gastrointestinal tract is enormously colonized by various microorganisms, which localize predominantly in the colon in a symbiotic relationship with the host. Impairment of microbiota function causes different diseases of the host including food allergy. The work aims to analyse the literature of the last decade (2013-2023) to reveal the connection between the condition of microbiota and its role in the development of food allergy. Scientific articles from MEDLINE-PubMed, Embase, and Cochrane databases were analysed in the work. A set of "MeSH terms" was created to remove a large number of irrelevant papers during the manual search. It was settled that the content of microbiota and its functional activity is of great importance for food allergy development both in infants and adults. The main problem lies in the synthesis of the short-chain fatty acids and their interrelation. The characteristics of the colon epithelial barrier, its adhesive qualities, and permeability, which depend on the functional activity of microbiota, also influence on development of food allergy. Intestinal microbiota is essential for maintaining of intestinal epithelial barrier, which plays one of the pivotal roles in intestinal health and provides homeostasis keeping. Microbiota destruction by antibiotics or other exogenic/endogenic factors leads to impairment of the intestinal epithelial barrier, which in turn serves as a trigger of inflammation and allows pathogens and allergens passage from the intestinal cavity into the bloodstream. [ABSTRACT FROM AUTHOR]

Simple Summary: Uterine health is crucial for cows to become pregnant and maintain farm profitability. However, when cows suffer from uterine diseases, it not only affects their fertility but also leads to increased antibiotic usage, impacting both animal health and farm economics. Probiotics, which are beneficial bacteria, offer a promising solution to improve cow health and reproductive success. Research suggests that certain probiotics can enhance cow fertility. Administering these probiotics directly into the cow's vagina may strengthen uterine health, especially after giving birth. While initial findings are promising, further large-scale studies are needed to confirm their effectiveness. This paper underscores the importance of establishing clear guidelines for using probiotics in cow management, including selecting appropriate strains and administering them correctly. Moving forward, continued research is necessary to fully understand the benefits of probiotics in maintaining cow health and improving fertility. Uterine disease in cattle impairs reproductive performance and profitability and increases antibiotic use and antimicrobial resistance. Thus, probiotics offer a promising alternative therapy. This review presents conceptual findings on the efficacy of probiotics in managing uterine diseases and fertility in cows. Probiotics containing Lactobacillus spp. and Bifidobacterium spp. individually or as composite formulations are known to improve fertility. Strategic intravaginal administration of these formulations would likely enhance uterine immunity, particularly during the postpartum period. While current findings on the benefits to uterine health are encouraging, there is still significant knowledge missing, including a lack of empirical information from large-scale field trials. This review underscores the need for evidence-based guidelines for probiotics, such as genomic selection of formulations, targeted delivery, or potential synergy with other interventions. Future research should address these gaps to maximize the potential of probiotics in managing uterine diseases and enhancing the reproductive health of dairy cattle. [ABSTRACT FROM AUTHOR]

Since its emergence in late 2019, SARS-CoV-2 has diversified into a large number of lineages and caused multiple waves of infection globally. Novel lineages have the potential to spread rapidly and internationally if they have higher intrinsic transmissibility and/or can evade host immune responses, as has been seen with the Alpha, Delta, and Omicron variants of concern. They can also cause increased mortality and morbidity if they have increased virulence, as was seen for Alpha and Delta. Phylogenetic methods provide the "gold standard" for representing the global diversity of SARS-CoV-2 and to identify newly emerging lineages. However, these methods are computationally expensive, struggle when datasets get too large, and require manual curation to designate new lineages. These challenges provide a motivation to develop complementary methods that can incorporate all of the genetic data available without down-sampling to extract meaningful information rapidly and with minimal curation. In this paper, we demonstrate the utility of using algorithmic approaches based on word-statistics to represent whole sequences, bringing speed, scalability, and interpretability to the construction of genetic topologies. While not serving as a substitute for current phylogenetic analyses, the proposed methods can be used as a complementary, and fully automatable, approach to identify and confirm new emerging variants. [ABSTRACT FROM AUTHOR]

