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Carcinoembryonic antigen‐related cell adhesion molecule 1 (CEACAM1) is a membrane protein that plays an important role in a variety of immune and non‐immune functions. Such functions are regulated by its activity as a homophilic ligand but also through its ability to interact as a heterophilic ligand with various host proteins. These include CEACAM5, T cell immunoglobulin‐mucin like protein‐3 (TIM‐3) and, potentially, protein death protein 1 (PD‐1). Furthermore, CEACAM1 is targeted by various pathogens to allow them to invade a host and bypass an effective immune response. Clinically, CEACAM1 plays an important role in infectious diseases, autoimmunity and cancer. In this review, we describe the structural basis for CEACAM1 interactions as a homophilic and heterophilic ligand. We discuss the regulation of its monomeric, dimeric and oligomeric states in cis and trans binding as well as the consequences for eliciting downstream signalling activities. Furthermore, we explore the potential role of avidity in determining CEACAM1's activities. [ABSTRACT FROM AUTHOR]

In recent years, zinc oxide nanoparticles (ZnO NPs) have gained attention as feed additives due to their high bioavailability. However, research on their impact on fish growth and health is limited. To investigate the influences of dietary addition of ZnO NPs on growth performance and immune function of rare minnow, rare minnows were fed diets with different ZnO NPs content. Growth analysis showed that ZnO NPs had a negative effect on the weight of rare minnow, decreasing and then increasing condition factors (CFs) and specific growth rate. Additionally, the accumulated zinc (Zn) level was significantly higher (p < 0.05), and the liver injury index was significantly higher (p < 0.05) in the dietary ZnO NPs group compared to the control group. The number of erythrocytes and leukocytes in blood samples increased and then decreased after treatment with ZnO NPs. It was further found that ZnO NPs as a dietary supplement significantly increased the Zn content and markedly repressed the expression of growth‐related genes after 60 days of accumulation in muscle tissues, and accumulation in liver tissues for 60 days significantly enhanced the expression of immune modulation–related genes expression (p < 0.05). The findings suggested that short‐term supplementation of ZnO NPs could positively affect fish growth and immune function. However, prolonged supplementation of dietary ZnO NPs resulted in reduced body weight and compromised immune function owing to the buildup of Zn in different tissues. [ABSTRACT FROM AUTHOR]

ABSTRACT Genetic variation that impacts gene regulation, rather than protein function, can have strong effects on trait variation both within and between species. Epigenetic mechanisms, such as DNA methylation, are often an important intermediate link between genotype and phenotype, yet genetic effects on DNA methylation remain understudied in natural populations. To address this gap, we used reduced representation bisulfite sequencing to measure DNA methylation levels at 555,856 CpGs in peripheral whole blood of 573 samples collected from free‐ranging rhesus macaques (Macaca mulatta) living on the island of Cayo Santiago, Puerto Rico. We used allele‐specific methods to map cis‐methylation quantitative trait loci (meQTL) and tested for effects of 243,389 single nucleotide polymorphisms (SNPs) on local DNA methylation levels. Of 776,092 tested SNP–CpG pairs, we identified 516,213 meQTL, with 69.12% of CpGs having at least one meQTL (FDR < 5%). On average, meQTL explained 21.2% of nearby methylation variance, significantly more than age or sex. meQTL were enriched in genomic compartments where methylation is likely to impact gene expression, for example, promoters, enhancers and binding sites for methylation‐sensitive transcription factors. In support, using mRNA‐seq data from 172 samples, we confirmed 332 meQTL as whole blood cis‐expression QTL (eQTL) in the population, and found meQTL–eQTL genes were enriched for immune response functions, like antigen presentation and inflammation. Overall, our study takes an important step towards understanding the genetic architecture of DNA methylation in natural populations, and more generally points to the biological mechanisms driving phenotypic variation in our close relatives. [ABSTRACT FROM AUTHOR]

