The intestinal microbiota, comprised of bacteria, archaea, and phages, inhabits the gastrointestinal tract of the organism. Male reproductive sterility is currently a prominent topic in medical research. Increasing research suggests that gut microbiota dysbiosis can result in various reproductive health problems. This article specifically investigates the impact of gut microbiota dysbiosis on male reproductive infertility development. Gut microbiota imbalances can disrupt the immune system and immune cell metabolism, affecting testicular growth and sperm production. This dysfunction can compromise the levels of hormones produced and secreted by the endocrine glands, affecting male reproductive health. Furthermore, imbalance of the gut microbiota can disrupt the gut-brain-reproductive axis, resulting in male reproductive infertility. This article will explore how the imbalance of the gut microbiota impacts male reproductive infertility through immune regulation, endocrine regulation, and interactions of the gut-brain-reproductive axis, concluding with recommendations for prevention and treatment.

Maternal obesity and over/undernutrition can have a long-lasting impact on offspring health during critical periods in the first 1000 days of life. Children born to mothers with obesity have reduced immune responses to stimuli which increase susceptibility to infections. Recently, maternal western-style diets (WSD), high in fat and simple sugars, have been associated with skewing neonatal immune cell development, and recent evidence suggests that dysregulation of innate immunity in early life has long-term consequences on metabolic diseases and behavioral disorders in later life. Several factors contribute to abnormal innate immune tolerance or trained immunity, including changes in gut microbiota, metabolites, and epigenetic modifications. Critical knowledge gaps remain regarding the mechanisms whereby these factors impact fetal and postnatal immune cell development, especially in precursor stem cells in bone marrow and fetal liver. Components of the maternal microbiota that are transferred from mothers consuming a WSD to their offspring are understudied and identifying cause and effect on neonatal innate and adaptive immune development needs to be refined. Tools including single-cell RNA-sequencing, epigenetic analysis, and spatial location of specific immune cells in liver and bone marrow are critical for understanding immune system programming. Considering the vital role of immune function plays in offspring health, it will be important to understand how maternal diets can control developmental programming of innate and adaptive immunity.

Cancer remains one of the main causes of death in the world due to its increasing incidence and treatment difficulties. Although several progresses have been done in this field, innovative approaches are needed to reduce tumor incidence, progression and spreading. In particular, the development of cancer vaccines is currently ongoing like both preventive and therapeutic strategy. This concept is not new, but few vaccines have been approved in oncology. Antigen-based vaccination emerges as a promising strategy, leveraging specific tumor antigens to activate the immune system response. However, challenges persist in finding suitable delivery systems and antigen preparation methods. Exosomes (EXs) are highly heterogeneous bilayered vesicles which carry several molecule types in the extracellular space. The peculiarity is that they may be released from different cells and may be able to induce a direct or indirect stimulation of immune system. In particular, EX-based vaccines may cause anti-tumor immune attack or produce memory cells recognizing cancer antigens and inhibit disease appearance. This review delves into EXs composition, biogenesis, and immune-modulating properties exploring their role as tool for prevention and therapy in solid tumors. Finally, here we describe future research directions to optimize vaccine efficacy and realize the full potential of EX-based cancer immunotherapy.

Mastitis-causing bacteria can establish persistent infections in the mammary gland of commercially important dairy animals despite the presence of strong specific humoral and cellular immune mechanisms. The aim of this study was to encapsulate vitamin D3 by complex coacervation with sulfur-saturated bovine lactoferrin-alginate using microbial transglutaminase-catalyzed crosslinking and investigate the oral administration of encapsulated vitamin D3 in blood serum biomarkers of the immune response in late-lactating dairy goats. Dairy goats (n = 18) in late lactation were randomly assigned to three experimental groups (n = 6), after balancing weight. Dairy goats were orally administered with 0.35 mg vitamin D3/day in the unencapsulated form and 0.35 mg vitamin D3/day in the encapsulated powder form. Another group received the basal diet. The experimental period lasted 6 weeks. The blood serum concentrations of 25-hydroxyvitamin D3 [25-(OH)-D3], lactoferrin, immunoglobulin A (IgA), and interferon-gamma (INF-γ) were measured. The delivery of vitamin D3 to dairy goats resulted in a marked increase of 25-(OH)-D3 concentration in serum while the serum level of lactoferrin also increased. Alternatively, the serum levels of IgA and the immunomodulatory cytokine INF-γ were elevated following supplementation with the encapsulated vitamin D3. Overall, the capsules in the powder form used in this study kept vitamin D3 highly bioavailable.

During the coronavirus disease 2019 (COVID-19) pandemic, individuals with immune-mediated inflammatory diseases (IMIDs), such as systemic lupus erythematosus and rheumatoid arthritis, face a heightened risk of infection and severe outcomes due to immunological alterations resulting from their underlying conditions and immunosuppressive treatments. Even as the pandemic has transitioned to an endemic state, it remains crucial to recognize that these patients continue to be at risk. In this narrative review, we analyzed existing literature to explore the impact of IMIDs, clinical risk factors, and the influence of immunosuppressive therapies on COVID-19-related risks and outcomes. Notably, certain disease-modifying antirheumatic drugs (DMARDs), like rituximab, are associated with worse COVID-19 outcomes, and rituximab-treated patients show impaired immune responses to COVID-19 vaccination. Additionally, we outline the diverse effects of glucocorticoids on COVID-19 outcomes and management. To highlight real-life challenges faced by clinicians caring for patients with IMIDs, we present an illustrative scenario that underscores the importance of effective vaccination, timely boosting, and additional mitigation strategies against COVID-19. Given the clinical heterogeneity and diverse disease states within IMIDs, it is crucial to understand the ongoing implications and risks associated with COVID-19 in these patients, to guide the implementation of appropriate measures and optimize care and outcomes in the current endemic era.

In breast cancer, epithelial-mesenchymal transition (EMT) is positively associated with programmed death ligand 1 (PD-L1) expression and immune escape, and TWIST1 induces EMT and cancer metastasis. However, how TWIST1 regulates PD-L1 and immune evasion is unknown. This study analyzed TWIST1 and PD-L1 expression in breast cancers, investigated the mechanism for TWIST1 to regulate PD-L1 transcription, and assessed the effects of TWIST1 and PD-L1 in cancer cells on the cytotoxicity of CD8+ effector T cells. Interestingly, TWIST1 expression is associated with high-level PD-L1 in triple negative breast cancers (TNBCs). Overexpression and knockdown of TWIST1 robustly upregulates and downregulate PD-L1 expression, respectively. TWIST1 binds to the PD-L1 promoter and recruits the TIP60 acetyltransferase complex in a BRD8-dependent manner to promote PD-L1 expression, which drives immune escape of breast cancer cells by accelerating the exhaustion of CD8+ T cells. Accordingly, knockdown of TWIST1 or BRD8 or blockade of PD-L1 with a PD-L1 antibody significantly enhances CD8+ T cells to inhibit breast cancer cell growth. These results demonstrate that TWIST1 directly induces PD-L1 expression in breast cancer cells to drive immune evasion. Targeting TWIST1, BRD8 or PD-L1 in TNBC should facilitate CD8+ T cell-mediated immune therapy. TWIST1 may also serve as a biomarker for anti-PD-L1 immunotherapy.

Immune checkpoint inhibitors (ICI) are a promising form of immunotherapy that has significantly changed the therapeutic landscape for many advanced cancers. They have shown unique clinical benefit against a broad range of tumour types and a strong overall impact on survival in studied patient populations. However, there are still many limitations holding back this immunotherapy from reaching its full potential as a possible curative option for advanced cancer patients. A great deal of research is being undertaken in the hope of driving advancements in this area, building a better understanding of the mechanisms behind immune checkpoint inhibition and ultimately developing more effective, safer, and wider-reaching agents. Taking into account the current literature on this topic, this review aims to explore in depth the basis of the use of ICIs in the treatment of advanced cancers, evaluate its efficacy and safety, consider its current limitations, and finally reflect on what the future holds for this very promising form of cancer immunotherapy.

Gestational Diabetes Mellitus (GDM) is related with adverse outcomes for both the mother and the offspring. Immune and senescence play a crucial role in GDM progression. This study aims to explore the diagnostic significance of immune-related senescence (IRS) genes in GDM. We used weighted gene co-expression network analysis (WGCNA) and single sample gene set enrichment analysis (ssGSEA) to compute the immune score and aging score in control and GDM samples. Machine learning identified core IRS genes. Then we performed unsupervised cluster analysis in GDM patients to explore immune infiltration. Finally, we validated the core genes in clinical samples. We used the intersection of MEblack module from WGCNA and differentially expressed genes (DEGs) to obtain the potential genes. Next, a univariate logistic regression model including 23 potential genes were constructed, and these genes were filtered by least absolute shrinkage and selection operator (LASSO) algorithm. There were 5 potential genes (COX17, RRAS2, RRAGC, CECR1, and TACC2), which defined as biomarkers, remained eventually, and the efficacy of these biomarkers was evaluated by nomogram. Finally, the results from both qRT-PCR and western blot analyses demonstrated CECR1 was down-regulated, while TACC2 was up-regulated in GDM placental tissue. Our study identified CECR1 and TACC2 as diagnostic biomarkers for GDM associating with immune and senescence, providing a new perspective on GDM progression.

Diabetes mellitus (DM) poses a significant challenge to global health, with its prevalence projected to rise dramatically by 2045. This narrative review explores the bidirectional relationship between periodontitis (PD) and type 1 diabetes mellitus (T1DM), focusing on cellular and molecular mechanisms derived by the interplay between oral microbiota and the host immune response. A comprehensive search of literature published between 2008 and 2023 was conducted to elucidate the association between these two diseases. Preclinical and clinical evidence suggests a bidirectional relationship, with individuals with T1DM exhibiting heightened susceptibility to periodontitis, and vice versa. The review includes recent findings from human clinical studies, revealing variations in oral microbiota composition in T1DM patients, including increases in certain pathogenic species such as Porphyromonas gingivalis, Prevotella intermedia, and Aggregatibacter actinomycetemcomitans, along with shifts in microbial diversity and abundance. Molecular mechanisms underlying this association involve oxidative stress and dysregulated host immune responses, mediated by inflammatory cytokines such as IL-6, IL-8, and MMPs. Furthermore, disruptions in bone turnover markers, such as RANKL and OPG, contribute to periodontal complications in T1DM patients. While preventive measures to manage periodontal complications in T1DM patients may improve overall health outcomes, further research is needed to understand the intricate interactions between oral microbiota, host response, periodontal disease, and systemic health in this population.

Pancreatic cancer (PC) has a poor prognosis and displays resistance to immunotherapy. A better understanding of tumor-derived extracellular vesicles (EVs) effects on immune responses might contribute to improved immunotherapy. EVs derived from Capan-2 and BxPC-3 PC cells isolated by ultracentrifugation were characterized by atomic force microscopy, western blot (WB), nanoparticle tracking analysis and label-free proteomics. Fresh PBMCs from healthy donors were treated with PC- or control-derived heterologous EVs followed by flow cytometry analysis of CD8+ and CD4+ lymphocytes. Proteomics of lymphocytes sorted from EV-treated, or -untreated PBMCs was performed and IFN-γ concentration was measured by ELISA. Notably, most of the proteins identified in Capan-2 and BxPC-3 EVs by proteomic analysis were connected in a single functional network (p=1x10-16) and were involved in “Immune System” (FDR: 1.10x10-24 and 3.69x10-19, respectively). Interestingly, treatment of healthy donor-derived PBMCs with Capan-2 EVs, but not with BxPC-3 EVs or heterologous control EVs induced early activation of CD8+ and CD4+ lymphocytes. Proteomics of lymphocytes sorted from EV-treated PBMCs was consistent with their activation by Capan-2 EVs, indicating IFN-γ among major upstream regulators, as confirmed by ELISA. Proteomic and functional analyses indicate that PC-EVs have pleiotropic effects, and some may activate early immune response, which might be relevant for the development of highly needed immunotherapeutic strategies in this immune-cold tumor.

Cancer-associated cachexia (CAC) is a debilitating condition marked by muscle and fat loss, unresponsive to nutritional support, and contributes significantly to morbidity and mortality in patients with cancer. Immune dysfunction, driven by cytokine imbalance, contributes to CAC progression. This review explores the potential relationship between CAC and anti-cancer immune response in pre-clinical and clinical studies. Pre-clinical studies showcase the involvement of cytokines like IL-1β, IL-6, IL-8, IFN-γ, TNF-α, and TGF-β, in CAC. IL-6 and TNF-α, interacting with muscle and adipose tissues, induce wasting through JAK/STAT and NF-κB pathways. Myeloid-derived suppressor cells (MDSCs) exacerbate CAC by promoting inflammation. Clinical studies confirm elevated pro-inflammatory cytokines (IL-6, IL-8, TNFα) and immune markers like neutrophil-to-lymphocyte ratio (NLR) in patients with CAC. Thus, immunomodulatory mechanisms involved in CAC may impact the anti-neoplastic immune response. Inhibiting CAC mechanisms could enhance anti-cancer therapies, notably immunotherapy. R-ketorolac, a new immunomodulator, reversed weight loss and increased survival in mice. Combining these agents with immunotherapy may benefit patients with cancer experiencing CAC. Further research is vital to understand the complex interplay between tumor-induced immune dysregulation and CAC during immunotherapy.

The emotion of disgust protects individuals against pathogens, and it has been found that during pregnancy, it is elevated. Physiological mechanisms discussed in relation to these changes include immune markers and progesterone levels. The aim of this study is to assess the association between steroids and disgust in pregnancy. In a sample of 179 pregnant women, we have analyzed blood serum steroid concentrations and measured disgust sensitivity by text-based questionnaires in the first and third trimester. We found positive correlations between disgust sensitivity and the levels of C19 steroids, including testosterone, but also its precursors in the Δ5 pathway (androstenediol, DHEA, and their sulfates) and the Δ4 pathway (androstenedione). Furthermore, positive correlations between disgust sensitivity and 5α/β-reduced C19 steroid metabolites were consistently present in both trimesters. In the first trimester, we found a positive association between disgust sensitivity and 17-hydroxypregnanolone as well as some estrogens. In the third trimester, we have observed positive associations between disgust sensitivity and cortisol as well as immunoprotective Δ5 C19 7α/β-hydroxy-steroids. Our study has thus shown that disgust sensitivity is positively correlated with immunomodulatory steroids, and in the third trimester, steroids may reflect potential maternal anxiety-related symptoms.