As one of the traditional Chinese herbs, Danshen (Salvia miltiorrhiza Bunge) has been widely studied and widely used in the treatment of cardiovascular, cerebrovascular, and other immune diseases. Tanshinones and salvianolic acids isolated from Danshen are considered to be the main components of its biological activity and pharmacology that play important roles in increasing the index of immune organs, regulating the number and function of immune cells, and releasing immunoreactive substances. Especially tanshinone IIA, cryptotanshinone, salvianolic acid B, and rosmarinic acid show good biological activity in treating rheumatoid arthritis, some immune-mediated inflammatory diseases, psoriasis, and inflammatory bowel disease. In order to understand their pharmacological effects and provide references for future research and clinical treatment, the regulation of immune response by tanshinones and salvianolic acids is summarized in detail in this paper. In addition, the challenges in their pharmacological development and the opportunities to exploit their clinical potential have been documented. [ABSTRACT FROM AUTHOR]

Promoting the efficiency of bone regeneration in bone loss diseases is a significant clinical challenge. Traditional therapies often fail to achieve better therapeutic outcomes and shorter treatment times. However, in recent years, extracellular vesicles (EVs) have gained significant attention due to their exceptional osteogenic function in bone regeneration and superior therapeutic effects compared to traditional cell therapy. EVs have emerged as a promising therapy for tissue defect regeneration due to their various physiological functions, such as regulating the immune response and promoting tissue repair and regeneration. Moreover, EVs have good biocompatibility, low immunogenicity, and long-term stability, and can be improved through pretreatment and other methods. Studies investigating the mechanisms by which extracellular vesicles promote bone regeneration and applying EVs from different sources using various methods to animal models of bone defects have increased. Therefore, this paper reviews the types of EVs used for bone regeneration, their sources, roles, delivery pathways, scaffold biomaterials, and applications. [ABSTRACT FROM AUTHOR]

Natural killer (NK) cells are unique from other immune cells in that they can rapidly kill multiple neighboring cells without the need for antigenic pre-sensitization once the cells display surface markers associated with oncogenic transformation. Given the dynamic role of NK cells in tumor surveillance, NK cell-based immunotherapy is rapidly becoming a "new force" in tumor immunotherapy. However, challenges remain in the use of NK cell immunotherapy in the treatment of solid tumors. Many metabolic features of the tumor microenvironment (TME) of solid tumors, including oxygen and nutrient (e.g., glucose, amino acids) deprivation, accumulation of specific metabolites (e.g., lactate, adenosine), and limited availability of signaling molecules that allow for metabolic reorganization, multifactorial shaping of the immune-suppressing TME impairs tumor-infiltrating NK cell function. This becomes a key barrier limiting the success of NK cell immunotherapy in solid tumors. Restoration of endogenous NK cells in the TME or overt transfer of functionally improved NK cells holds great promise in cancer therapy. In this paper, we summarize the metabolic biology of NK cells, discuss the effects of TME on NK cell metabolism and effector functions, and review emerging strategies for targeting metabolism-improved NK cell immunotherapy in the TME to circumvent these barriers to achieve superior efficacy of NK cell immunotherapy. [ABSTRACT FROM AUTHOR]

Taking into account the effects of the immune response and delay, and complexity on HIV-1 transmission, a multiscale AIDS/HIV-1 model is formulated in this paper. The multiscale model is described by a within-host fast time model with intracellular delay and immune delay, and a between-host slow time model with latency delay. The dynamics of the fast time model is analyzed, and includes the stability of equilibria and properties of Hopf bifurcation. Further, for the coupled slow time model without an immune response, the basic reproduction number R 0 h is defined, which determines whether the model may have zero, one, or two positive equilibria under different conditions. This implies that the slow time model demonstrates more complex dynamic behaviors, including saddle-node bifurcation, backward bifurcation, and Hopf bifurcation. For the other case, that is, the coupled slow time model with an immune response, the threshold dynamics, based on the basic reproduction number R ˜ 0 h , is rigorously investigated. More specifically, if R ˜ 0 h < 1 , the disease-free equilibrium is globally asymptotically stable; if R ˜ 0 h > 1 , the model exhibits a unique endemic equilibrium that is globally asymptotically stable. With regard to the coupled slow time model with an immune response and stable periodic solution, the basic reproduction number R 0 is derived, which serves as a threshold value determining whether the disease will die out or lead to periodic oscillations in its prevalence. The research results suggest that the disease is more easily controlled when hosts have an extensive immune response and the time required for new immune particles to emerge in response to antigenic stimulation is within a certain range. Finally, numerical simulations are presented to validate the main results and provide some recommendations for controlling the spread of HIV-1. [ABSTRACT FROM AUTHOR]