Demand for sustainable animal and aquaculture production drives the exploration of novel feed additives. We highlight octacosanol, a long‐chain alcohol from plant sources, as a promising multifunctional feed additive. The review comprehensively evaluates octacosanol's applications in animal and aquaculture nutrition, including its molecular properties and mechanisms of action. It elucidates how octacosanol affects lipid metabolism, energy utilization and immune modulation. Octacosanol enhances livestock growth, efficiency, carcass quality and stress resilience. We thoroughly discuss how it enhances feed utilization, disease resistance and overall performance in finfish and shellfish in aquaculture. The review also addresses the ecological and sustainability aspects of octacosanol utilization. We identify challenges and knowledge gaps in octacosanol research, prompting suggestions for future investigations. We address regulatory considerations, dosage optimization and potential interactions with other feed additives to ensure the safe and effective use of octacosanol. In conclusion, the review highlights octacosanol's potential as a versatile feed additive in the animal and aquaculture industries and urges further research to uncover its benefits and sustainability contributions, proposing a prospective research plan for this purpose. This thorough analysis is a valuable resource for researchers, nutritionists and industry professionals looking to find innovative methods to improve production practices and advance sustainable food systems. [ABSTRACT FROM AUTHOR]

Aim: The study aimed to elucidate the clinical efficacy of colonoscopy combined with laparoscopic radical resection for patients with colon cancer. Methods: Cases with colon cancer were divided into the control group (received laparoscopic radical resection) and the experimental group (received colonoscopy combined with laparoscopic radical resection). Inflammatory cytokines' levels and immune functions were evaluated before and after the operation. The 36‐item Short Form Health Survey (SF‐36) was used to evaluate the living quality. Results: Relative to the control group, individuals in the experimental group had a shorter hospital stay and post‐operative anal exhaust, and reduced intraoperative blood loss. Changes in serum interferon‐gamma (IFN‐γ), interleukin‐8 (IL‐8) and IL‐10 levels were minimal in the experimental group. Serum CD3+%, CD4+% and CD4+/CD8+ values of the two groups were significantly decreased compared with the preoperative values, which increased more significantly in the experimental group relative to the control group. After the operation, individuals in the experimental group presented higher SF‐36 scores than those in the experimental group. The experimental group presented a low incidence of post‐operative complications. Conclusions: Colonoscopy combined with laparoscopic radical resection for colon cancer had only a little effect on immune function and inflammatory response. It can shorten the recovery time of patients and reduce post‐operative complications, which is worthy of further clinical promotion. [ABSTRACT FROM AUTHOR]

Summary: Sickle cell anaemia (SCA) patients display elevated levels of circulating pro‐inflammatory cytokines and endothelial activation markers compared to healthy peers. The impact of exercise on the pro‐inflammatory state in SCA remains unclear. This study aimed to characterize the whole‐blood transcriptome profile in response to an acute bout of exercise in paediatric SCA patients. Twenty‐three SCA participants (13 ± 3 years, 52% girls) and 17 healthy controls (14 ± 3 years, 29% girls) performed eight 2‐min bouts of cycle ergometry interspersed with 1‐min rest intervals. Whole‐blood transcriptome profile (RNA‐seq) was performed before and after exercise. At baseline, gene pathways associated with gas transport in erythrocytes were up‐regulated in SCA patients compared to controls. Following exercise, gene pathways associated with innate immunity were altered in both groups. Interaction analyses revealed 160 annotated genes (101 up‐ and 59 down‐regulated) that differentially altered by exercise in SCA patients. Moreover, genes that exhibited a blunted response to exercise in SCA patients were enriched in the IL‐17 signalling pathway, suggesting an impaired innate immune response to exercise. This data will contribute to the development of evidence‐based exercise prescription guidelines for this patient population. [ABSTRACT FROM AUTHOR]