Huanglongbing (HLB), or citrus greening, is a devastating disease impacting citrus trees worldwide, with severe effects particularly noted in Florida. Current strategies to combat HLB have focused on aggressive replanting despite the high susceptibility of young trees to infection. In this context, it is critical to explore agronomic practices that can enhance the health and resistance of young citrus trees to HLB. Here, we demonstrate that treatment with homobrassinolide (HBr), a type of brassinosteroid, on newly planted citrus trees can delay HLB infection and improve tree health amidst the high psyllid pressure conditions endemic to Florida. Our study reveals a significant reduction in HLB infection rates in HBr-treated trees compared to control trees, with only 25% of treated trees testing positive for HLB by six months, in contrast to 100% infection in untreated trees. This delay in infection may be attributed to HBr inducing an immune response and negatively impacting psyllid performance, as subsequently demonstrated in a greenhouse experiment. Our findings suggest that HBr applications could serve as a viable strategy to enhance the resilience of citrus production against HLB, underscoring the need for further investigation into their mechanisms of action and potential role in a comprehensive pest and disease management strategy.

Probiotics play an important role as immunostimulants in improving growth and health status in fish. However, little is known on the effects of probiotics when fish offered a low fish meal diet. This study evaluated the effects of three probiotic bacteria isolated from the fish intestine to replace antibiotics in a reduced fish meal diet fed to the juvenile olive flounder Paralichthys olivaceus. A basal diet without feed additives was used as a control (CON) and five other diets were formulated by supplementation with Bacillus subtilis WB60 (BSWB60) at 1×108 CFU/g, B. subtilis SJ10 (BSSJ10) at 1×108 CFU/g, Enterococcus faecium SH30 (EFSH30) at 1×107 CFU/g, amoxicillin (AMO) at 4 g/kg and oxytetracycline (OTC) at 4 g/kg of the basal diet. Triplicate groups of 25 fish averaging 12.1±0.09 g (mean±SD) were fed one of the six experimental diet groups for 8 weeks. Then, 45 fish from each group were intraperitoneally injected with the pathogenic bacteria, Edwardsiella tarda, and mortality was recorded for 14 days. At the end of the feeding trial, weight gain, specific growth rate and feed efficiency of fish fed the BSWB60 diet were significantly greater than those of fish fed the CON, OTC and AMO diets (P < 0.05). Furthermore, feeding efficiency and protein efficiency ratio of fish fed the BSWB60 diet were significantly greater than those of fish fed the CON, OTC and AMO diets. However, there were no significant differences in survival, hepatosomatic indices, viscerosomatic indices and condition factors among the fish fed the experimental diets. The whole-body proximate composition of the fish was unaffected by the dietary treatments. The serum biochemistry parameters, such as aspartate aminotransferase levels were significantly greater in fish fed the BSSJ10 diet than in those fed the BSWB60 diet. However, serum alanine aminotransferase, glucose and total protein levels were not significantly affected by the experimental diets. The lysozyme activity of fish fed the BSSJ10, BSWB60 and EFSH30 diets was significantly greater than that of the CON, OTC and AMO diets. The myeloperoxidase activity of fish fed the BSWB60 diet was significantly greater than that of the fish fed the CON and AMO diets. The flounder growth hormone levels of fish fed the BSSJ10, BSWB60, EFSH30 and AMO diets were significantly greater than that of the fish fed the CON diet. The interleukin 1β (IL-1β) gene expression levels in fish fed the BSSJ10 and EFSH30 diets were significantly greater than those in fish fed the CON, OTC and AMO diets. The interleukin 10 (IL-10) gene expression levels in fish fed the BSSJ10, BSWB60, EFSH30 and OTC diets were significantly greater than those of fish fed the CON and AMO diets. Intestinal histology revealed that the average villus length of fish fed the BSSJ10, BSWB60, and EFSH30 diets was significantly greater than that of fish fed the CON, OTC and AMO diets. The cumulative survival rates of fish fed the EFSH30 and BSWB60 diets were significantly greater than those of fish fed the CON diet after the 15th day of the challenge test. Overall, the results of the present study demonstrated that the supplementation of autochthonous bacteria, B. subtilis (108 CFU/g diet) or E. faecium (107 CFU/g diet) in the diet could be ideal probiotics to replace antibiotics based on growth performance, the serum biochemical composition, immune responses and disease resistance in olive flounder fed a low fish meal diet..

In this article, we consider the relationship between the brain and the immune system in the context of the Orch OR (Orchestrated Objective Reduction) theory of consciousness. Orch OR is a theory that postulates that consciousness arises from quantum computations occurring inside microtubules. The immune system is capable of acquiring, learning, and remembering information, thus showing all the attributes of natural intelligence. We argue that the immune system also has the attribute of consciousness and can gain access to an amount of information greater than what is accessible to the brain since it is not constrained by brain's reducing valve that is responsible for cognitive bottlenecks. We also describe the role of meditation and religious chanting in affecting the brain and immune system. We speculate that some effects of religious chanting on the immune system may not be mediated by the brain. Finally, we examine the role of the immune system in connecting with the consciousness embedded in the universe.

Viral co-infections, where a host is infected by multiple viruses simultaneously, are common in the human population. Human viral co-infections can lead to complex interactions between viruses and the host immune system, affecting the clinical outcome and posing challenges for treatment. Understanding the types, mechanisms, impacts, and identification methods of human viral co-infections is crucial for the prevention and control of viral diseases. In this review, we first introduce the significance of studying human viral co-infections and summarize the current research progress and gaps in this field. We then classify human viral co-infections into four types based on the pathogenic properties and species of the viruses involved. Next, we discuss the molecular mechanisms of viral co-infections, focusing on virus-virus interactions, host immune responses, and clinical manifestations. We also summarize the experimental and computational methods for identifying viral co-infections, emphasizing the latest advances in high-throughput sequencing and bioinformatics approaches. Finally, we highlight the challenges and future directions in human viral co-infection research, aiming to provide new insights and strategies for the prevention, control, diagnosis, and treatment of viral diseases. This review provides a comprehensive overview of the current knowledge and future perspectives on human viral co-infections, and underscores the need for interdisciplinary collaborations to address this complex and important topic.

Fermented foods and ingredients, including fermentates derived from lactic acid bacteria (LAB) in dairy products, can modulate the immune system. Here we describe the use of reconstituted skimmed milk powder to generate novel fermentates from Lactobacillus helveticus strains SC232, SC234, SC212, and SC210, and from Lacticaseibacillus casei strains SC209 and SC229, and demonstrate using in vitro assays that these fermentates can differentially modulate cytokine secretion by bone marrow derived dendritic cells (BMDCs) when activated with either the viral ligand, loxoribine, or an inflammatory stimulus, lipopolysaccharide. Specifically, we demonstrate that SC232 and SC234 increase cytokines IL-6, TNF-α, IL-12p40, IL-23, IL-27 and IL-10, and decreased IL-1β in primary bone marrow derived dendritic cell (BMDCs) stimulated with a viral ligand. In contrast exposure of these cells to SC212 and SC210 resulted in increased IL-10, IL-1β, IL-23, and decreased IL-12p40 following activation of the cells with the inflammatory stimulus LPS. Interestingly SC209 and SC229 had little or no effect on cytokine secretion by BMDCs. Overall, our data demonstrates that these novel fermentates have specific effects and can differentially enhance key immune mechanisms that are critical to viral immune responses, or can suppress responses involved in chronic inflammatory conditions, such as Ulcerative Colitis (UC), and Crohn’s disease (CD).

Cystatin F (CstF) is a protease inhibitor of cysteine cathepsins, including those involved in acti-vating the perforin/granzyme cytotoxic pathways. It is targeted to the endolysosomal pathway but can also be secreted to the extracellular milieu or endocytosed by bystander cells. CtsF was shown to be significantly increased in tuberculous pleurisy, and during HIV coinfection, pleural fluids display high viral loads. In human macrophages, we revealed a strong upregulation of CstF during infection with Mycobacterium tuberculosis (Mtb). CstF manipulation using RNA si-lencing led to increased proteolytic activity of lysosomal cathepsins, improving Mtb intracellular killing. Here, we investigate the impact of CstF depletion during coinfection of Mtb-infected mac-rophages with lymphocytes infected with HIV. Our results indicate that decreasing CstF released by phagocytes impacts the major pro-granzyme convertase cathepsin C of cytotoxic immune cells. Consequently, an observed increase of the granzyme B apoptotic effects leads to a significant re-duction in viral replication in HIV-infected lymphocytes. Overall, our results indicate a mecha-nism of Mtb/HIV evasion of the cytotoxic mediated pathogen killing driven by the ax-is CstF/ catC/granzymes contributing to this syndemic interaction. Ultimately, this knowledge can be crucial for developing new therapeutic approaches to control both pathogens based on manipulating CstF.

Abstract: Lipidic carriers employed for the entrapment, encapsulation and precise targeting the bioactive compounds offer significant advantages to the biomedical, pharmaceutical, nutraceutical and cosmeceutical industries. These lipid and phospholipid-based vesicles can improve the solubility, permeation, pharmacokinetics, pharmacodynamics and bioavailability of the encapsulated material. As a matter of fact, nano-sized phospholipid vesicles have attained the highest success rate in commercialization among the available drug encapsulation technologies. Nevertheless, developing industrially acceptable products still remains a challenge. Among the main disadvantages of conventional lipidic carriers are their instability in the biological environments, and their sensitivity to changes in the pH, temperature and enzymes. To overcome these problems, the new generation of phospho/lipid-based carrier systems was developed using ingredients from microorganisms living in extremely harsh environments (i.e., archeaeobacteria). The present entry aims to review unique features of archaeolipids and recent developments in their application for the encapsulation of genetic material as well as their role and function as adjuvants and vaccine candidates.

Background: Glucose 6-phosphate dehydrogenase (G6PD) deficiency increases the risk of neonatal hyperbilirubinemia. The aim of the study is to evaluate the clinical findings of glucose 6 phosphate dehydrogenase (G6PD) and pyruvate kinase (PK) deficiency, to prevent further examinations for prolonged jaundice, and to contribute by regulating its treatment. At the same time, it is to determine whether systemic-immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) can be used in addition to conventional complete blood count (CBC) parameters in the diagnosis of neonatal prolonged jaundice. Methods: In full term neonates with hyperbilirubinemia who were admitted to Medicine Hospital between January 2019 and January 2024 with the complaint of jaundice, 167 infants with a serum bilirubin level above 5 mg/dL, whose jaundice persisted after the 10th day, were included in the study. Results: 63.5% of the patients were male and the mean age was 31±6 days. G6PD was negatively perfectly correlated with NLR (r: -1; p

Fowlpox virus (FPV) has been used as a vector for many years. To date, surprisingly, very little data exist on the persistence of fowlpox vaccines in chicken tissues, or what kind of immune cells respond to the vaccination at the site of inoculation. Although both humoral and cellular mediated immunity (CMI) play a part in overall immunity against FPV, little is known regarding the cell-mediated immune responses to FPV infection. The main aim of this paper was to measure persistence of the recombinant fowlpox vaccine in the skin tissues following vaccination. The results showed that the recombinant FPVs do not persist for long, and are cleared by 6 days post-vaccination (dpv). The response of immune cells (macrophages, B cells, CD4+ and CD8+ T cells) that infiltrating the site of vaccination was estimated.

Hypertensive disorders of pregnancy (HDP), including preeclampsia (PE) and gestational hypertension (GH), are major causes of maternal and fetal morbidity and mortality. This review elucidates the role of regulatory T cells (Tregs) in the immunological aspects of HDP and explores their therapeutic potential. Tregs, known for maintaining immune tolerance, are crucial in pregnancy to prevent immune-mediated rejection of the fetus. In HDP, Treg numbers and function imbalance are observed, correlating with disease severity. The review highlights that Tregs contribute to immunological adaptation in normal pregnancy, ensuring fetal acceptance and placental development. In contrast, HDP is associated with Treg dysfunction, marked by decreased numbers and impaired regulatory capacity, leading to inadequate immune tolerance and abnormal placental development. This dysfunction is particularly evident in PE, where Tregs fail to adequately modulate the maternal immune response against fetal antigens, contributing to the pathophysiology of the disorder. Therapeutic interventions aiming to modulate Treg activity represent a promising avenue for HDP management. Studies in animal models and limited clinical trials suggest that enhancing Treg functionality could mitigate HDP symptoms and improve pregnancy outcomes. However, the review acknowledges the complexity of translating these findings into effective clinical therapies, given the multifactorial nature of HDP and the intricate regulatory mechanisms of Tregs. In conclusion, while the precise role of Tregs in HDP is still being unravelled, their central role in immune regulation during pregnancy is indisputable. Further research is needed to fully understand the mechanisms by which Tregs contribute to HDP and to develop targeted therapies that can safely and effectively harness their regulatory potential for treating hypertensive diseases of pregnancy.

Fermented foods have long been known to have immunomodulatory capabilities and fermentates derived from the lactic acid bacteria of dairy products can modulate the immune system. We have used skimmed milk powder to generate novel fermentates using Lb. helveticus strains SC234 and SC232 and we demonstrate here that these fermentates can enhance key immune mechanisms that are critical to the immune response to viruses. We show that our novel fermentates SC234 and SC232 can positively impact on cytokine and chemokine secretion, nitric oxide (NO) production, cell surface marker expression, and phagocytosis in macrophage models. We demonstrate that fermentates SC234 and SC232 increase the secretion of cytokines IL-1β, IL-6, TNF-α, IL-27, and IL-10, promote an M1 proinflammatory phenotype for viral immunity via NO induction, decreases chemokine expression of Monocyte Chemoattractant Protein (MCP), increasing cell surface marker expression, and enhance phagocytosis in comparison to their starting material. These data suggest that these novel fermentates have potential as novel functional food ingredients for the treatment, management and control of viral infection.

Antler is the fastest growing tissue. Because is based on proto-oncogenes, to avoid the risk of cancer, antlers evolved strong anticancer mechanisms, and thus its extract (DVA) is effective also against the few human tumours studied so far. We assessed whether DVA is a general anticancer compound testing direct effects in cells of different tumours: glioblastoma (GBM), colorectal and breast cancer, and leukaemia. DVA reduced viability of tumour but not healthy cells. Mobility decreased at least at the longest test (72 h). Intraperitoneal/oral 200 mg DVA/kg administration in GBM xenograft mice for 28 d reduced tumour weight 66.3% and 61.4% respectively, and also spleen weight. In addition, tumours treated with DVA showed symptoms of liquefactive necrosis. Serum cytokines showed DVA up-regulated factors related with tumour fighting and down-regulated those related with inducing immune tolerance to the tumour. DVA shows general anticancer effects in the lines tested and, in GBM mice, also strong indirect effects apparently mediated by the immune system.