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]

This paper explores the dynamics analysis of a human immunodeficiency virus (HIV) model with saturated cytotoxic T lymphocyte (CTL) immune response and Beddington–DeAngelis infection rate. There are two time delays in the model to describe the time needed for infection of cell and CTL immune response generation, respectively. We obtain two thresholds and three possible equilibria from the model. By analyzing the corresponding characteristic equations, we study the stabilities of equilibrium and the effect of delays on CTL immune response. The results indicate that when immune delay is present, the steady state of equilibrium is disrupted and leads to a Hopf bifurcation. Finally, we use sensitivity analyses to show the effect of parameters on thresholds and numerical simulations to illustrate the theoretical results. [ABSTRACT FROM AUTHOR]

Gasdermin D (GSDMD)-mediated pyroptotic cell death drives inflammatory cytokine release and downstream immune responses upon inflammasome activation, which play important roles in host defense and inflammatory disorders. Upon activation by proteases, the GSDMD N-terminal domain (NTD) undergoes oligomerization and membrane translocation in the presence of lipids to assemble pores. Despite intensive studies, the molecular events underlying the transition of GSDMD from an autoinhibited soluble form to an oligomeric pore form inserted into the membrane remain incompletely understood. Previous work characterized S-palmitoylation for gasdermins from bacteria, fungi, invertebrates, as well as mammalian gasdermin E (GSDME). Here, we report that a conserved residue Cys191 in human GSDMD was S-palmitoylated, which promoted GSDMD-mediated pyroptosis and cytokine release. Mutation of Cys191 or treatment with palmitoyltransferase inhibitors cyano-myracrylamide (CMA) or 2-bromopalmitate (2BP) suppressed GSDMD palmitoylation, its localization to the membrane and dampened pyroptosis or IL-1β secretion. Furthermore, Gsdmd-dependent inflammatory responses were alleviated by inhibition of palmitoylation in vivo. By contrast, coexpression of GSDMD with palmitoyltransferases enhanced pyroptotic cell death, while introduction of exogenous palmitoylation sequences fully restored pyroptotic activities to the C191A mutant, suggesting that palmitoylation-mediated membrane localization may be distinct from other molecular events such as GSDMD conformational change during pore assembly. Collectively, our study suggests that S-palmitoylation may be a shared regulatory mechanism for GSDMD and other gasdermins, which points to potential avenues for therapeutically targeting S-palmitoylation of gasdermins in inflammatory disorders. [ABSTRACT FROM AUTHOR]