This article highlights the advances in mast cell research in 2023. It discusses the growing understanding of mast cell heterogeneity and interactions through single cell RNA sequencing studies. The article also explores the role of mast cells in the central nervous system and their involvement in host defense against SARS-CoV-2 infection. The research reveals the complexity and impact of mast cells in various tissues and emphasizes their diverse functions in immune defense, inflammation, and allergic disease. Additionally, the article discusses the role of mast cells in antigen-avoidance behaviors, commensal bacteria tolerance, and the regulation of cilia in the brain. The findings suggest potential therapeutic avenues for conditions such as tumor-associated hydrocephalus and COVID-19. Overall, the research underscores the critical importance of mast cells in immune-mediated damage prevention and their collaboration with other host defense mechanisms. [Extracted from the article]

Migratory birds may either upregulate their immune system during migration as they might encounter novel pathogens or downregulate their immune system as a consequence of trade‐offs with the resource costs of migration. Support for the latter comes not least from a study that reports a positive correlation in autumn migrating birds between fuel stores and parameters of innate and acquired immune function, that is, energy‐exhausted migrants appear to have lowered immune function. However, to our knowledge, no study has tested whether this pattern exists in spring migrating birds, which may face other trade‐offs than autumn migrants. Here, we investigate if in spring there is a relationship between fuel stores and microbial‐killing ability, a measure of innate immune function, and total immunoglobulin (IgY), a measure of acquired immune function, in four migrating bird species: chaffinches (Fringilla coelebs), dunnocks (Prunella modularis), song thrushes (Turdus philomelos) and northern wheatears (Oenanthe oenanthe). Our findings indicate no significant correlation between fuel stores and either microbial killing ability or IgY levels when considering all species collectively. When analysing species separately, we found a significant negative correlation between fuel stores and microbial‐killing ability in chaffinches and a positive correlation between fuel stores and IgY levels in wheatears. In song thrushes, but not in any of the other species, there was a significant negative correlation between relative arrival date and microbial‐killing ability and between arrival date and IgY levels. Sex did not affect immune function in any of the species. Our study suggests that the relationship between immune function and fuel stores may be different during spring migration compared to autumn migration. Differences in the speed of migration or pathogen pressure may result in different outcomes of the resource trade‐off between investment in immune function and migration among the seasons. [ABSTRACT FROM AUTHOR]

Objectives: Sleep disturbance is common in autoimmune rheumatism diseases (ARD) and it plays an important role in activating disease and affects the quality of life. This study aims to evaluate the efficacy and acceptability of the novel electrical therapy on sleep disturbance in ARD patients and its effect on immunologic factors. Methods: A total of 51 ARD patients (26 treatment group and 25 control group) with sleep disturbance were enrolled in this study. Sleep parameters and immunological indicators (serum level of 12 cytokines and immune function) were collected. The novel electrical therapy was prescribed for 15–30 min 3–6 times a day. The Pittsburg Sleep Index (PSQI) was assessed before and after 3 months' treatment by Mi Energy equipment. Immune function and serum levels of cytokines of all participants at baseline and after treatment were tested with flow cytometry and flow immunofluorescence, respectively. Correlation analysis was used to analyze the relationship between sleep disturbance and immunologic factors. Multiple linear regression analysis was employed to investigate the risk of sleep disturbance in ARD. Results: The global score of PSQI (Baseline: 12.81 ± 4.07, After novel electrical therapy: 4.88 ± 2.76) was effectively improved after 3 months of adjuvant therapy by electrical therapy. We also found that serum levels of IL‐8 and IL‐1β statistically significantly decreased after novel electrical therapy. This adjuvant therapy can also significantly decrease the percentage of CD4 + CD8 + T cell, effector memory CD8 + T cell, Memory CD8 + T cell, Th17 cell, and plasma cell and significantly can increase the percentage of naïve CD8 + T cell, Th2 cell, and Tfh2 cell. Nevertheless, all serum level of 12 cytokines and the percentage of immune cells did not correlate with the PSQI global score except the Tc17 cell. Furthermore, age is an independent risk factor influencing PSQI scores (OR = 1.15, p < 0.05) in patients with autoimmune diseases through multiple linear regression analysis. Conclusions: Novel electrical therapy can effectively improve sleep disturbance in patients with ARD. It can also change the serum level of some cytokines (IL‐8 and IL‐1β) and percentage of immune cells (CD4 + CD8 + T cell, effector memory CD8 + T cell, Memory CD8 + T cell, Th17 cell, naïve CD8 + T cell, Th2 cell, Tfh2 cell, and plasma cell). [ABSTRACT FROM AUTHOR]