Autoimmune kidney diseases arise from a loss of tolerance to antigens, often with unclear triggers. In this review we explore the role of the gut microbiome and how disease, diet and therapy can alter the gut microbiota consortium. Perturbations in the gut microbiota may induce the translocation of microbiota-derived inflammatory molecules such as liposaccharide (LPS) and other toxins systemically by penetrating the gut epithelial barrier. Once in the blood stream these pro-inflammatory mediators activate immune cells which release pro-inflammatory molecules many of which are antigens in autoimmune diseases. The ratio of gut bacteria Bacteroidetes:Firmicutes is associated with worse outcomes in multiple autoimmune kidney diseases including Lupus nephritis, MPO-ANCA vasculitis and Goodpasture’s syndrome. Therapies which enhance short chain fatty acid (SCFA)-producing bacteria in the gut have powerful therapeutic potential. Dietary fibre is fermented by gut bacteria which in turn release SCFAs which protect the gut barrier as well as modulate immune responses towards a tolerogenic anti-inflammatory state. Herein, we describe where the current field of research is and the strategies to harness the gut microbiome as potential therapy.

A number of studies suggested that influenza vaccination can provide protection against COVID-19 but the underlying mechanisms that could explain this association is still unclear. In this study, the effect of the 2021/2022 seasonal influenza vaccination on the immune response to the booster dose of anti-SARS-CoV-2 vaccination was evaluated in a cohort of healthy individuals. One hundred and thirteen participants were enrolled, and 74 of them with no prior COVID-19 diagnosis or significant co-morbidities were considered for the analysis. Participants received the anti-influenza tetravalent vaccine and the booster dose of the anti-SARS-CoV-2 vaccine or the anti-SARS-CoV-2 vaccine alone. Blood was collected before and 4 weeks after each vaccination and 12 weeks after SARSCoV2 vaccination and analyzed for anti-flu and anti-spike-specific antibody titers and for in vitro influenza and SARS-CoV-2 neutralization capacity. Results indicated an increased reactivity in subjects who received both influenza and SARSCoV2 vaccinations, as compared to those who received only the SARS-CoV-2 vaccine, with sustained anti-spike antibody titers up to 12 weeks post-vaccination. Immune response to influenza vaccine was evaluated and individuals were stratified as high or low responders. High responders showed increased antibody titers against SARSCoV2 vaccine both after 4- and 12-weeks post-vaccination. On the contrary, the individuals classified as low responders were less responsive to the SARS-CoV-2 vaccine. These data indicate that both external stimuli, such as influenza vaccination, and the host's intrinsic ability to respond to stimuli play a role in the response to vaccine.

With the rapid development of tumor immunotherapy, nanoparticle vaccines have attracted much attention as a potential therapeutic strategy. The potential role of the mannose-modified lipid calcium phosphate nanoparticle vaccine in enhancing the anti-tumor immune response was investigated. The aim of this study was to investigate the effect of mannose modification on the immune response of nanoparticles in regulating the tumor microenvironment through systematic review and analysis and to explore its potential clinical application in tumor therapy. Currently, despite the potential advantages of nanoparticle vaccines in immunotherapy, achieving an effective immune response in the tumor microenvironment remains a challenge. Tumor immune escape and overexpression of immunosuppressive factors limit its clinical application. Therefore, this study will explore how to intervene in the immunosuppressive mechanism in the tumor microenvironment through mannose-modified lipid calcium phosphate nanoparticle vaccines so as to improve the immunotherapy effect of tumor patients and provide new ideas and strategies for the field of tumor therapy.

The sheer number of gene variants and the extent of the observed clinical and molecular heterogeneity recorded in neuropsychiatric disorders (NPDs), could be due to the magnified downstream effects initiated by a smaller group of genomic higher order alterations in response to endogenous or environmental stress. Chromosomal common fragile sites (CFS) are functionally linked with microRNA’s, gene copy number variants (CNVs), sub-microscopic deletions and duplications of DNA, rare single-nucleotide variants (SNVs/SNPs) and small insertions/deletions (indels), as well as chromosomal translocations, gene duplications, altered methylation, microRNA and L1 transposon activity and 3-D chromosomal topology characteristics. These genomic structural features have been linked with various NPDs in mostly isolated reports, and have usually only been viewed as areas harboring potential candidate genes of interest. The suggestion to use a higher level entry point, (the ‘fragilome’ and associated features), activated by a central mechanism (‘stress’) for studying NPD genetics, has the potential to unify the existing vast number of different observations in this field. This approach may explain the continuum of gene findings distributed between affected and unaffected individuals, the clustering of NPD phenotypes and overlapping comorbidities, the extensive clinical and molecular heterogeneity and the association with certain other medical disorders.

Atherosclerosis, a complex metabolic-immune disease characterized by a chronic inflammation driven by the buildup of lipid-rich plaques within arterial walls, has emerged as a pivotal factor in the intricate interplay between cancer and cardiovascular disease. This bidirectional relationship, marked by shared risk factors and pathophysiological mechanisms, underscores the need for a comprehensive understanding of how these two formidable health challenges intersect and influence each other. Cancer and its treatments can contribute to the progression of atherosclerosis while atherosclerosis with its inflammatory microenvironment can exert profound effects on cancer development and outcomes. Both cancer and cardiovascular disease involve intricate interactions between general and personal exposomes. In this review we want to summarize the state-of-the-art of translational data and try to show how oncologic studies on cardiotoxicity can broaden our knowledge of crucial pathways in cardiovascular biology with a positive impact on precision cardiology and cardioncology.

Recently intraductal carcinoma of the prostate (IDCP) has attracted increasing interest owing to its unfavorable prognoses. To effectively identify the IDCP-specific gene expression profile, we took a novel approach of characterizing a typical IDCP case using spatial gene expression analysis. A formalin-fixed, paraffin-embedded sample was subjected to Visium CytAssist Spatial Gene Expression analysis. IDCP within invasive prostate cancer sites was recognized as a distinct cluster separate from other invasive cancer clusters. Highly expressed genes defining the IDCP cluster, such as MUC6, MYO16, NPY, and KLK12, reflected the aggressive nature of high-grade prostate cancer. IDCP sites also showed increased hypoxia markers HIF1A, BNIP3L, PDK1, and POGLUT1; decreased fibroblast markers COL1A2, DCN, and LUM; and decreased immune cell markers CCR5 and FCGR3A. Overall, these findings indicate that the hypoxic tumor microenvironment and reduced accessibility to immune cells, which reflect the pathological characteristics of IDCP, may influence the aggressiveness of high-grade prostate cancer.

Despite the recent availability of immune checkpoint inhibitors, not all patients affected by Non-Small Cell Lung Cancer (NSCLC) benefit from immunotherapy. The reason for this variability relies to a variety of factors which may allow the identification of novel biomarkers. Presently, a variety of biomarkers are under investigation, including the PD1/PDL1 axis, the tumor mutational burden, and the Microbiota. This latter is made by all bacteria and other microorganisms hosted in our body. The gut microbiota is the most represented and has been involved in different physiological and pathological events, including cancer. In this light, it appears that all conditions modifying gut microbiota can influence cancer, its treatment, and its treatment-related toxicities. The aim of this review is to analyze all conditions influencing the gut microbiota and, therefore, affecting response to immunotherapy, iRAEs and their management in NSCLC patients. The investigation of the landscape of these biological events can allow novel insights for optimal management of NSCLC immunotherapy.

Background: In recent years, whole blood parameters and derivatives have been used as prognostic criteria in the course of the disease in various diseases. The prognostic nutritional index (PNI), the systemic immune-inflammation index (SII), the neutrophil-lymphocyte ratio (NLR) have been adapted as an indicator of inflammation and have been widely studied to define the severity of inflammation in some diseases. The aim of this study was to evaluate the relationship between parameters such as NLR, SII, PNI, controlling nutritional status (CONUT) score, nutritional risk index (NRI) and with immunonutrition status and disease activity in patients with ischemic stroke of small vessel, large vessel and other etiologies. Methods: We retrospectively evaluated the records of 1454 consecutive ischemic stroke patients hospitalized in the emergency department of Gaziosmanpasa Education and Research Hospital from 2019 to 2023. Results: Of the 1350 SVO patients included in the study, 58.8% had small vessel, 29.3% had large vessel and 11.9% had other etiologies. There was a significant difference between the 3 etiology groups for PNI and CONUT. The median PNI was 47.03 (41.33-52.85) in the other etiology group, 35.29 (33.69-37.25) in the small vessel group, and 34.11 (30.23-36.87) in the large vessel group. The CONUT median was 5(5-6) in the small vessel group, 5(4-6) in the large vessel group and 4(4-4) in the other etiology group. In addition, CONUT and PNI were also found to be independent risk factors for death. A negative significant correlation was observed between PNI and NLR (r:-0.692), SII (r:-0.591), CONUT (r:-0.685). Significant correlations were observed between CONUT and NLR (r:0.402), SII (r:0.312). Conclusion: PNI and SII were significantly associated with disease activity. PNI, CONUT and NRI as a more accurate prognostic indicator of nutritional status in patients with ischemic stroke of small vessel, large vessel and other etiologies. NLR and SII may be important predictive markers in the course and prognosis of stroke.

In this study, we investigated the role of Giardia EVs in cellular communication and their potential as vaccine candidates. Our findings revealed that Giardia EVs activate pro-inflammatory signalling cascades, including SAPK/JNK and ERK1/ERK2, as well as the NF-kB pathway, resulting in IκB-α degradation and p65 translocation to the nucleus, in mouse macrophages. Moreover, Giardia EVs increased the expression of genes encoding pro-inflammatory molecules, such as Il1β, Il6, Il4, Ptgs2, Nos2, and Tnf. Interestingly, Giardia EVs enhanced the maturation status of human Mo-DCs and significantly increased T-cell proliferation with a Th1 profile. Immunization studies demonstrated that Giardia EVs elicited antigen-specific antibodies, with IgG subclasses indicating a balance Th1/ Th2 response. Mass spectrometry analysis identified EV proteins (22 KDa and 50 KDa) that bind to serum antibodies of immunized mice including elongation factor 1-alpha, Alpha-7.3 giardin, tubulin, and Variant Surface Proteins (VSP), known antigenic proteins in Giardia infections. Overall, our results indicated that Giardia EVs modulate innate immune cells in vitro, induce antibody-based immune response in vivo, and contain conserved immunogenic proteins. Consequently, Giardia EVs hold promise as a cell-free vaccine candidate for giardiasis.

Background: SARS-CoV-2 Omicron JN.1 has the highest number of amino acid mutations in its receptor binding domain (RBD) and has acquired a hallmark L455S mutation. The immune evasion capability of JN.1 is a subject of scientific investigation. The US CDC used RT-qPCR SGTF as the proxy indicator of JN.1 infections for evaluation of the effectiveness of updated monovalent XBB.1.5 COVID-19 vaccines against JN.1 and recommended that all persons aged ≥6 months should receive an updated COVID-19 vaccine dose. Objective: Recommend Sanger sequencing for diagnosis of JN.1 infections to generate the data based on which guidelines are made to direct vaccination policies. Methods: The RNA in nasopharyngeal swab specimens from patients with clinical respiratory infection was subjected to nested RT-PCR, targeting a 398-base segment of the N-gene and a 445-base segment of the RBD of SARS-CoV-2 for amplification. The DNA sequences were analyzed for amino acid mutations. Results: The N-gene sequence showed Q229K, usually associated with Omicron BA.2.86 (+JN.1). The RBD sequence showed 24 amino acid mutations, including the hallmark L455S mutation for JN.1 and the V483del for BA.2.86 lineage. Conclusions: The CDC should consider Sanger sequencing of the RBD to diagnose JN.1 infections for statistical analysis in making vaccination policies.

Most research on colostrum quality and colostrum management focuses on maternal IgG transfer to the newborn calf. However, in addition to being a source of antibodies, colostrum has other components that influence passive immune transfer, nutrition, gut maturation, and thermoregulation. In this review, the constituents in the bovine colostrum, as well as their variation, are explored and it is discussed the biological role of colostrum on the newborn calf. Protein is the nutrient in higher concentration and fat is the nutrient with the most variation. There is a pronounced amplitude in the total solids content of colostrum, but the average concentration does not vary much between studies (24.7%). Bovine colostrum major components can vary with several factors, such as the region, season, breed, dry period length, and nutritional aspects of the dam. Bioactive components, cells, and microbiome variability are less understood, besides IgG. Regardless, they play crucial distinct roles in the physiological development of the newborn. However, a multi-interactive effect between these components, cells, and microorganisms is more likely to occur. Recently researched components in colostrum like miRNA, nucleo(t)sides, the milk fat globule membrane, oligosaccharides, minor proteins, and the microbiome are examples of promising interest areas of study.

Immune checkpoint inhibitors (ICIs), including anti-programmed cell death 1 ligand 1 (PD-L1) antibodies, are significantly changing treatment strategies for human malignant diseases including oral cancer. Cancer cells usually escape from immune system and acquire proliferative capacity and invasive/metastatic potential. We have focused on the two immune checkpoints, PD-1/PD-L1 and CD47/SIRPα in the tumor microenvironment of oral squamous cell carcinoma (OSCC), and performed a retrospective analysis of the expression of seven immune-related factors (PD-L1, PD-1, CD4, CD8, CD47, CD56 and CD11c), and examined their correlation with clinicopathological status. As a result, there were no significant findings relating seven immune-related factors and several clinicopathological statuses. However, the immune-checkpoint related factors (PD-1, PD-L1, CD47) were highly expressed in non-keratinized epithelium-originated tumors when compared to those in keratinized epithelium-originated tumors. It is of interest that immunoediting via immune checkpoint-related factors was facilitated in non-keratinized sites. Several researchers reported that keratinization of oral mucosal epithelia affected the immune response, but our present finding is the first study to show a difference of the tumor immunity in the originating-epithelium of OSCC, keratinized or non-keratinized. Tumor immunity, an immune escape status of OSCC might be different in the originating-epithelium, keratinized or non-keratinized.

Background: Platelets are increasingly recognised for their multifaceted roles in inflammation beyond their traditional involvement in haemostasis. This review consolidates knowledge on platelets as critical players in inflammatory responses. Methods: This study did an extensive search of electronic databases and identified studies on platelets in inflammation, focusing on molecular mechanisms, cell interactions, and clinical implications, emphasising recent publications. Results: Platelets contribute to inflammation via surface receptors, release of mediators, and participation in neutrophil extracellular trap formation. They are implicated in diseases like atherosclerosis, rheumatoid arthritis, and sepsis, highlighting their interaction with immune cells as pivotal in the onset and resolution of inflammation. Conclusion: Platelets are central to regulating inflammation, offering new therapeutic targets for inflammatory diseases. Future research should explore specific molecular pathways of platelets in inflammation for therapeutic intervention.