Background: In many countries, infant vaccination with acellular pertussis (aP) vaccines has replaced use of more reactogenic whole-cell pertussis (wP) vaccines. Based on immunological and epidemiological evidence, we hypothesised that substituting the first aP dose in the routine vaccination schedule with wP vaccine might protect against IgE-mediated food allergy. We aimed to compare reactogenicity, immunogenicity, and IgE-mediated responses of a mixed wP/aP primary schedule versus the standard aP-only schedule. Methods and findings: OPTIMUM is a Bayesian, 2-stage, double-blind, randomised trial. In stage one, infants were assigned (1:1) to either a first dose of a pentavalent wP combination vaccine (DTwP-Hib-HepB, Pentabio PT Bio Farma, Indonesia) or a hexavalent aP vaccine (DTaP-Hib-HepB-IPV, Infanrix hexa, GlaxoSmithKline, Australia) at approximately 6 weeks old. Subsequently, all infants received the hexavalent aP vaccine at 4 and 6 months old as well as an aP vaccine at 18 months old (DTaP-IPV, Infanrix-IPV, GlaxoSmithKline, Australia). Stage two is ongoing and follows the above randomisation strategy and vaccination schedule. Ahead of ascertainment of the primary clinical outcome of allergist-confirmed IgE-mediated food allergy by 12 months old, here we present the results of secondary immunogenicity, reactogenicity, tetanus toxoid IgE-mediated immune responses, and parental acceptability endpoints. Serum IgG responses to diphtheria, tetanus, and pertussis antigens were measured using a multiplex fluorescent bead-based immunoassay; total and specific IgE were measured in plasma by means of the ImmunoCAP assay (Thermo Fisher Scientific). The immunogenicity of the mixed schedule was defined as being noninferior to that of the aP-only schedule using a noninferiority margin of 2/3 on the ratio of the geometric mean concentrations (GMR) of pertussis toxin (PT)-IgG 1 month after the 6-month aP. Solicited adverse reactions were summarised by study arm and included all children who received the first dose of either wP or aP. Parental acceptance was assessed using a 5-point Likert scale. The primary analyses were based on intention-to-treat (ITT); secondary per-protocol (PP) analyses were also performed. The trial is registered with ANZCTR (ACTRN12617000065392p). Between March 7, 2018 and January 13, 2020, 150 infants were randomised (75 per arm). PT-IgG responses of the mixed schedule were noninferior to the aP-only schedule at approximately 1 month after the 6-month aP dose [GMR = 0·98, 95% credible interval (0·77 to 1·26); probability (GMR > 2/3) > 0·99; ITT analysis]. At 7 months old, the posterior median probability of quantitation for tetanus toxoid IgE was 0·22 (95% credible interval 0·12 to 0·34) in both the mixed schedule group and in the aP-only group. Despite exclusions, the results were consistent in the PP analysis. At 6 weeks old, irritability was the most common systemic solicited reaction reported in wP (65 [88%] of 74) versus aP (59 [82%] of 72) vaccinees. At the same age, severe systemic reactions were reported among 14 (19%) of 74 infants after wP and 8 (11%) of 72 infants after aP. There were 7 SAEs among 5 participants within the first 6 months of follow-up; on blinded assessment, none were deemed to be related to the study vaccines. Parental acceptance of mixed and aP-only schedules was high (71 [97%] of 73 versus 69 [96%] of 72 would agree to have the same schedule again). Conclusions Compared to the aP-only schedule, the mixed schedule evoked noninferior PT-IgG responses, was associated with more severe reactions, but was well accepted by parents. Tetanus toxoid IgE responses did not differ across the study groups. Trial registration: Trial registered at the Australian and New Zealand Clinical 207 Trial Registry (ACTRN12617000065392p). https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=371998&isReview=true. Just one registry (as above). Gladymar Pérez Chacón and colleagues report the safety and immunogenicity of a mixed whole-cell and acellular pertussis vaccine in Australian infants in stage 1 of the two-stage OPTIMUM trial. Author summary: Why was this study done?: Evidence-based strategies to lower the risk of food allergies developing in young children are limited. A previous observational study suggested that food allergies appear to be less common among Australian-born children vaccinated with a first dose of whole-cell whooping cough (wP) vaccine before 4 months old versus those receiving a first dose of acellular whooping cough (aP) vaccine at the same age. Why did the researchers do and find?: In the first stage of a 2-stage, double-blind, noninferiority trial, Australian-born infants were randomised to receive a first dose of wP versus aP at approximately 6 weeks old; in both study groups, aP vaccine is given at 4 and 6 months old. Stage (phase) one examined the immunogenicity, reactogenicity, and IgE-mediated immune responses of the mixed vaccine schedule (wP/aP/aP) versus the standard aP-only vaccination strategy (aP/aP/aP) in a cohort of 150 infants; stage two is ongoing and was designed to ascertain the development of food allergy by 12 months old (primary outcome) in a cohort of up to 3,000 infants. At 7 months old, the mixed schedule was noninferior to the standard aP-only strategy with respect to pertussis toxin IgG responses; at the same age, we observed no difference across the study groups in IgE responses to hen's egg and tetanus toxoid antigens. The mixed schedule was more reactogenic but well accepted by parents. What do these findings mean?: These findings support the acceptable immunogenicity and reactogenicity of the mixed schedule and are relevant for countries in which wP and aP vaccines are licensed and readily available. While the reported IgE responses are not conclusive, further studies of CD4+ T cell polarisation in response to pertussis antigens, along with primary outcome data will provide a comprehensive picture of the atopic immunophenotypic responses across the study groups. Additional evidence is required to understand the population-level acceptability of the mixed vaccination strategy. [ABSTRACT FROM AUTHOR]