Objective: This study aimed to link intracellular adenosine triphosphate content in CD4+ T lymphocytes (CD4+ iATP) with sepsis patient mortality, seeking a new predictive biomarker for outcomes and enhanced management. Methods: 61 sepsis patients admitted to the Intensive Care Unit between October 2021 and November 2022 were enrolled. iATP levels were gauged using whole blood CD4+ T cells stimulated with mitogen PHA‐L. Based on CD4+ iATP levels (<132.24 and ≥132.24 ng/mL), patients were categorized into two groups. The primary endpoint was all‐cause mortality. To identify factors associated with mortality, both univariate and multivariate Cox proportional hazard analyses were conducted. Results: Of the patients, 40 had high CD4+ iATP levels (≥132.24 ng/mL) and 21 had low levels (<132.24 ng/mL). In a 28‐day follow‐up, 21 (34.4%) patients perished. Adjusting for confounders like SOFA score, APACHE II score, lactic acid, and albumin, those with low CD4+ iATP had three‐ to fivefold higher mortality risk compared to high CD4+ iATP patients (61.9% vs. 20.0%; hazard ratio [95% confidence interval], Model 1: 4.515 [1.276–15.974], p =.019, Model 2: 3.512 [1.197–10.306], p =.022). CD4+ iATP correlated positively with white blood cell and neutrophil counts but not with lymphocytes, CD3, and CD4 counts. Conclusions: Low CD4+ iATP levels were associated with a higher risk of mortality in sepsis patients. Measurement of CD4+ iATP may serve as a useful tool for identifying patients at a higher risk of mortality and could potentially provide a basis for clinical treatment. Further research is warranted to fully elucidate the underlying mechanisms of this association. [ABSTRACT FROM AUTHOR]

Summary: Understanding sex differences in immunological responses in the context of obesity is important to improve health outcomes. This systematic review aimed to investigate sex differences in systemic inflammation, immune cell phenotype, and function in diet‐induced obesity (DIO) animal models. A systematic search in Medline, Embase, and CINAHL from inception to April 2023 was conducted, using a combination of the following concepts: sex, obesity, cytokines, and immune cell phenotypes/function. Forty‐one publications reporting on systemic inflammation (61%), cell phenotype (44%), and/or function (7%) were included. Females had lower systemic inflammation compared with males in response to DIO intervention and a higher proportion of macrophage (M)2‐like cells compared with males that had a higher proportion of M1‐like in adipose tissue. Although there were no clear sex differences in immune function, high‐fat DIO intervention remains an important factor in the development of immune dysfunction in both males and females, including disturbances in cytokine production, proliferation, and migration of immune cells. Yet, the mechanistic links between diet and obesity on such immune dysfunction remain unclear. Future studies should investigate the role of diet and obesity in the functionality of immune cells and employ adequate methods for a high‐quality investigation of sex differences in this context. [ABSTRACT FROM AUTHOR]