Background: The Liver Imaging Reporting and Data System (LI-RADS) combines standardized terminology with a classification system for imaging findings in patients with HCC, therefore rendering diagnostic biopsy unnecessary in many cases. This retrospective study included 23 patients with a biopsy diagnosis of HCC, performed either before or after local interventional procedures, in order to evaluate the histopathologic changes induced by previous procedures and their potential influence on the response to immune therapy. Material and Methods: The study encompassed a cohort of patients diagnosed with Hepatocellular Carcinoma (HCC). Diagnosis was established through contrast-enhanced computer tomography or magnetic resonance imaging that identified LI-RADS-5 nodules in conjunction with historical liver disease and elevated alpha-fetoprotein (AFP) levels, or through histological examination confirming positivity for glypican3, heat shock protein70, and glutamine synthetase. The study detailed the liver disease etiology, LI-RADS scores, characteristics and dimensions of HCC nodules, serum AFP concentrations, Edmondson-Steiner grading, and the expression of programmed cell death ligand 1 (PD-L1) in the tumor cells. Results: Among the study's cohort of Hepatocellular Carcinoma (HCC) patients, a portion had not received any prior treatments, while the remainder experienced local HCC recurrence following trans-arterial chemoembolization or radiofrequency ablation. Observations indicated elevated alpha-fetoprotein (AFP) levels in those who had not undergone any previous interventions, showing statistical significance. The Edmondson-Steiner classification predominantly identified grade III differentiation across patients, irrespective of their treatment history. Furthermore, an increase in intra-tumoral programmed cell death ligand 1 (PD-L1) expression was noted in patients who had not been subjected to previous therapies. Conclusion: Liver biopsy offers valuable insights for patients with Hepatocellular Carcinoma (HCC), assisting in the tailoring of immune therapy strategies, particularly in cases of recurrence following prior local interventions.

This is a brief critique of the functions—particularly olfactory functions—specified for the “Chemosensory Protein” (CSPs) molecule family. On the basis of these proteins’ presence in the sensory antennal lymph of locusts, odor chemosensory ligand binding functions have been hypothesized. According to this hypothesis, the entire protein molecule superfamily is referred to as “CSPs”. However, new information and developments in the field of CSP molecular research, such as the expression of CSP genes in the gut, brain, fat body, wings, epidermis, and pheromone gland, as well as gene expression profiling from most early developmental stages—that is, CSP expression well in advance of the appearance of chemical sense nerve cells—strongly suggest that the protein molecule has other roles that are unrelated to chemosensing. Moreover, CSPs are found in bacterial microbial prokaryote organisms in addition to insects and all other arthropods. Thus, we examine the molecule’s name, definition, RNA editing, protein structure, lipid binding properties, DNA interaction, and evolutionary characteristics in brief before referring to this protein family as “Chemosensory Proteins”. As a means of renaming this protein family, this review article discusses the latest findings (“CSP” is attached to the tail of bigger intracellular proteins) and attempts to compel all the data. Because of its highly conserved molecular distinctive feature (four adjacent cysteines), we propose renaming “CSPs” as “4CSPs” (4 Cysteines Soluble Proteins) and use at least for abbreviations for distinctive animal proteins the common peptide 5-letter code, such as “Bommo-4CSPs”.

Predictive biomarkers for immune checkpoint inhibitors (ICI), such as PD-L1 expression (TPS), remain limited in clinical applications. Improved novel ICI predictive biomarkers are urgently needed. We evaluated a live single-cell functional liquid biopsy cytokine profiling platform to track immunotherapy treatment response and outcomes. Peripheral blood mononuclear cell samples of healthy donors and NSCLC patients undergoing ICI-based therapies were collected longitudinally pre-/post-treatment under IRB-approved protocols. Samples were enriched for CD4+ and CD8+ T-lymphocytes and analyzed on the IsoLight platform. The single T-cells were captured in microchambers on IsoCode chips for cytokines profiling. Functional polyfunctionality data from 55,775 single cells were analyzed using the IsoSpeak software, kappa coefficient, and Kaplan-Meier survival plots. We found a significant difference between responders and non-responders in CD8+ T-cells’ changes in overall polyfunctionality and polyfunctional strength index (ΔPSI). ΔPSI score in CD8+ T-cells performed better than PD-L1 TPS and, when combined with PD-L1 TPS, strongly correlated with early ICI treatment response with a kappa coefficient of 1.0 (p=0.003). High CD4+ T-cells ΔPSI predicted a strong trend of improved PFS (3.9-fold) and OS (3-fold). In conclusion, single peripheral T-cell polyfunctionality dynamics analysis is a promising liquid biopsy profiling platform as NSCLC ICI predictive biomarker regardless of oncogene-addiction status.

Trace amines are a separate, independent group of biogenic amines, close in structure to classical monoamine neurotransmitters such as dopamine, serotonin and norepinephrine. G protein-coupled Trace Amine-Associated Receptors (TAAR) are mostly investigated for their involvement in the pathogenesis of neuropsychiatric disorders, but expression of TAAR family receptors is observed also in various populations of cells of the immune system. The review is focused on the basic information on the interaction of trace amines and their receptors with cells of the general immune system of humans and other mammals, as well as on data on TAARs role in the function of individual populations of myeloid and lymphoid cells. With further research on the regulatory role of the trace amine system in the pathogenesis of the immune response and determination of the biological mechanisms for their action it would be possible to develop new methods for treating diseases related to immune system dysfunctions.

This article describes a novel topical composition constituted by gamma-amino butyric acid (GABA) and microbial chondroitin sulfate. This composition, formulated by the author and manufactured in a certified facility in the United States of America, exhibits potential for non-invasive intervention in anxiety management, sleep quality enhancement, and promotion of brain-related functions like meditation and nonlocal consciousness. The core component comprises GABA, a key inhibitory neurotransmitter within the central nervous system, complexed with a suitable carrier molecule, microbial chondroitin sulfate. This complexation aims to enhance transdermal absorption and optimize delivery of GABA to target tissues. The proposed mechanism of action involves modulation of GABAergic signal transduction pathways. Application of the topical composition allows GABA penetration into the skin and potentially deeper tissues, where it interacts with GABA receptors. This interaction leads to mental calmness and relaxation as assessed by electroencephalography. The influence of GABAergic signaling on brain circuits demonstrated in this article, when associated with meditation and nonlocal consciousness, suggests potential for the composition to support these practices. The advantage of such an approach consists in avoiding the potential systemic side effects associated with oral or injectable administration of GABA, anxiolytics or hypnotics. Furthermore, the combination of GABA and microbial chondroitin sulfate may offer synergistic benefits, potentially enhancing the overall biological effects. In conclusion, this article presents a novel topical approach for managing anxiety, enhancing sleep quality, and potentially facilitating meditation and nonlocal consciousness through modulation of GABAergic signaling pathways. While further research is necessary, the potential for a non-invasive and potentially side-effect-free intervention in these areas is promising.

Coccomyxa subellipsoidea KJ (C-KJ) is a green alga with unique immunoregulatory characteristics. Here, we investigated the mechanism underlying the modification of T cell function by C-KJ components. The water-soluble extract of C-KJ was fractionated into protein (P) and sugar (S) fractions [acidic (AS), basic (BS), and neutral (NS)]. These fractions were used for the treatment of peripheral blood mononuclear cells stimulated with toxic shock syndrome toxin-1. Transcriptome analysis revealed that both P and AS enhanced the expression of the genes encoding metallothionein (MT) family proteins, inflammatory factors, and T helper (Th) 17 cytokine and suppressed that of those encoding Th2 cytokines in stimulated T cells. The kinetics of MT1 and MT2A gene expression showed a transient increase in MT1 and maintenance of MT2A mRNA after T cell stimulation in the presence of AS. The kinetics of Th17-related cytokine secretion in the early period were comparable to those of MT2A mRNA. Furthermore, our findings revealed that static, a STAT-3 inhibitor, significantly suppressed MT2A gene expression. These findings suggest that the expression of MTs is involved in the immune regulatory function of C-KJ components, which is partially regulated by Th17 responses, and may help develop innovative immunoregulatory drugs or functional foods.

Handedness reflects functional body and hemispheric lateralization, proving relevant to contextualize cognitive and behavioral profiles. This study aimed to determine the lateralization of the hands, feet and eyes in patients with various neurological disorders and to test the Edinburgh Handedness Inventory (EHI), a widely used handedness measure. The study design included a literature overview and a clinical study. The overview spanned the literature of the past 50 years since the EHI was developed. Three hundred seventy-four patients with immune-mediated (IM) or noIM neurological diseases and healthy subjects underwent personal and family history of handedness, stressful events and IM diseases, and EHI. The literature overview showed that handedness, which develops under the influence of genetic and acquired factors, is an indirect indicator of hemispheric lateralization; hemispheric lateralization is bidirectionally related to the immune system. In the clinical study, the EHI showed appropriate reliability and structural validity; its scores related to chronological age, onset age, and disease duration and helped distinguish patients with IM disease from other patients and healthy subjects. Therefore, handedness may change over the course of life under the influence of pathology and could predict IM neurological diseases. The EHI is an appropriate measure of handedness.

Aquaculture is rapidly becoming one of the pivotal sectors in the farm economy, driven by the increasing demand for high-quality animal protein at an affordable cost, especially with the escalating human population. However, the expansion of high-density fish populations also brings forth a challenge – the rapid transmission and spread of infectious disease agents among them. To combat this, vaccination is emerging as a reliable and standardized method for providing immunity against viral and bacterial outbreaks. The ideal vaccine is expected to be safe, effective, economical, and easily administered. The fish vaccination industry continually publishes new information on fish immunology and vaccinology, contributing to the improvement of vaccine formulation and efficacy. This review aims to offer insights into the current status of bacterial, viral, and parasitic diseases, discuss existing vaccinations, and address potential industry-threatening diseases like infectious edwardsiellosis, motile aeromonas septicemia, TiLV, salmon anemia, vibriosis, and white spot disease. Technological advancements have played a crucial role in enhancing our understanding of fish immunological mechanisms, leading to improved vaccine administration and the development of recombinant live attenuated, subunit, DNA, and RNA vaccines. However, challenges such as oral tolerance, vaccine degradation, and stressful environments persist, impacting vaccine efficacy. Addressing these challenges and gaining a deeper understanding of the fish immune system and host-pathogen interactions will be pivotal for future improvements, contributing to the sustainability of aquaculture and enhancing global food security.

Hashimoto's thyroiditis (HT) is essentially featured by self-tissue destruction by means of the adaptive immune responses that evade immune regulation. Vitamin D carries out an immunomodulatory role that appears to promote immune tolerance. The aim of this study is to elaborate a narrative review about the relationship between vitamin D status and HT and the role of vitamin D supplementation to reduce HT risk by modulating the immune system. There is an extensive literature confirming that vitamin D levels are significantly lower in HT patients compared to healthy people. On the other hand, after the supplementation with cholecalciferol in patients with HT and vitamin D deficiency, thyroid autoantibody titer decreased significantly, However, there are no conclusive results on the effect of vitamin D supplementation on the thyroid function. The confirmation of the beneficial effects of vitamin D in the prevention and treatment of autoimmune thyroid diseases require additional randomized, double-blind, placebo-controlled trials with longer follow-up.

Recently, immunotherapy has arisen as a novel treatment approach for patients with colorectal cancer (CRC), but the effectiveness of immunotherapy varies in these patients. We hypothesized that immune checkpoint molecules (ICMs), which are the targets of immunotherapy, are often exhibit concomitantly. Our objective was to investigate the patterns of ICM expression in patients with CRC and the differences in ICM expression based on the microsatellite instability status. Immunohistochemical expression of programmed cell death protein 1 (PD-1), programmed cell death ligand 1 (PD-L1), T cell immunoglobulin and mucin-domain containing-3 (TIM-3), and lymphocyte-activation gene 3 (LAG-3) in the tumor center and periphery was assessed in patients with non-metastatic colorectal cancer. We enrolled 83 patients with CRC: 40 with microsatellite stable (MSS) and 43 with microsatellite instability-high (MSI-H). PD-L1 was more frequently expressed in the tumor center in patients with MSI-H than that in patients with MSS (18 [41.9 %] vs. 3 [7.5 %], respectively; P < 0.001), and the same trend was observed for TIM-3 expression (30 [69.8 %] vs. 19 [47.5 %], respectively; P = 0.047). Concomitant expression of two or more ICMs was more frequently observed than no expression or expression of a single molecule in both MSS and MSI-H groups; 34 (79.7 %) patients with MSI-H and 23 (57.5 %) with MSS showed ICM expression at the tumor center, whereas 34 (79.7 %) patients with MSI-H and 22 (55 %) with MSS showed expression at the tumor periphery. Patients with the genetic characteristics of MSI-H showed higher expression levels of ICMs than that in patients with MSS, and predominantly, two or more ICMs were concurrently expressed. Our findings highlight the potential efficacy of the dual-blockade approach in immunotherapy, particularly in patients with MSI-H CRC.

In February 2004, the Food and Drug Administration (FDA) was the first to approve the combination of cisplatin (CDDP) and pemetrexed (PEM) as standard first-line chemotherapy for untreated, unresectable malignant pleural mesothelioma (MPM). However, after that approval, no progress was made in the standard first-line treatment of MPM for almost 15 years. Positive results from a phase 3 study (Mesothelioma Avastin Cisplatin Pemetrexed Study: MAPS) verifying the effect of bevacizumab, an anti-angiogenesis agent added to CDDP/PEM for unresectable MPM, were published in The Lancet in December 2015; however, this did not lead to approval by national drug regulatory agencies. Furthermore, no second-line treatment was established for cases refractory to CDDP/PEM. In August 2018, the Pharmaceuticals and Medical Devices Agency of Japan was the first in the world to approve monotherapy with nivolumab, an immune checkpoint inhibitor (ICI), for previously unresectable, advanced, or recurrent MPM. Following Japan, in October 2020, the FDA approved the combination of nivolumab and ipilimumab for the treatment of previously untreated, unresectable MPM. In this article, we review the transition of drug treatment for MPM, in light of the historical background, focusing on the benefits of ICIs.

Immune checkpoint inhibitors (ICI’s) are in the forefront of advanced Non Small Cell Lung Cancer (NSCLC) treatment. Still, only 27- 46% of patients respond to initial therapy with ICI’s and of those, up to 65% develop resistance within four years. After disease progression (PD), treatment options are limited, with 10% Objective Response Rate (ORR) to second or third-line chemotherapy. In this context, ICI rechallenge is an appealing option for NSCLC. Most data on the efficacy of ICI rechallenge are based on retrospective real-world studies of small, heavily pretreated, and heterogeneous patient groups. Despite these limitations, these studies suggest that ICI monotherapy rechallenge in unselected NSCLC patient populations who discontinued initial ICI due to PD is generally ineffective, with a median Progression-Free Survival (PFS) of 1.6-3.1 months and a Disease Control Rate (DCR) of 21.4%-41.6%. However, there is a subpopulation that benefits from this strategy, and further characterization of this subgroup is essential. Furthermore, immunotherapy rechallenge in patients who discontinued initial immunotherapy following treatment protocol completion and progressed after an immunotherapy-free interval showed promising efficacy, with a DCR of 75-81%, according to post-hoc analyses of several clinical trials. Future research of ICI rechallenge for NSCLC should focus on better patient stratification, to reflect the underlying biology of immunotherapy resistance more accurately.