In vitro display technologies such as yeast display have been instrumental in developing the selection of new antibodies, antibody fragments or nanobodies that bind to a specific target, with affinity towards the target being the main factor that influences selection outcome. However, the roles of mechanical forces are being increasingly recognized as a crucial factor in the regulation and activation of effector cell function. It would thus be of interest to isolate binders behaving optimally under the influence of mechanical forces. We developed a microfluidic assay allowing the selection of yeast displaying nanobodies through antigen-specific immobilization on a surface under controlled hydrodynamic flow. This approach enabled enrichment of model yeast mixtures using tunable antigen density and applied force. This new force-based selection method opens the possibility of selecting binders by relying on both their affinity and force resistance, with implications for the design of more efficient immunotherapeutics. [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]

Leishmaniasis is a widespread disease transmitted by vectors and characterized by complex interactions between the host's immune system and the parasite. Leishmania, a protozoan parasite is the causative agent of the disease. This parasite has the ability to infect and thrive inside macrophages, which are the body's primary fighting cells. This review paper explores the various strategies employed by Leishmania to overcome the defensive mechanisms of macrophages and survive within the hostile intracellular environment. The study delves into the molecular mechanisms used by Leishmania to influence the process of phagolysosome maturation, evade immunological detection and exploit signaling pathways within macrophages. Furthermore, the paper underscores the significant role of host genetics and immune response variability in influencing the outcome of this host-pathogen interaction. A thorough understanding of the intricate interactions between Leishmania parasites and macrophages is essential in developing innovative therapeutic approaches to treat Leishmania infection. [ABSTRACT FROM AUTHOR]

In 2019, the SARS-CoV-2 virus caused one of the biggest virus pandemics called Coronavirus disease-19 (COVID-19). This virus has been responsible for the death of millions of people around the world. The biological function of SARS-CoV-2 and its pathophysiology mechanisms, as well as the host immunity against this virus, has attracted the attention of the scientific community all over the world. The current study reviewed innate and acquired immune responses following COVID-19 infection. These immune responses are probably involved in the severity of the disease and death. Also, the cause and consequence of potential clinical strategies to treat or prevent SARS-CoV-2 infection have been proposed. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is characterized by a rapid decline in renal function and is associated with a high morbidity and mortality rate. At present, the underlying mechanisms of AKI remain incompletely understood. Immune disorder is a prominent feature of AKI, and dendritic cells (DCs) play a pivotal role in orchestrating both innate and adaptive immune responses, including the induction of protective proinflammatory and tolerogenic immune reactions. Emerging evidence suggests that DCs play a critical role in the initiation and development of AKI. This paper aimed to conduct a comprehensive review and analysis of the role of DCs in the progression of AKI and elucidate the underlying molecular mechanism. The ultimate objective was to offer valuable insights and guidance for the treatment of AKI. [ABSTRACT FROM AUTHOR]