Genetic selection for milk production traits in US Holsteins has affected numerous genes associated with reproduction and immunity. This study compares the transcriptomic response of peripheral blood mononuclear cells to an in vitro Brucella abortus strain RB51 (RB51) bacterial challenge between contemporary Holsteins and Holsteins that have not been selected for milk production traits since the mid‐1960s. Total RNA was extracted from peripheral blood mononuclear cells from four contemporary and four unselected lactating, primiparous cows following 24‐h incubation with or without stimulation with RB51 bacteria. RNA was sequenced and reads analyzed using tools from galaxy.scinet.usda.gov. A total of 412 differentially expressed genes (false discovery rate p < 0.05, log fold change > |1|) were identified. The upregulated genes (genes with higher expression in contemporary than unselected cattle) were enriched for 19 terms/pathways, including alanine, aspartate, and glutamate metabolism, indicating a cellular stress response. Downregulated genes (genes with higher expression in unselected than contemporary cows) were enriched for 37 terms/pathways, representing diverse immune responses, including natural killer cell‐mediated immunity, interferon‐γ production, negative regulation of interleukin‐10 production, and cytokine receptor activity indicating a broad immune response with an emphasis on immune defense. These results provide evidence that differences exist between the two genotypes in response to in vitro bacterial challenge. This suggests that contemporary cows, genetically selected for milk production, may have reduced immune function, including limitations in response to intracellular bacteria. [ABSTRACT FROM AUTHOR]

One carbon (1C) metabolism is critical for cellular viability and physiological homeostasis. Starting from its crucial involvement in purine biosynthesis to posttranslational modification of proteins, 1C metabolism contributes significantly to the development and cellular differentiation through methionine and folate cycles that are pivotal for cellular function. Genetic polymorphisms of several genes of these pathways are implicated in disease pathogenesis and drug metabolism. Metabolic products of 1C metabolism have significant roles in epigenetic modifications through DNA and histone protein methylation. Homocysteine is a product that has clinical significance in the diagnosis and prognosis of several critical illnesses, including chronic immune diseases and cancers. Regulation of the function and differentiation of immune cells, including T‐cells, B‐cells, macrophages, and so forth, are directly influenced by 1C metabolism and thus have direct implications in several immune disease biology. Recent research on therapeutic approaches is targeting nuclear, cytoplasmic, and mitochondrial 1C metabolism to manage and treat metabolic (i.e., type 2 diabetes), neurodegenerative (i.e., Alzheimer's disease), or immune (i.e., rheumatoid arthritis) diseases. 1C metabolism is being explored for therapeutic intervention as a common determinant for a spectrum of immune and metabolic diseases. Identifying the association or correlation between essential metabolic products of this pathway and disease onset or prognosis would further facilitate the clinical monitoring of diseases. Significance statement: One‐carbon (1C) metabolism is critical for cellular biochemical properties and physiology.A malfunction of 1C metabolism disrupts immune cell functions implicated in disease pathology.Recent studies are exploiting the re‐wiring of 1C metabolism for therapeutic interventions for chronic diseases. [ABSTRACT FROM AUTHOR]

Background: IgE‐mediated sensitisation to egg is common in infants. In some cases, the processes leading to egg sensitisation are established in early life, even before introduction to solid foods. The underlying mechanisms remain poorly understood. Methods: We performed detailed immune cell phenotyping of peripheral blood mononuclear cells and determined in vitro cytokine responses following allergen specific and non‐specific immune stimulation. To determine if unique immune profiles were linked to early‐life egg sensitisation, we compared 92 infants at 4–6 months of age, with (EggCAP+, n = 41) and without (EggCAP−, n = 51) early egg sensitisation. Additionally, 47 cord blood samples were analysed. For a subset of participants (n = 39), matching cord blood mononuclear cells were assessed by flow cytometry to establish the impact of IgE sensitisation on immune developmental trajectories. Results: EggCAP+ infants were found to exhibit a unique immune phenotype characterised by increased levels of circulating CD4+ T regulatory cells (Treg), CD4+ effector memory (EM) Treg and increased expression of the IgE receptor, FcεR1, on basophils. The increased CD4+ EM Treg profiles were already present in cord blood samples from EggCAP+ infants. A general Th2‐skewing of the immune system was observed based on increased IL‐13 production following phytohemagglutinin stimulation and by comparing immune developmental trajectories, EggCAP+ infants displayed an expansion of basophils and reduced levels of CD4− T cells compared to EggCAP− infants. Conclusions: Immunological profiles associated with egg sensitisation are detectable in infant circulation at 4–6 months of age and at birth. Understanding the immune mechanisms underlying early‐life sensitisation could provide important insights for future food allergy prevention strategies. [ABSTRACT FROM AUTHOR]