In order for the body to function properly, it needs not only food, but also nutrients and non-nutritive bioactive compounds that have an immunomodulating effect. This applies not only to healthy people, but especially to people with accompanying chronic diseases, including type 2 diabetes. Unfortunately, the current food industry and the use of highly processed food promote nutritional deficiencies. Many studies confirm their occurrence in patients with type 2 diabetes. The article presents the influence of selected nutrients on the functioning of the immune system, which ensures homeostasis of the body, with particular emphasis on type 2 diabetes. The role of macroelements, microelements, vitamins and selected substances, such as omega-3 acids, coenzyme Q10 and alpha-lipoic acid. The minimum scope of tests that should be performed in patients to directly or indirectly determine the degree of malnutrition in this group of patients is presented.

Opossums, native to the Americas, are unique marsupials with over 100 species. The Common Opossum and Virginia Opossum are notable species. They are nocturnal, omnivorous, and adapt to various habitats. Their reproduction involves a short gestation and marsupial pouch development. Despite their ecological benefits like seed dispersal and insect control, their proximity to human habitats exposes them to pathogens, posing public health risks. These include protozoa, helminths, and arthropods that can spread zoonotic parasites and vector-borne diseases. The marsupial immune system, including opossums, is complex, rivaling eutherian mammals. Key immune genes were identified in the grey short-tailed opossum genome. CD1 protein and VpreB surrogate light chain were also found. Marsupials are proposed as ideal models for studying developmental immunology. A West Indian opossum (Didelphis marsupialis) was found and examined. Blood tests revealed abnormalities, including a low white blood cell count and signs of anemia. The results contribute to understanding the species’ health and adaptability in the wild.

Background This study aimed to determine the association between immune checkpoint inhibitors (ICIs) and the risk of herpes zoster (HZ) incidence in patients with lung cancer. Method We obtained national claims data of 51,021 patients from South Korea with lung cancer between August 2017 and December 2021. The study population was classified into ICIs and non-ICIs groups based on prescription of ICIs at least once during the study period. To estimate the effects of ICIs treatment compared with those without ICIs treatment on HZ incidence, we used the Cox proportional hazards model adjusted for sex, age, comorbidities, and concomitant use of immunosuppressive drugs. Stratified analyses based on sex, age, and comorbidities were conducted to identify corresponding risk factors. Results Of the 51,021 study participants, 897 (1.8%) were prescribed ICIs, and 2,262 (4.4%) were diagnosed with HZ. Approximately 75.6% of the patients were male, and the prevalence of diabetes, cardiovascular disease, and chronic lung disease in the ICIs group was significantly lower than that in the non-ICIs group. The Kaplan–Meier plot showed that the probability of incidence of HZ in the ICIs group was lower than that in the non-ICIs group. Additionally, treatment with ICIs was associated with a 31% lower risk of developing HZ when compared to that seen without ICIs treatment (95% confidence interval [CI], 0.48–1.00). This association was stronger in females (hazard ratio [HR], 0.42; 95% CI, 0.19–0.94) and those less than 68 years of age (HR, 0.58; 95% CI, 0.34–0.99). Conclusion In these real-world data from an Asian population with lung cancer, ICIs treatment might be associated with a reduced risk of HZ compared to that without ICIs treatment.

Intratumoral immune cytolytic activity (CYT), measured as the geometric mean of the expression of Granzyme-A (GZMA) and Perforin-1 (PRF1), has emerged as a critical factor in cancer immunotherapy, with significant implications for patient prognosis and treatment outcomes. Here, we review how different immune checkpoint pathways, the composition of Tumor Microenvironment (TME), antigen presentation and metabolic pathways, all regulate CYT. We also discuss the various methods through which CYT can be assessed. The detection and analysis of tumor-infiltrating lymphocytes using flow cytometry or immunohistochemistry provide important information on the immune cell populations within the TME. Gene expression profiling and spatial analysis techniques, such as multiplex immunofluorescence and imaging mass cytometry, allow researchers to study CYT in the context of the TME. We further report the significant clinical implications that CYT has, as its increased levels are associated with positive clinical outcomes and a favorable prognosis. Moreover, CYT can be used as a prognostic biomarker and aid in patient stratification. Measuring CYT through different methods offers promising paths for improving treatment responses. Overall, we highlight that the understanding and modulation of CYT levels is critical for improving cancer immunotherapy. Research into CYT and the factors that influence it has the potential to transform cancer treatment and improve patient outcomes.

Avian Influenza viruses (AIVs) has posed a significant pandemic threat since their discovery. This review mainly focuses on the epidemiology, virology, and pathogenesis, and treatments of avian influenza viruses. We delve into the global spread, past pandemics, clinical symptoms, severity, and immune response related to AIVs. The review also discusses various control measures, including antiviral drugs, vaccines, and potential future directions in influenza treatment and prevention. Lastly, by summarizing the insights from the previous pandemic control, this review aims to direct effective strategies for managing future influenza pandemics.

Gut microbiota composition can affect tumor microenvironment and its interaction with the immune system, thereby having implications on treatment predictions. This article reviews the studies available to better understand how gut microbiomes help the immune system to fight cancer. To describe this fact, different mechanisms, and approaches of utilizing probiotics to improve advancements in cancer treatment will be discussed. Moreover, not only the calorie intake but also the variety and quality of diet can influence cancer patient’s immunotherapy treatment because dietary patterns could impair the immunological activities either by stimulating or suppressing the innate and adaptive immunity. Therefore, it is interesting and critical to understand the gut microbiome composition as a biomarker to decide cancer immunotherapy outcomes and responses. Here, more emphasis would be given to the recent development in immunotherapies utilizing microbiota to improve cancer therapies which is beneficial for cancer patients.

Host immunological pathways have been proposed including TH1, TH2, TH3, TH9, TH17, TH22, TH1-like, and THαβ immune reactions. Besides TH2 and TH9 immune responses which are against multicellular parasites, host immunological pathways against viruses, intracellular micro-organisms (bacteria, protozoa, and fungi), and extracellular micro-organisms can use programmed cell death pathways to trigger immune reactions or to execute effective strategies to eliminate these pathogens. These programmed cell deaths include apoptosis, autophagic death, pyroptosis, ferroptosis, necroptosis, and NETosis. Apoptosis is related to host anti-virus eradicable THαβ immunity. Autophagic death is related to host anti-virus tolerable TH3 immunity. Pyroptosis is related to host anti-intracellular micro-organism eradicable TH1 immunity. Ferroptosis is related to host anti-intracellular micro-organism tolerable TH1-like immunity. Necroptosis is related to host anti-extracellular micro-organism eradicable TH22 immunity. NETosis is related to host anti-extracellular micro-organism tolerable TH17 immunity.

The DNA damage response (DDR) system is a complicated network of signaling pathways that detects and repairs DNA damage or induces apoptosis. Critical regulators of the DDR network include the DNA damage kinases ataxia telangiectasia mutated Rad3-related kinase (ATR) and ataxia-telangiectasia mutated (ATM). The ATR pathway coordinates processes such as replication stress response, stabilization of replication forks, cell cycle arrest, and DNA repair. ATR inhibition disrupts these functions, causing reduction of DNA repair, accumulation of DNA damage, replication fork collapse, inappropriate mitotic entry and mitotic catastrophe. Recent data have shown that the inhibition of ATR can lead to synthetic lethality in ATM-deficient malignancies. In addition, ATR inhibition plays a significant role in the activation of the immune system by increasing the tumor mutational burden and neoantigen load as well as by triggering the accumulation of cytosolic DNA and subsequently inducing the cGAS-STING pathway and the type I IFN response. Taken together, we review stimulating data showing that ATR kinase inhibition can alter the DDR network, the immune system and their interplay and therefore potentially provide a novel strategy to improve the efficacy of antitumor therapy, using ATR inhibitors as monotherapy or in combination with genotoxic drugs and/or immunomodulators.

SARS-CoV-2 virulence is known to increase with lowering of environmental temperature and solar ultraviolet radiation; therefore, we have focused our real-world nationwide study concerning with COVID-19 trends and dynamics on the coldest seasons of the year in Italy, the Western country hardest hit at the onset of the pandemic, comparing the autumn-winter of 2020 (before mass vaccination but when the emergency machinery was fully operative in terms of tracing and swabs) with the autumn-winter of 2021 (after mass vaccination), and analyzing the mortality burden by age groups and life stages in the years 2019 (pre-COVID-19), 2020 (before mass vaccination) and 2021 (after mass vaccination). Methods: During the state of national health emergency, the Civil Defense Department released the aggregate data coming from the Higher Institute of Health, the Ministry of Health, the Italian Regions, and the Independent Provinces, to inform the population (58.85 million people) about the pandemic situation, daily. Among these data there were the number of contagions, performed swabs, hospitalizations in Intensive Care Units (ICU), non-ICU patients, and deaths. By means of a team effort, we have collected and elaborated all these data, comparing the COVID-19 pandemic in Italy during the autumn-winter of 2020 with the autumn-winter of 2021. Moreover, we have extracted from the database of the National Institute of Statistics the total number of annual deaths in Italy during the years 2019, 2020 and 2021, comparing them to each other in order to evaluate the mortality burden attributable to COVID-19. Results: From the autumn-winter of 2020 to the autumn-winter of 2021, the contagions increased by ≈285%, however against a ≈290% increase in the performed swabs; therefore, the mean positivity rate passed from 8.74% before mass vaccination to 8.59% after mass vaccination. The unprecedent vaccination campaign allowed a ≈251% abatement in COVID-19 deaths, and a reduction of ≈224% and ≈228% in daily ICU and non-ICU hospitalizations due to COVID-19, respectively. Regarding COVID-19 deaths, in 2020 there was a mortality excess of ≈14.3% quantifiable in 105,900 more deaths compared to 2019, the pre-COVID-19 year; 103,183 out of 105,900 deaths occurred in older adults (≥60 years), which is equivalent to ≈97.4%, while in adults over 50, the segment of population just below older adults, in 2020 there were 2807 more deaths than in 2019. Surprisingly, from the analysis of our data, it is emerged that under the age of 40 in the years 2019, 2020 and 2021 there were 7103, 6808 and 7165 deaths, respectively. This means that in subjects under 40 during 2020 there were 295 fewer deaths than in 2019, while during 2021 there were 357 more deaths than in 2020, equivalent to ≈5.2% more. Conclusions: COVID-19 is a potential life-threatening disease mainly in older adults, as they are the most vulnerable due to inherent immunosenescence and inflammaging. Extensive vaccination in this segment of population with up-to-date vaccines is the means to reduce deaths, hospitalizations, and ICU pressure in the public interest. In the event of future threats, a new mass vaccination campaign must not be implemented without taking into account the individual age; it should primarily be aimed at people over 60 and at patients of any age with immune deficits, and secondly at people over 50. COVID-19 vaccination shows a favorable benefit-risk balance in older adults, while this balance falls under the age of 40; this younger segment of population should be therefore exempt from any mandatory vaccination.

Gliomas are central nervous system (CNS) derived tumors that originate from glial cells and affect six per 100,000 people in the United States. They are the most common form of CNS neoplasm and are highly diffusely infiltrative to surrounding brain tissue. Gliomas of diffusive nature are classified into different subcategories: astrocytomas, oligodendrogliomas, and ependymomas. Computed tomography (CT) and Magnetic Resonance Imaging (MRI) are used to determine tumor category and spread which may dictate treatment options. This paper focuses on emerging treatments of chemotherapy management with temozolomide and Avastin as well as emerging immune modulation treatment with vaccinations, manipulation of cellular checkpoints CTLA-4 and PD-1, co-receptor modulation of neuropilin-1, CAR-T cell therapy, and CRISPR-Cas9 gene editing. The employment of TMZ and BEV has been supported in the literature, however, more research is necessitated to fully optimize regimens and to avoid immune- and toxicity-related effects of these drugs. Moreover, an even closer consideration is warranted for current immunotherapies as they are in their infancy compared to TMZ and BEV. Thus, although promising emerging treatment options, therapies involving cancer vaccines, ICIs, immune modulation of neuropilin-1, CAR-T, and CRISPR-Cas9 technology require further investigation into their long-term efficacy and utility in treating gliomas.

Autism spectrum disorder (ASD) is a neuropsychiatric condition characterized by impaired social interactions and repetitive stereotyped behaviors. Growing evidence highlights an important role of the gut-brain-microbiome axis in the pathogenesis of ASD. Research indicates an abnormal composition of the gut microbiome and the potential involvement of bacterial molecules in neuroinflammation and brain development disruptions. Concurrently, attention is directed towards the role of short-chain fatty acids (SCFAs) and impaired intestinal tightness. This comprehensive review emphasizes the potential impact of maternal gut microbiota changes on the development of autism in children, especially considering maternal immune activation (MIA). The following paper evaluates the impact of the birth route on the colonization of the child with bacteria in the first weeks of life. Furthermore, it explores the role of pro-inflammatory cytokines, such as IL-6 and IL-17a and mother’s obesity as potentially environmental factors of ASD. The purpose of the present analysis is to advance our understanding of ASD pathogenesis, while also searching for the positive implications of the latest therapies, such as probiotics, prebiotics or fecal microbiota transplantation, targeting the gut microbiota and reducing inflammation. This review aims to provide valuable insights that could instruct future studies and treatments for individuals affected by ASD.

Chronic lymphocytic leukemia (CLL) is characterized by dysfunctional B cells. Immune checkpoint molecules such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), and programmed death-1 (PD-1) are upregulated in patients with CLL and may correlate with prognostic markers such as beta-2 microglobulin (B2M). The aim of this study was to evaluate the levels of immune checkpoints on B-cell subsets and to further correlate them with B2M levels in patients with CLL. We recruited 21 patients with CLL and 12 controls. B cell subsets and the levels of immune checkpoint expression were determined using conventional multi-color flowcytometry. Basal levels of B2M in patients with CLL were measured using an Enzyme-linked immunosorbent assay. Patients with CLL had increased levels of activated B cells when compared to the control group, p< 0.001. The expression of PD-1 and CTLA-4 were increased on activated B cells and memory B cells, p< 0.05. There were no associations between B2M levels and the measured immune checkpoints on B cell subsets, after adjusting for sex and age. African patients with CLL express elevated levels of PD-1 and CTLA-4 immune checkpoints on activated and memory B cell subsets. However, there is no correlation between these immune checkpoint expressions and B2M levels.