As a newly emerging organ transplantation technique, islet transplantation has shown the advantages of minimal trauma and high safety since it was first carried out. The proposal of the Edmonton protocol, which has been widely applied, was a breakthrough in this method. However, direct contact between islets and portal vein blood will cause a robust innate immune response leading to massive apoptosis of the graft, and macrophages play an essential role in the innate immune response. Therefore, therapeutic strategies targeting macrophages in the innate immune response have become a popular research topic in recent years. This paper will summarize and analyze recent research on strategies for regulating innate immunity, primarily focusing on macrophages, in the field of islet transplantation, including drug therapy, optimization of islet preparation process, islet engineering and Mesenchymal stem cells cotransplantation. We also expounded the heterogeneity, plasticity and activation mechanism of macrophages in islet transplantation, providing a theoretical basis for further research. [ABSTRACT FROM AUTHOR]

The gut microbiota (GM), as a forgotten organ, refers to the microbial community that resides in the gastrointestinal tract and plays a critical role in a variety of physiological activities in different body organs. The GM affects its targets through neurological, metabolic, immune, and endocrine pathways. The GM is a dynamic system for which exogenous and endogenous factors have negative or positive effects on its density and composition. Since the mid-twentieth century, laboratory animals are known as the major tools for preclinical research; however, each model has its own limitations. So far, two main models have been used to explore the effects of the GM under normal and abnormal conditions: the isolated germ-free and antibiotic-treated models. Both methods have strengths and weaknesses. In many fields of host-microbe interactions, research on these animal models are known as appropriate experimental subjects that enable investigators to directly assess the role of the microbiota on all features of physiology. These animal models present biological model systems to either study outcomes of the absence of microbes, or to verify the effects of colonization with specific and known microbial species. This paper reviews these current approaches and gives advantages and disadvantages of both models. [ABSTRACT FROM AUTHOR]

We have developed Convacell®—a COVID-19 vaccine based on the recombinant nucleocapsid (N) protein of SARS-CoV-2. This paper details Convacell's® combined phase I/II and IIb randomized, double-blind, interventional clinical trials. The primary endpoints were the frequency of adverse effects (AEs) and the titers of specific anti-N IgGs induced by the vaccination; secondary endpoints included the nature of the immune response. Convacell® demonstrated high safety in phase I with no severe AEs detected, 100% seroconversion by day 42 and high and sustained for 350 days anti-N IgG levels in phase II. Convacell® also demonstrated a fused cellular and humoral immune response. Phase IIb results showed significant post-vaccination increases in circulating anti-N IgG and N protein-specific IFNγ+-producing PBMC quantities among 438 volunteers. Convacell® showed same level of immunological efficacy for single and double dose vaccination regimens, including for elderly patients. The clinical studies indicate that Convacell® is safe and highly immunogenic. [ABSTRACT FROM AUTHOR]

Impairment of fish growth and immune system due to stress and disease are major constraints in aquaculture industry. Traditionally, antibiotic was used as prophylactic agent in the health management of aquaculture species. However, antibiotic only provide a temporary solution to the problem of disease outbreak. Over-reliance on antibiotic also has led to the increasing cases of antibiotic resistance among pathogenic bacteria from aquaculture sites and contamination of antibiotic residues into human food chain. Probiotic, prebiotic and symbiotic are therefore suggested as alternatives to prophylactic antibiotic to be used in the aquaculture industry. A potential prophylactic agent is polysaccharide that could be developed into an alternative antibiotic for aquatic animals. In this review paper, definition, sources, and mode of action of polysaccharide are presented. The roles of polysaccharides in fish farming with emphasis on growth improvement, immune system enhancement, disease resistance stimulation in tilapia farming, and the effects of polysaccharides on abiotic stressors are summarized and discussed. [ABSTRACT FROM AUTHOR]