In this experiment, the fermented pineapple residue (FPR) was replaced with 0% (CON), 25% (T25) and 50% (T50) in the diet based on silage royal grass roxb for 30 days in the fattened fatten bulls to evaluate the effect of FPR on growth performance, serum indicators and rumen characteristics.Thirty Simmental calves were selected and divided into three groups according to a completely random design.The temperature and humidity of the cowshed shall be measured every day.Rectal temperature and blood of cattle were measured, and blood and immune markers were measured.The results showed that the rectal temperature decreased significantly when adding 25% fermented pineapple residue (P&lt;0.05), and the rectal temperature decreased significantly when adding 50% fermented pineapple residue (P&lt;0.01).The content of T4 and TC in serum of cattle in T50 group was significantly lower than that in the control group (P&lt;0.01), and the content of T3 was significantly higher than that in the control group (P&lt;0.05), and the content of CR was significantly lower than that in the control group (P&lt;0.01). Fermented pineapple residue can indeed improve the oxidative (heat) stress resistance of finishing cattle. In the correlation experiment, bacterial genera such as Succinniclassicum, Melainabacteria, Lachnospiraceae, and Fibrobacteres all showed significant or extremely significant correlations with heat stress-related indicators.

Porcine epidemic diarrhea virus (PEDV) has affected the pork industry worldwide and during outbreaks the mortality of piglets has reached 100%. Lipid nanocarriers are commonly used in the development of immunostimulatory particles due to their biocompatibility and slow-release delivery properties. In this study, we developed a lipid nanoparticle (LNP) complex based on glycyrrhizinic acid (GA) and tested its efficacy as an adjuvant in mice immunized with the recombinant N-terminal domain (NTD) of porcine epidemic diarrhea virus (PEDV) spike (S) protein (rNTD-S). The dispersion stability analysis (Z-potential–27.6 mV) confirmed the size and charge stability of the LNP-GA, demonstrating that the particles were homogeneously dispersed and strongly anionic, that favors nanoparticles binding with the rNTD-S protein, which showed a slightly positive charge (2.11 mV) by in silico analysis. TEM image of LNP-GA revealed nanostructures with a spherical-bilayer lipid vesicle (⁓100 nm). The immunogenicity of the LNP-GA-rNTD-S complex induced an efficient humoral response 14 days after the first immunization (P &lt; 0.05) as well as an influence on the cellular immune response by decreasing serum TNF-α and IL-1β concentrations, which was associated with an anti-inflammatory effect.

Dengue virus (DENV) is spread by Aedes aegypti and causes significant global health risks. Alternative techniques are urgently needed because the current control mech-anisms are insufficient to reduce the transmission of DENV. Introducing Wolbachia pipientis into Ae. aegypti inhibits DENV transmission, however, the underlying mechanisms are still poorly understood. Innate immune effector upregulation, the regulation of autophagy, and intracellular competition between Wolbachia and DENV for lipids are among the theories for the mechanism of inhibition. Further-more, mainly three immune pathways Toll, IMD and JAK/STAT are involved in the host for the suppression of the virus. These pathways are activated by Wolbachia and DENV in the host and are responsible for the upregulation and downregulation of many genes in mosquitoes, which ultimately reduces the titer of the DENV in the host. The functioning of these immune pathways depends upon the Wolbachia, host and virus interaction. Here, we summarize the current understanding of DENV recognition by the Ae. aegypti’s immune system, aiming to create a comprehensive picture of our knowledge. Additionally, we investigated how Wolbachia regulates ac-tivation of multiple genes associated with the Toll and IMD pathway, for the reduc-tion of arboviruses.

The emergence of SARS-CoV-2 subvariant BA.2.86, also known as Pirola, has raised concerns about its transmissibility, virulence, and immune escape. The aim of this letter is to address the current evidence on the origin, spread, and characteristics of Pirola, and discuss its implications for public health and vaccine development. The need for enhanced surveillance, genomic sequencing, and epidemiological studies to monitor the evolution and impact of Pirola and other SARS-CoV-2 variants are highlighted in this letter along with the importance of global cooperation and coordination to prevent and control future outbreaks of this novel coronavirus strain.

Inflammation is widely acknowledged as a significant characteristic of cancer, playing a substantial function in both the initiation and advancement of cancers. In this research, we planned to investigate the comparison among pan-immune inflammation markers and other well-known markers (systemic immune inflammation index and neutrophil to lymphocyte ratio) to predict prognosis in individuals treated with radical cystectomy for bladder cancer. Methods: In this retrospective analysis, we focused on preoperative PIV, systemic immune inflammation index (SII), and neutrophil-lymphocyte ratio (NLR) in 193 individuals managed with radical cystectomy for bladder cancer between January 2016 and November 2022. Multivariable logistic regression assessments were perfomred to assess the predictive capabilities of PIV, SII, and NLR for infiltration of lymph nodes (N), aggressive tumor stage (pT3/pT4), and any non-organ limited disease at the time of RC. Multivariable Cox regression analyses were conducted to assess the predictive impact of PIV on Relapse-free survival (RFS), Cancer-specific survival (CSS), and Overall survival (OS). Results: Our individuals were divided into high PIV and low PIV cohorts using the optimal cut-off value (340.96 x 109/ L) based on receiver operating characteristic curve analysis for relapse-free survival. In multivariable preoperative logistic regression models, only SII and PIV correlated with the infiltration of lymph nodes, aggressive disease, and any non-organ confined disease. In multivariable Cox regression models considering presurgical clinicopathological variables, an higher PIV was associated with diminished RFS (p = 0.017) and OS (p = 0.029). In addition, in multivariable Cox regression models for postoperative outcomes, a high PIV correlated with both RFS ( p = 0.034) and OS ( p= 0.048). Conclusions: Our study suggests that PIV and SII are two very similar markers that may serve as an independent and significant predictor of aggressive disease and worse survival impacts on individuals undergoing radical cystectomy for bladder neoplasm.

Coronaviruses are a large family of diverse enveloped RNA viruses found in numerous animal species. They are well-known for their ability to cross species barriers and have been transmitted from bats or intermediate hosts to humans on several occasions. Four of the seven human coronaviruses (hCoVs) are responsible for approximately 20% of common colds (hCoV-229E, -NL63, -OC43, -HKU1). Two others (SARS-CoV-1 and MERS-CoV) cause severe and frequently lethal respiratory syndromes but have only spread to very limited extents in human populations. In contrast, SARS-CoV-2, while exhibiting intermediate pathogenicity, has a profound impact on public health due to its enormous spread. In this review, we discuss which initial features of the SARS-CoV-2 Spike protein and subsequent adaptations to the new human host may have helped this pathogen to cause the COVID-19 pandemic. Our focus is on host forces driving changes in the Spike protein and their consequences for virus infectivity, pathogenicity, immune evasion and resistance to preventive or therapeutic agents. In addition, we discuss the significance and perspectives of broad-spectrum therapeutics and vaccines.

Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder. Diagnosis can take a long time, especially in the presence of confounding factors, and it is, at least in part, of exclusion. AOSD is generally mild, however a small percentage of patients can develop a fearsome as well potentially fatal complication, the macrophage activation syndrome (MAS), which is also referred to as hemophagocytic lymphohistocytosis (HLH). This condition is correlated with a cytokine storm production and monocyte/macrophage overactivation, and typically occurs with rash, pyrexia, pancytopenia, hepatosplenomegaly and systemic involvement. Exitus occurs in approximately 10% of cases. The Histiocyte Society, which is a nonprofit organization committed to improving the lives of patients with histiocytic disorders, currently suggests etoposide in combination with dexamethasone for the treatment of HLH/MAS, although a multidisciplinary collaboration using the resources and expertise of several specialists (e.g. rheumatologist, infectiologist, critical care medicine specialist) is always recommended. Hereby we propose the detailed description of the clinical case of a previously healthy young woman in which MAS was the dramatic onset manifestation of AOSD and whose diagnosis posed a real clinical challenge.

Introduction: Flow-cytometry (FC) is a powerful tool that can assist in lymphoma diagnosis in lymph node (LN) specimens. Although lymphoma diagnosis and classification are mainly based on tumor cell characteristics, surrounding cells are less employed in this process.Methods: We retrospectively investigated alterations in the ploidy status, proliferative cell fraction (PF) and the percentages of surrounding immune cells in 62 consecutive LN specimens with B-Cell Non-Hodgkin Lymphoma (B-NHL) that were submitted for FC evaluation between 2019-2022.Results: Compared with indolent B-NHLs, aggressive B-NHLs show increased DNA aneuploidy and PF, increased monocytes, immature-granulocytes, mature granulocytes, CD8⁺ T-cells, Double-Negative-T-cells and Double-Positive-T-cells, and decreased total CD45⁺ cells, total lymphocytes, CD4⁺ T-cells and CD4/CD8 ratio. Receiver operating characteristic analysis determined PF > 6.8% and immature-granulocytes > 0.9% as optimal cutoffs with highest specificity and sensitivity in differentiating aggressive and indolent B-NHLs.Conclusions: These findings further strength the diagnostic value of DNA content analysis by FC and suggest the utilization of tumor surrounding immune cells in NHL diagnosis and classification.

Studies report variable effects of sex hormones on serious diseases. Severe disease and mortality rates in COVID-19 show marked gender differences that may be related to sex hormones. Sex hormones regulate the expression of the viral receptors ACE2 and TMPRSS2, which affect the extent of viral infection and consequently cause variable outcomes. In addition, sex hormones have complex regulatory mechanisms that affect the immune response to viruses. These hormones also affect metabolism through obesity, and severe disease can result from complications such as thrombosis. This review presents the latest research on the regulatory functions of hormones in viral receptors, immune responses, complications as well as their role in COVID-19 progression. It also discusses the therapeutical possibilities of these hormones by reviewing the recent findings of clinical and assay studies.

Keywords: Cell-free DNA, sepsis, oxidative stress, immunoredox modulation, cecal ligation and puncture, toll-like receptor

This is a brief critique of the functions—particularly olfactory functions—specified for the “Chemosensory Protein” (CSPs) molecule family. On the basis of these proteins’ presence in the sensory antennal lymph of locusts, odor chemosensory ligand binding functions have been hypothesized. According to this hypothesis, the entire protein molecule superfamily is referred to as “CSPs”. However, new information and developments in the field of CSP molecular research, such as the expression of CSP genes in the gut, brain, fat body, epidermis, and pheromone gland, as well as gene expression profiling from most early developmental stages—that is, CSP expression well in advance of the appearance of chemical sense nerve cells—strongly suggest that the protein molecule has other roles that are unrelated to chemosensing. Moreover, CSPs are found in bacterial microbial prokaryote organisms in addition to insects. Thus, we examine the molecule’s name, definition, RNA editing, protein structure, lipid binding properties, DNA interaction, and evolutionary characteristics in brief before referring to this protein family as “Chemosensory Proteins”. This article tries to compel and discuss the most recent information as a way to rename this protein family. Because of its highly conserved molecular distinctive feature (four adjacent cysteines), we propose renaming “CSPs” as “4CSPs” (4 Cysteines Soluble Proteins).

Proteins are considered to be the main carriers of antigenic properties of Mycobacterium tuberculosis and Mycobacterium bovis, the causative agents of tuberculosis, the most serious infectious disease. Neutrophils, following resident macrophages, are among the first to attack the mycobacteria in defense of the organism. Neutrophils themselves are also the target of mycobacterial products; and their effect on neutrophil functions has been less studied. We have obtained about 70 protein fractions from M. bovis lysate; among them four protein fractions (10, 22, 24, and 40 kDa) had high serological activity against the serum of a rabbit immunized with M. bovis cells. We studied the effect of the serologically active proteins isolated from M. bovis on the generation of reactive oxygen species by bone marrow granulocytes of the Balb/c mouse, evaluated by luminol-dependent chemiluminescence. For comparison, two synthetic peptides (both 3 kDa) carrying immunogenic epitopes of MPB 70 protein (M. bovis) were taken. Proteins of 10, 22, and 24 kDa at concentrations of 83, 80, and 59 ng/mL, respectively, were found to activate ROS generation by mouse granulocytes. The 10- and 40-kDa antigens inhibited the receptor-mediated respiratory responses to opsonized zymosan (OZ) and N-formyl-MLF peptide (fMLF) but significantly enhanced the response to the phorbol ester PMA, which directly activates protein kinase C. Antigens with molecular weights of 22 and 24 kDa enhanced the fMLF-induced response and had no effect on the response activated by PMA. The response to OZ was suppressed in the presence of the 22 kDa protein. Synthetic peptides over a wide range of concentrations showed no activity in any case. All M. bovis proteins examined did not affect both proliferation and cell viability of the A549 and THP-1 cells; therefore, they have no cytotoxic or proliferative effects. Thus, serologically active proteins with molecular weights of 10, 22, 24, and 40 kDa isolated from M. bovis modulated the respiratory responses of mouse granulocytes induced by the formyl peptide, while proteins of 10, 22, and 40 kDa inhibited the responses induced by OZ.

Immune-mediated necrotizing myopathy (IMNM) is a rare and severe disease that corresponds to a specific entity of idiopathic inflammatory myopathy. Patients with IMNM suffer from proximal muscle weakness, and present high levels of creatine kinase and necrotic myofibers. Anti-Signal Recognition Particle (SRP) and anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase autoantibodies (HMGCR) have recently been identified in two thirds of patients with IMNM and are used as a hallmark of the disease. In this review, we provide a detailed description of these antibodies and the tests used to detect them in the serum of patients. Based on in vitro studies and mouse models of IMNM, we will discuss the role of autoantibodies in the pathogenesis of the disease. Finally, in the light of the latest knowledge, we will conclude with a review of recent therapeutic approaches.

The crosstalk between gut microbiota, intestinal epithelial cells, and innate and adaptive immune system governs the maintenance of the intestinal homeostasis. Any interference in this tight dialogue and in the processes preserving cellular homeostasis (e.g., autophagy) may dysregulate the immune response and impair the clearance of harmful bacteria favoring the dysbiotic alteration of the microbic flora that leads to chronic inflammation. Gut dysbiosis is strongly associated with gastrointestinal inflammatory disorders, among them the inflammatory bowel disease (IBD). This review discusses the current knowledge on IBD, from the genetic background of high-risk patients to the molecular mechanisms underlying the disease, the contribution of the microbic flora, and the role of autophagy in intestinal epithelial cells and provides the state of art regarding the targeted-nutritional approaches aimed to restore the beneficial crosstalk between an “anti-inflammatory” microbiota and the host. Analysis of the molecular pathogenesis of IBD will help identify genetic and diet-associated risk factors and thus suggest personalized strategies to prevent and manage the disease to improve quality of life with long-term maintenance of the remission phase.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare but severe adverse event that was first observed during the global vaccination campaign against SARS-CoV-2 infection, specifically in those receiving adenoviral vector-based vaccines for Coronavirus disease 2019 (COVID-19). VITT develops 4 to 42 days post-vaccination and is characterized by the development of platelet-activating anti-platelet factor 4 (PF4) antibodies, leading to thrombocytopenia and thrombosis at unusual sites. The rise in awareness and subsequent prompt recognition of VITT was paramount in reducing mortality. Moreover, as vaccination campaigns around the world continue, a better understanding of VITT not only has important clinical implications but is also crucial for future vaccine development. In this review, we summarize the clinical features, pathophysiology, and incidence rates of VITT as well as highlight other anti-PF4 antibody-mediated disorders of growing clinical significance.

A wide variety of bioactive peptides have been identified in the central nervous system and several peripheral tissues in the ascidian Ciona intestinalis type A (Ciona robusta). However, hemocyte endocrine peptides have yet to be explored. Here, we report a novel 14-amino acid peptide, CiEMa, that is predominant in the granular hemocytes and unilocular refractile granulocytes of Ciona. RNA-seq and qRT-PCR revealed the high CiEma expression in the adult pharynx and stomach. Immunohistochemistry further revealed the highly concentrated CiEMa in the hemolymph of the pharynx and epithelial cells of the stomach, suggesting biological roles in the immune response. Notably, bacterial lipopolysaccharide stimulation of isolated hemocytes for 1-4 hours resulted in increased CiEMa secretion. Furthermore, CiEMa-stimulated pharynx exhibited mRNA upregulation of the growth factor (Fgf3/7/10/22), vanadium binding proteins (CiVanabin1 and CiVanabin3), and forkhead and homeobox transcription factors (Foxl2, Hox3, and Dbx), but not antimicrobial peptides (CrPap-a and CrMam-a) or immune-related genes (Tgfbtun3, Tnfa, and Il17-2). Collectively, these results suggest that CiEMa plays roles in signal transduction involving tissue development or repair in the immune response, rather than in the direct regulation of immune-response genes. The present study identified a novel Ciona hemocyte peptide, CiEMa, providing insights into the molecular and functional diversity of the immune response in chordates.

Although lymphoma is the most frequent malignancy in common variable immunodeficiency (CVID), solid tumors, especially under influence of oncogenic viruses, are not considered. Furthermore, in vitro genetic studies and cell cultures are not adequate for immune system and HBV interaction. We adopted previously introduced clinical model of host-virus interaction (i.e. infectious process in immunodeficiency) for analysis of B cells and specific IgG role (observational study of a CVID patient who received intravenous immunoglobulin (IVIG)) Suddenly, the patient deteriorated with positive result of HBs, HBV-DNA (369x106copies). In spite of lamivudine therapy and IVIG escalation (from 0.3 to 0.4g/kg), CT showed 11cm intrahepatic tumor (hepatocellular carcinoma). Anti-HBs had been positive in time-lapse analysis (range 111-220 IU/ml). Replacement therapy intensification was complicated by immune complex disease with renal failure. The fulminant HCC in CVID and the development of the tumor as the first sign is interesting. Unfortunately, treatment with hepatitis B immune globulins (HBIG) plays a major role in posttransplant maintenance therapy. Anti-HBs substitution has not been proven to be effective, oncoprotective nor safe. Therefore, immunosuppression in HBV-infected recipients should be carefully minimized, patient selection more precise with the exclusion of HBV-positive donors. Our clinical model show HCC pathway with important humoral host factors, contrary to epidemiological/cohort studies highlighting risk factors only (e.g. chronic hepatitis). Lack of cell cooperation, B cell deficiency observed in CVID plays a crucial role in high HBV replication, especially in carcinogenesis.

The pandemic SARS-CoV-2 continues to evolve to give rise to variants of concern that can escape vaccine-induced immunity. As such, more effective vaccines are urgently needed. In this study, we evaluated virus-like particle (VLP) as a vaccine platform for SAS-CoV-2. The spike, envelope, and membrane proteins of the SARS-CoV-2 Wuhan strain were expressed by a single recombinant baculovirus BacMam and assembled into VLPs in cell culture. The morphology and size of the SARS-CoV-2 VLP as shown by transmission electron microscopy was found to be similar to the authentic SARS-CoV-2 virus particle. In a mouse trial, two intramuscular immunizations of the VLP BacMam with no adjuvant elicited spike-specific binding antibodies in both sera and bronchoalveolar lavage fluids. Importantly, BacMam VLP -vaccinated mouse sera showed neutralization activity against SARS-CoV-2 spike pseudotyped lentivirus. Our results indicated that the SARS-CoV-2 VLP BacMam stimulated spike-specific immune responses with neutralization activity.

Sarcomas are a group of malignancies of mesenchymal origin with plethora of subtypes. Given the sheer heterogeneity of various subtypes and rarity of the disease, management of sarcomas has been challenging with poor patient outcomes. Surgery, radiation therapy and chemotherapy have remained the backbone of treatment in patients with sarcoma. The introduction of immunotherapy has rev-olutionized the treatment of various solid and hematological malignancies. In this review, we discuss basics of immunotherapy and immune microenvironment in sarcomas, various modalities of im-munotherapy such as immune checkpoint blockade, oncolytic viruses, cancer targeted antibodies, vaccine therapy and adoptive cell therapies like CAR T-cell therapy, T cell therapy, TCR therapy.

Alternaria alternata is a saprophyte and is also known to cause many opportunistic infections in humans. Alternaria infections are important factors of morbidity and mortality in im-mune-compromised and solid organ transplant (SOT). Sensitivity to the airborne fungus Alter-naria alternata is also believed to be a common cause of allergic asthma. Therapies are limited by the lack of knowledge about the role of individual fungal gene products and symptoms in im-mune-compromised and transplant patients. This review summarizes the published case studies on Alternaria alternata infections in transplant patients.

A single Cancer immunotherapy has ushered in a transformative era in oncology, bringing forth unprecedented promise and opportunities. However, even with its significant breakthroughs, the domain faces the continual issue of treatment resistance. Such resistance not only restricts the broad effectiveness of these pioneering treatments but also highlights the imperative need for further research. Delving into the complex world of cancer immunotherapy resistance, we identify a range of mechanisms, from primary and secondary resistance to the notable effects of genetic and epigenetic variables, and the pivotal importance of the tumor microenvironment (TME). Additionally, we emphasize the need for innovative strategies to mitigate this resistance, including combination treatments, customized immune checkpoints, and instantaneous monitoring. By advocating for these cutting-edge methods, we foresee a direction that incorporates personalized healthcare, enhanced treatment options, and a steadfast dedication to the welfare of patients. Through a comprehensive and diverse approach, we aim to address the hurdles posed by resistance, elevating cancer immunotherapy as a symbol of hope for patients worldwide.

. Cucurbiturils are a family of macrocyclic oligomers capable of forming host-guest complexes with various molecules. Due to noncovalent binding to drug molecules and low toxicity, cucurbiturils has been extensively investigated as a potential carrier for drug delivery. However, the immune system interactions with different drug carriers, including cucurbiturils, are still under investigation. In this study, we focused on cucurbiturils immunosafety and immunomodulation properties in vivo. We measured blood counts, lymphocyte subpopulations in blood, spleen, and bone marrow, and assessed in vivo toxicity to spleen and bone marrow cells after intraperitoneal administration to mice. We also evaluated the effect of cucurbiturils on cellular and humoral immune responses. Cucurbiturils in high concentrations effect on the immune system in vivo. The action of various cucurbiturils differs in different homologues, which, apparently, is associated with different interactions in the internal environment of the body.

Thirty-six healthy 21-day-old weaned ternary piglets (Duroc × Landrace × Yorkshire) were randomly divided into 2 treatments with 18 replicates per treatment and 1 pig per replicate. The control group was fed with basal diet and the test group was fed with diets supplemented with 1 kg/t tea residue. The test period was 28 days. The results are as follows: The addition of tea residue in the diet has no significant effect on the growth performance of weaned piglets (P > 0.05), but it could significantly reduce the diarrhea rate of piglets from 1 to 7 days and 1 to 28 days (P < 0.05). Compared with the control group, the dietary supplementation of tea residue had no significant effect on nutrient apparent digestibility, plasma biochemical indexes and plasma immune indexes (P > 0.05), but increased the content of glutathione in plasma (P < 0.05). Tea residue had no significant effect on the morphology of jejunum and ileum of piglets (P > 0.05), but it could significantly reduce the content of chloride ion in feces (P < 0.05). Compared with the basal diet group, there was no significant difference in the relative expression of TMEM16A and CFTR mRNA in the colon of weaned piglets (P > 0.05). The whole-cell patch clamp recording showed that the TMEM16A and CFTR ion channels could be activated by ionomycin and forskolin, respectively. However, when the HT-29 cells transfected with TMEM16A and CFTR channels were treated with tea residue extract, it could significantly inhibit the chloride current of the TMEM16A and CFTR ion channels (P < 0.05).

To investigate the effects of plant polysaccharides combined with boric acid on digestive function, immune function, and harmful gas and heavy metal contents in faeces of finishing pigs, for this study, 90 healthy three-way cross-bred pigs were selected and randomly divided into five groups: Con) A control, fed basic feed; BA) fed basic feed supplemented with 40 mg/kg of boric acid; BA+APS) fed basic feed supplemented with 40 mg/kg of boric acid and 400 mg/kg of Astragalus polysaccharides; BA+GLP) fed basic feed supplemented with 40 mg/kg of boric acid with 200 mg/kg of Ganoderma lucidum polysaccharides; and BA+EPS) fed basic feed supplemented with 40 mg/kg of boric acid and 500 mg/kg of Echinacea polysaccharides. Compared with the Con, the average daily gain (ADG) and trypsin activity were higher in BA, along with there being increased glutathione peroxidase (p < 0.05); furthermore, lower malondialdehyde content and harmful substance emissions from manure were observed (p < 0.05). Compared with BA, increases in ADG, gain-to-feed ratio (G/F), trypsin, and maltase activities were observed in BA+EPS (p < 0.05), as well as a lower NH3 emissions (p < 0.05). Compared with BA, BA+APS exhibited higher ADG, average daily feed intake (ADFI), G/F, trypsin, and maltase activities (p < 0.05), while H2S emissions were lower (p < 0.05). And Taken together, our findings reveal that supplementation with boric acid and plant polysaccharides in the diet of finishing pigs synergistically improved their growth performance, trypsin and maltase activities, and immune function, while also discovered the intestinal digestive enzymes, serum inflammatory factors, oxidative stress responseand emissions of harmful gases and heavy metals from feces and urine were tightly related, further reducing the impact of fecal pollution generated by modern animal husbandry on the environment.

Ulcerative colitis is a chronic immune-mediated disease of unclear etiology, affecting people of different ages and significantly reducing the quality of life. Modern methods of therapy are mainly represented by anti-inflammatory drugs and are not aimed at a specific pathogenetic factor. In this study, we investigated the effect of transplantation of sterile stool filtrate from healthy donors on the induction of anti-inflammatory immune mechanisms. It was shown that performing such a procedure in patients with ulcerative colitis caused the appearance of T helper cells in the blood, which reacted to the content of sterile stool filtrates in an antigen-specific manner and produced IL10. At the same time, cells of the same patients before therapy in response to the addition of sterile stool filtrates were less reactive and predominantly produced IL4, indicating its pro-inflammatory skewing. The obtained data demonstrated the effect of an anti-inflammatory shift in the T-helper response after transplantation of sterile stool filtrate, which increased and persisted for at least three months after the procedure.

This research is aimed to investigate the effects of Lactoplantibacillus plantarum (L. plantarum) on growth performance, oxidation resistance, immunity, as well as cecal microbiota in broilers. This work classed three hundred and sixty 1-day-old broilers as three groups randomly, including control (CON, basal diet), antibiotic (ANT, 75 mg kg-1 chlortetracycline added into basal diet), or probiotic group (LP, 5×108 CFU kg-1 Lactoplantibacillus plantarum HJLP-1 contained within basal diet). Animal were then fed for 42 days, and each group consisted of 15 broilers for 8 replicates. Compared with CON, L. plantarum supplementation significantly improved the average weight daily gain (AWDG) (P < 0.05) while reducing feed-to-gain ratio over the entire supplemental period (P < 0.05). Birds fed L. plantarum had marked lower serum ammonia and xanthine oxidase levels (P < 0.05) than those in ANT and CON. Significant improvements (P < 0.05) of superoxide dismutase, catalase, serum IgM and IgY contents in broilers fed L. plantarum were also observed when compared those in CON and ANT groups. Both L. plantarum and antibiotics decreased the pro-inflammatory factor IL-1β level significantly (P < 0.05), while only L. plantarum promoted the anti-inflammatory factor IL-10 level dramatically in the serum (P < 0.05) compared with CON. The L. plantarum dramatically (P < 0.05) increased acetic acid and butyric acid concentrations in the cecal contents，when compared to those in CON and ANT. Among the differences revealed by 16S rRNA analysis, L. plantarum markedly improved the community richness of cecal microbiota. At the genus level, butyric acid-producing bacteria Ruminococcus and Lachnospiraceae were found in higher relative abundance in samples of L. plantarum treated birds. In conclusion, dietary L. plantarum supplementation promoted the growth and health of broilers, likely by inducing a shift in broiler gut microbiota toward short-chain fatty acid (SCFA)-producing bacteria. Therefore, L. plantarum has tremendous potential as an alternative for antibiotics in poultry breeding.

Insect meal as a protein source has been considered a sustainable way to feed animals. H. illucens and T. molitor larvae meal are considered high protein sources for poultry, also presenting considerable amounts of fatty acids, vitamins, and minerals. However, other potential components in insect meal and insect oil have been more studied nowadays. Chitin, lauric acid, and antimicrobial peptides can present antimicrobial and prebiotic functions, indicating that low inclusions of insect meal can beneficially affect broilers` health and immune responses. This systematic review was developed to study the impact of insect products on health parameters of broilers, and a metanalysis was conducted to evaluate the effects on performance. A database was obtained based on a selection of manuscripts from 2016 to January 2023, following the mentioned parameters. There were positive effects of both H. illucens and T. molitor meal or oil products on poultry health status, especially in microbiota population, immune responses, and antimicrobial properties. The average daily gain was greater in broilers fed T. molitor meal compared to H. illucens meal (p = 0.002). The results suggest that low levels of insect meal were suitable for broilers, without result in negative effects on performance, while the insect oil can totally replace soybean oil without negative impacts.