Aquaculture industry contributes significant aquaculture species production to meet fish protein demand from the world. The industry is gearing towards intensification to increase more production in the near future. Various technologies and efforts were introduced into aquaculture industry to bring it up to the next higher level. However, the development of aquaculture industry is hindered by disease constraint. As a result, excessive use of antibiotics and chemicals were applied to reduce or minimize risk of disease outbreak in aquaculture farming activity. Subsequently, aquacultures products and environment were highly exposed to these antibiotics and chemicals. To resolve this issue, fish farmers were encouraged to utilize alternative method in aquaculture species health management. Prebiotics has become a new approach in aquaculture industry to maintain aquaculture species health and a good environment at the same time produce chemical and antibiotic-free aquaculture product. In this review paper, we summarize and discuss the effects of prebiotic mixtures administration on growth performance, immune response, disease resistance, and tolerance against abiotic stressors of aquatic animals. [ABSTRACT FROM AUTHOR]

To explore the impacts of pulse vaccination on the dynamical behaviors of virus, the current paper investigates the persistence and global attractivity of a diffusive viral infection model incorporated with impulsive CTL immune response while the stronger logistic growth mechanism. Based on the comparison principle and the proper upper and lower solutions, we first discuss the existence of the infection-free steady state, and define the crucial CTL-activated viral infection reproduction number $ R_0 $ R 0 . Then, the fundamental extinction and uniform persistence behaviors of virus are distinguished by various cases of the threshold parameter $ R_0 $ R 0 . Finally, the existence and global attractivity of the positive steady state are still established by employing Brouwer's fixed point theorem and auxiliary functional. Our results indicate that high vaccination rates will stimulate the CTL response more effectively, and thus eventually can force the virus to eradicate. [ABSTRACT FROM AUTHOR]

Helminths are multicellular parasites that are a substantial problem for both human and veterinary medicine. According to estimates, 1.5 billion people suffer from their infection, resulting in decreased life quality and burdens for healthcare systems. On the other hand, these infections may alleviate autoimmune diseases and allergy symptoms. The immune system is programmed to combat infections; nevertheless, its effector mechanisms may result in immunopathologies and exacerbate clinical symptoms. This review summarizes the role of the immune response against worms, with an emphasis on the Th2 response, which is a hallmark of helminth infections. We characterize non-immune cells (enteric tuft cells—ETCs) responsible for detecting parasites, as well as the role of hematopoietic-derived cells (macrophages, basophils, eosinophils, neutrophils, innate lymphoid cells group 2—ILC2s, mast cells, T cells, and B cells) in initiating and sustaining the immune response, as well as the functions they play in granulomas. The aim of this paper is to review the existing knowledge regarding the immune response against helminths, to attempt to decipher the interactions between cells engaged in the response, and to indicate the gaps in the current knowledge. [ABSTRACT FROM AUTHOR]

The major histocompatibility complexes of vertebrates play a key role in the immune response. Antigen-presenting cells are loaded on MHC I molecules, which mainly present endogenous antigens; when MHC I presents exogenous antigens, this is called cross-presentation. The discovery of cross-presentation provides an important theoretical basis for the study of exogenous antigens. Cross-presentation is a complex process in which MHC I molecules present antigens to the cell surface to activate CD8+ T lymphocytes. The process of cross-representation includes many components, and this article briefly outlines the origins and development of MHC molecules, gene structures, functions, and their classical presentation pathways. The cross-presentation pathways of MHC I molecules, the cell lines that support cross-presentation, and the mechanisms of MHC I molecular transporting are all reviewed. After more than 40 years of research, the specific mechanism of cross-presentation is still unclear. In this paper, we summarize cross-presentation and anticipate the research and development prospects for cross-presentation. [ABSTRACT FROM AUTHOR]

Leishmaniasis is a widespread but still underdiagnosed parasitic disease that affects both humans and animals. There are at least 20 pathogenic species of Leishmania, most of them being zoonotic. The diagnosis of leishmaniasis remains a major challenge, with an important role being played by the species of parasites involved, the genetic background, the immunocompetence of the host. This paper brings to the fore the sensitivity of the balance in canine and human leishmaniasis and addresses the importance of the host's immune response in establishing a correct diagnosis, especially in certain cases of asymptomatic leishmaniasis, or in the situation the host is immunosuppressed or acquired leishmaniasis through vertical transmission. The methods considered as a reference in the diagnosis of leishmaniasis no longer present certainty, the diagnosis being influenced mostly by the immune response of the host, which differs according to the presence of other associated diseases or even according to the breed in dogs. Consequently, the diagnosis and surveillance of leishmaniasis cases remains an open topic, requiring new diagnostic methods adapted to the immunological state of the host. [ABSTRACT FROM AUTHOR]