(1) Background: We comprehensively evaluated the expression of therapeutically targetable immune checkpoint molecules on celiac disease. We have focused on the alteration of the CD200/CD200R pathway and Elafin expression in celiac disease and discussed their roles in regulating the immune response. There are limited data related to the expression or function of these molecules in celiac disease. This finding could significantly contribute to the understanding of the clinical manifestation of celiac disease; (2) Methods: CD200, CD200R and Elafin distribution was determined by ELISA and immunohistochemistry analyses in serum and biopsies of CD patients. Analyses of Th1 and Th17 cytokines were determined. PCR amplification of a fragment of the PI3 gene was carried out using genomic DNA isolated from whole blood samples of the study subjects. Different aliquots of the PCR reaction product were subjected to RFLP analysis for SNP genotyping and detection; (3) Results: We characterized the expression and function of the CD200–CD200R axis and PI3 in celiac disease. A significantly higher level of soluble CD200, CD200R and lower expression of PI3 in serum of CD patients was observed compared to healthy controls. Consistent with our results, CD200 expression is regulated by IFN-gamma. Interaction of CD200/CD200R leads to production of type Th1 and Th17 cytokines. Regarding the PI3 genotype, the CT genotype proportion SNP rs1733103 and the GG genotype SNP rs41282752, were predominant in CD patients. SNP rs1733103 showed a significant association between the SNP variables and CD; (4) Conclusions: In celiac disease the immune checkpoint is compromised or dysregulated, which can contribute to inflammation and the autoimmunity process. The study of these checkpoint points will led to the development of targeted therapies aimed at restoring immunological balance in CD. Specific coding regions of the PI3 gene splice variants predispose the Elafin protein, both at the transcriptional and post-translational levels, to modify its expression and function, resulting in reduced differential functional protein levels in patients with active celiac disease.

Abstract: The centrepiece of this analytical review is the metabolism of hydroxyapatite in its natural, bone, and synthetic forms, where the mitochondria-mediated mechanism may serve as the leading mechanism. The possibility that osteoblast mitochondria play an important role in the initial stages of bone mineralisation is discussed. Furthermore, the paper highlights the key role of mitochondria in the metabolism of synthetic hydroxyapatite.Differences between the results of in vivo and in vitro studies using synthetic hydroxyapatite of different morphologies are also detailed. It is noted that long-term infiltration with immune cells and in vivo studies are necessary to adequately evaluate hydroxyapatite as a bone-plastic material.Particular attention is given to the interaction of hydroxyapatite with immune cells and its ability to affect the ribosomes and mitochondria of cells. Due to its mechanical properties, scalability and potential use for the treatment of extensive bone defects of tumor origin, hydroxyapatite is a promising material.This study also highlights the importance of further development of in vitro research methods in the context of their biomimeticity. Overall, this work offers a theoretical direction for future studies of hydroxyapatite as a bone grafting material and emphasises the value of in vivo studies.

The first 1000 days of life is a critical period that contributes significantly to the programming of an individual's future health. Among the many changes that occur during this period, there is growing evidence that the establishment of a healthy gut microbiota early in life plays an important role in the prevention of both short- and long-term health problems. Numerous publications suggest that the quality of gut microbiota colonization depends on several dietary factors, including breastfeeding. In this respect, a relationship between breastfeeding and the risk of inflammatory bowel disease (IBD) has been suggested. IBD are chronic intestinal diseases in which perinatal factors may be partly responsible for its onset. We propose to review the existence of links between breastfeeding and IBD, based on experimental and clinical studies. Overall, despite encouraging experimental data in rodents, the association between breastfeeding and the development of IBD remains controversial in humans, partly due to considerable heterogeneity between clinical studies. The duration of exclusive breastfeeding is probably decisive for its lasting effect on IBD. Thus, specific improvements in our knowledge could support dietary interventions targeting the gut microbiome, such as the early use of prebiotics, probiotics or postbiotics in order to prevent the disease.

The targeting-Her-2/neu therapy by passive application with trastuzumab is associated with acquired resistance and subsequent metastasis development, attributed to upregulation of tumoral PD-L1 expression and downregulation of Her-2/neu. We aimed to investigate this association, following active immunization with our recently constructed B cell–peptide based Her-2/neu vaccines in both preclinical and clinical settings. Immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and combined positive score (CPS), were applied to evaluate Her-2/neu and PD-L1 expression using a murine syngeneic tumor model for Her-2/neu lung metastases, and tumor biopsies from a gastric cancer patient with disease progression. A significant and concomitant reduction of Her-2/neu and upregulation of PD-L1 expression was observed in the vaccinated mice, after 7 but not after 4 weeks of metastases development. A significant increase of tumor-infiltrating B lymphocytes was observed at both time points. Downregulation of Her-2/neu and upregulation of PD-L1 were observed in a patient’s primary tumor at the disease progression time point but not prior to vaccination (Her-2/neu IHC: 3 to 0, FISH: 4.98 to 1.63; PD-L1 CPS: 0% to 5%). Our results further underline the need for combination therapy by targeting PD-L1 to prevent metastasis formation and immune evasion of Her-2/neu positive and PD-L1 negative tumor cells.

SARS-CoV-2 infection can lead to life-threatening clinical manifestations. Patients with cardiovascular disease (CVD) are at higher risk for severe courses of COVID-19. However, strategies to predict the course of SARS-CoV-2 infection in CVD patients at the time of hospital admission are still missing. Here, we investigated whether this prediction is achievable by prospectively analysing the blood immunophenotype of 94 participants, including 20 uninfected and 37 acutely SARS-CoV-2-infected CVD patients and 37 healthy donors, using a 36-colour spectral flow cytometry panel. Unsupervised data analysis revealed little differences between healthy donors and CVD patients, whereas the distribution of the cell populations changed dramatically in SARS-CoV-2-infected CVD patients. The latter had more mature NK cells, activated monocyte subsets, central memory CD4+ T cells, and plasmablasts but fewer dendritic cells, CD16+ monocytes, innate lymphoid cells, and CD8+ T cell subsets. Moreover, we identified an immune signature characterised by mucosal-associated invariant T (MAIT) cells, intermediate effector CD8+ T cells, and natural killer T (NKT) cells that is predictive for CVD patients with a severe course of COVID-19. Thus, intensified immunophenotype analyses can help identify patients at risk of severe COVID-19 at hospital admission, improving clinical outcomes through specific treatment.

This study describes the design and development of novel compounds aimed at optimizing the function of microtubules and tubulin in the immune system and the brain as they relate to the Orch OR theory of consciousness. These compounds are defined by the following molecular formulas:C65H100CoN15O22P(C6H12O5);C65H100CoN15O22P(C5H10NO4);(C65H100CoN15O22P)(C6H12N2O)n;(C65H100CoN15O22P)(C6H12O5)(C6H12N2O)n;(C6H12N2O)n(C6H12O5)m;Zn(C6H12O5)2;These molecules, formulated under the form of drugs, health functional foods, or food supplements, have the potential to positively affect a number of areas ranging from prevention and therapy of neurological diseases to supporting the immune system.

High-temperature cooking process like frying, baking, smoking, or drying can induce chemical transformations in conventional food ingredients, causing deteriorative modifications. These reactions, including hydrolytic, oxidative, and thermal changes, are a common occurrence and can result in alterations to the food's chemical composition. In this study, a combination of sucrose and histidine (Su-Hi) was transformed through a process of charring or pyrolysis. The GC-MS profiling study showed that when sucrose and histidine (Su-Hi) are exposed to high temperatures (≈240°C), they produce carbonyl and aromatic compounds including beta-D-Glucopyranose, 1,6-anhydro (10.11 %), 2-Butanone, 4,4-dimethoxy- (12.89 %), 2(1H)-Quinolinone-hydrazine (5.73%), Benzenamine (6.35%), 2,5-Pyrrolidinedione, 1-[(3,4-dimethylbenzoyl)oxy]- (5.82%), Benzene-(1-ethyl-1-propenyl) (5.62%), and 4-Pyridinamine-2,6-dimethyl (5.52%). The compounds mentioned have the ability to permeate the cell membrane and contribute to the development of cell death by necrosis in human immune cells. The evidence available suggests that a specific set of pyrolytic compounds may pose a risk to immune cells. This investigation reveals the complex relationship between high-temperature cooking-induced transformations, compound permeation inside the cells, and downstream cellular responses, emphasizing the significance of considering the broader health implications of food chemical contaminants.

Background：Increasingly, epidemiological surveys and experimental research findings indicate the involvement of immune cells in the onset and progression of prostate cancer. However, it remains unclear whether the relationship between specific immune cell types and prostate cancer is causal or influenced by bias. Through a two-sample Mendelian randomization design, our study aims to uncover the association between different immune cells and the risk of prostate cancer.Methods：A comprehensive study was conducted to investigate the association between immunophenotypes and prostate cancer risk. The study included a total of 731 immunophenotypes as potential exposure factors and analyzed data from 182,625 individuals of European ancestry from the UK Biobank. A screening of 12,097,504 single nucleotide polymorphisms (SNPs) was performed. The main analysis utilized the two-sample Mendelian randomization method with inverse variance weighting (IVW). Additionally, multiple analysis methods were combined, and various tests were conducted to assess heterogeneity and pleiotropy.Results：The resulting study showed a causal relationship between a total of 34 immune phenotypes and prostate cancer. Among them, the four immune phenotypes of CD62L- DC AC, CD19 on sw mem, FSC-A on plasmacytoid DC and HLA DR on monocyte simultaneously meet three or more statistical methods, suggesting a significant causal relationship with prostate cancer. Additionally, among the 34 immunophenotypes, CD28-CD8dim AC was shown to be positive in reverse Mendelian randomization. Most of these cell phenotypes have been reported to be potentially associated with prostate cancer.Conclusions：Our study demonstrates a causal link between immune cells and prostate cancer risk. Filled in the possible roles of all current immune cell pathways in the development and progression of prostate cancer. The next step is to verify the content and influencing mechanism of these immune phenotypes in cancer cells and adjacent cells through experiments, so as to provide new ideas and methods for the prevention and treatment of prostate cancer.

Multiple Sclerosis (MS) is a neurodegenerative disease that mainly affects young adults. The high prevalence of the disease and its impact on patients' quality of life led to priority being given to the etiopathogenesis of the disease to identify possible modifiable factors and consequent effective intervention strategies. Recent hypotheses suggest that the etiopathogenesis of MS is multifactorial and includes factors related to the immune system, neuroinflammation and neuro-degeneration. In this scenario, sleep has a close - although indirect - relationship with MS, through its relationship with each of those factors. In particular, the role of cytokines in immune system impairment and neuroinflammation, mitochondrial dysfunction and oxidative stress in neurodegeneration all are associated with sleep in different forms. Furthermore, melatonin in relation with vitamin D has a potential therapeutic effect in MS sleep-related problems. Given the growing interest of research in the mechanisms underlying MS and therapies able to alleviate MS-related symptoms at all stages of the disease, a more in-depth study of the role of sleep disturbances and the factors intrinsically related to sleep and MS could be useful both to investigate the etiopathogenetic factors of MS and to develop potential non-invasive intervention strategies for MS treatment.

CD147/Basigin, a transmembrane glycoprotein belonging to the immunoglobulin super family, is a multifunctional molecule with various binding partners. CD147 binds to monocarboxylate transporters (MCTs) and supports their expression on plasma membranes. MCTs play an important role in glycolysis, the enzymatic conversion of glucose to pyruvate and adenosine triphosphate (ATP). Pyruvate is further converted to lactic acid which is exported from the cytoplasm by MTC-1 and MCT-4 to maintain intracellular pH and a stable metabolic state. Under physiological conditions, cellular energy production is induced by mitochondrial oxidative phosphorylation. Glycolysis usually occurs under anaerobic conditions, whereas cancer cells depend on glycolysis under aerobic conditions. T cells also require glycolysis for differentiation, proliferation, and activation. Human malignant melanoma cells expressed higher levels of MCT-1 and MCT-4, co-localized with CD147 on the plasma membrane and showed an increased glycolysis rate compared to normal human melanocytes. Silencing of CD147 by siRNA abrogated the membrane expression of MCT-1 and MCT-4 and disrupted glycolysis, inhibiting cancer cell activity. The differentiation of CD4+ T cells into Th17 cells is a pivotal process in the development of various immune disorders, including psoriasis. Studies using CD147-deficient mice demonstrated the involvement of CD147 in psoriasis. MCT-1 was absent on CD4+ T cells in CD147-deficient mice. Naïve CD4+ T-cells from CD147-deficient mice show low potential for differentiation into Th17 cells. Imiquimod-induced skin inflammation was significantly milder in CD147-deficient mice than in wild-type mice. These findings indicate that CD147/Basigin is involved in the development of malignant tumors and T cell mediated immunological disorders via regulation of glycolysis.

Repeated exposure to pathogens leads to evolutionary selection of adaptive traits. Many species transfer immunological memory to their offspring to counteract future immune challenges. Transfer factor such as that found in colostrum is among the many mechanisms where transfer of immunologic memory from one generation to the next can be achieved for enhanced immune response. Here, a library of 100 plants with high protein contents were screened to find plant-based proteins that behave like a transfer factor moiety to boost human immunity. Aqueous extracts from candidate plants were tested on a human peripheral blood mononuclear cell (PBMC) cytotoxicity assay using human cancerous lymphoblast cells - K562 cells as a target and Natural Killer cells as an effector. Plant extracts that caused PBMCs to exhibit enhanced killing beyond the capability of the colostrum-based transfer factor were considered hits. Primary screening yielded an 11% hit rate. Protein content of these hits were tested by Bradford Assay and Coomassie stained-SDS-PAGE, where three extracts were confirmed to have high protein contents. Plants with high protein contents underwent C18 column fractionation using methanol gradients followed by membrane ultrafiltration to isolate proteins with molecular weight &lt;3 kDa, 3-30 kDa, and &gt;30 kDa fractions. It was found that the 3-30 kDa and &gt;30 kDa fractions had high activity in the PBMC cytotoxicity assay. The 3-30 kDa ultrafiltrates from the top two hits, seeds from Raphanus sativus and Brassica juncea, were then selected for protein identification by mass spectrometry. The majority of the proteins in the fractions were found to be seed storage proteins, with low abundance of proteins involved in plant defense and stress response. These findings suggest that Raphanus sativus or Brassica juncea extracts could be considered for further characterization and immune functional exploration with a possibility of supplemental use to bolster recipients’ immune response.

In the present study, bivalent nanovaccines of S. iniae and F. covae were administered by immersion vaccination at 30 and 40 days after hatching (DAH), and the third vaccination was orally administered by feeding at 50 DAH. Five different groups were designed: group 1 was set as the control group, and groups 2-4 were vaccinated using the same protocols. ELISA revealed that the levels of total IgM and specific IgM to S. iniae, and F. covae were significantly elevated in groups 2-4 at 10, 20, and 30 days after vaccination (DAV). A qRT‒PCR analysis of immune-related genes revealed significantly higher IgT expression in the vaccinated groups compared with the control group, as revealed by 44-100-fold changes in the vaccinated groups compared with the control (p &lt; 0.001) at every tested time point after vaccination. All vaccinated groups expressed IgM, MHCIIα and TCRα at significantly higher levels than the control group at 10 and/or 20 DAV (p &lt; 0.05). In the S. iniae challenge tests, the survival of vaccinated groups 2-4 ranged from 62.15 ± 2.11 to 75.70 ± 3.36%, which significantly differed from that of the control group (44.44 ± 1.92%). Similarly, all vaccinated groups showed higher survival rates of 68.89 ± 3.85 to 77.78 ± 5.09% during F. covae challenge than the control groups (50.00 ± 3.33%) (p &lt; 0.05).