Immunotherapy is a therapeutic approach that employs immunological principles and techniques to enhance and amplify the body's immune response, thereby eradicating tumor cells. Immunotherapy has demonstrated effective antitumor effects on a variety of malignant tumors. However, when applied to humans, many immunotherapy drugs fail to target lesions with precision, leading to an array of adverse immune-related reactions that profoundly limit the clinical application of immunotherapy. Nanodrug delivery systems enable the precise delivery of immunotherapeutic drugs to targeted tissues or specific immune cells, enhancing the immune antitumor effect while reducing the number of adverse reactions. A nanodrug delivery system provides a feasible strategy for activating the antitumor immune response by the following mechanisms: 1) increased targeting and uptake of vaccines by DCs, which enhances the efficacy of the immune response; 2) increased tumor cell immunogenicity; 3) regulation of TAMs and other cells by, for example, regulating the polarization of TAMs and interfering with TAN formation, and ECM remodeling by CAFs; and 4) interference with tumor immune escape signaling pathways, namely, the PD-1/PD-L1, FGL1/LAG-3 and IDO signaling pathways. This paper reviews the progress of nanodrug delivery system research with respect to tumor immunotherapy based on tumor immunomodulation over the last few years, discussing the promising future of these delivery systems under this domain. [ABSTRACT FROM AUTHOR]

Vitamin A, a critical micronutrient, plays a vital role in maintaining poultry health and maximizing productivity. This comprehensive review paper conducts a thorough analysis of the consequences of vitamin A deficiency in domestic fowl. It delves into the physiological functions of vitamin A and investigates how hypovitaminosis A impacts growth, immune function, reproduction, and overall poultry performance. Additionally, the review explores effective strategies for preventing and managing vitamin A deficiency, such as dietary adjustments and supplementation, while addressing the specific requirements for vitamin A intake. The implementation of these strategies holds immense importance in optimizing poultry management practices and achieving peak performance in poultry production. A profound understanding of the prevalence and factors contributing to clinical and subclinical vitamin A deficiency in domestic fowl is essential for ensuring the efficiency of poultry farming operations. Recognizing the pivotal role of vitamin A and applying the appropriate measures empowers poultry farmers to enhance the health outcomes and overall performance of their flocks. [ABSTRACT FROM AUTHOR]

Creating an effective and safe vaccine is critical to fighting the coronavirus infection successfully. Several types of COVID-19 vaccines exist, including inactivated, live attenuated, recombinant, synthetic peptide, virus-like particle-based, DNA and mRNA-based, and sub-unit vaccines containing purified immunogenic viral proteins. However, the scale and speed at which COVID-19 is spreading demonstrate a global public demand for an effective prophylaxis that must be supplied more. The developed products promise a bright future for SARS-CoV-2 prevention; however, evidence of safety and immunogenicity is mandatory before any vaccine can be produced. In this paper, we report on the results of our work examining the safety, toxicity, immunizing dose choice, and immunogenicity of QazCoVac-P, a Kazakhstan-made sub-unit vaccine for COVID-19. First, we looked into the product's safety profile by assessing its pyrogenicity in vaccinated rabbit models and using the LAL (limulus amebocyte lysate) test. We examined the vaccine's acute and sub-chronic toxicity on BALB/c mice and rats. The vaccine did not cause clinically significant toxicity-related changes or symptoms in our toxicity experiments. Finally, we performed a double immunization of mice, ferrets, Syrian hamsters, and rhesus macaques (Macaca mulatta). We used ELISA to measure antibody titers with the maximum mean geometric titer of antibodies in the animals' blood sera totaling approximately 8 log2. The results of this and other studies warrant recommending the QazCoVac-P vaccine for clinical trials. [ABSTRACT FROM AUTHOR]