By 2100, greenhouse gases are predicted to reduce ozone and cloud cover over the tropics causing increased exposure of organisms to harmful ultraviolet‐B radiation (UVBR). UVBR damages DNA and is an important modulator of immune function and disease susceptibility in humans and other vertebrates. The effect of UVBR on invertebrate immune function is largely unknown, but UVBR together with ultraviolet‐A radiation impairs an insect immune response that utilizes melanin, a pigment that also protects against UVBR‐induced DNA damage. If UVBR weakens insect immunity, then it may make insect disease vectors more susceptible to infection with pathogens of socioeconomic and public health importance. In the tropics, where UVBR is predicted to increase, the mosquito‐borne dengue virus (DENV), is prevalent and a growing threat to humans. We therefore examined the effect of UVBR on the mosquito Aedes aegypti, the primary vector for DENV, to better understand the potential implications of increased tropical UVBR for mosquito‐borne disease risk. We found that exposure to a UVBR dose that caused significant larval mortality approximately doubled the probability that surviving females would become infected with DENV, despite this UVBR dose having no effect on the expression of an effector gene involved in antiviral immunity. We also found that females exposed to a lower UVBR dose were more likely to have low fecundity even though this UVBR dose had no effect on larval size or activity, pupal cuticular melanin content, or adult mass, metabolic rate, or flight capacity. We conclude that future increases in tropical UVBR associated with anthropogenic global change may have the benefit of reducing mosquito‐borne disease risk for humans by reducing mosquito fitness, but this benefit may be eroded if it also makes mosquitoes more likely to be infected with deadly pathogens. [ABSTRACT FROM AUTHOR]

Objectives: Tattooing is not an evolved behavior, but it may be a phenotypic gambit to highlight immunological health. Phenotypic gambits are traits or behaviors that appear costly but occur at high rates as a honing process of natural selection not constrained by genetics. Tattooing is an ancient practice that is increasing in popularity worldwide, but it involves wounding the body, which seems counterintuitive because it challenges the immune system and makes one more susceptible to infection. But tattooing may represent a costly honest signal of fitness by "upping the ante" in an era of hygiene or a means to stimulate the immune system in a way that improves and highlights underlying fitness. Materials and Methods: We investigated this hypothesis by assessing bacteria killing activity (BKA) in saliva samples collected during two studies of tattooing (N = 40). We compared previous tattoo experience (extent of body tattooed and hours spent being tattooed) to BKA before and after getting a new tattoo. Results: Tattoo experience positively predicts post‐tattoo BKA (β = 0.48, p = 0.01), suggesting that people with more tattoo experience have a relatively more immediate and active immune response than those with less tattoo experience. Discussion: Tattoo experience may elevate innate immunological vigilance, which could aid in protecting against future dermal insults. [ABSTRACT FROM AUTHOR]

Keratinocytes are the predominant cell type in the skin epidermis, and they not only protect the skin from the influence of external physical factors but also function as an immune barrier against microbial invasion. However, little is known regarding the immune defence mechanisms of keratinocytes against mycobacteria. Here, we performed single‐cell RNA sequencing (scRNA‐seq) on skin biopsy samples from patients with Mycobacterium marinum infection and bulk RNA sequencing (bRNA‐seq) on M. marinum‐infected keratinocytes in vitro. The combined analysis of scRNA‐seq and bRNA‐seq data revealed that several genes were upregulated in M. marinum‐infected keratinocytes. Further in vitro validation of these genes by quantitative polymerase chain reaction and western blotting assay confirmed the induction of IL‐32 in the immune response of keratinocytes to M. marinum infection. Immunohistochemistry also showed the high expression of IL‐32 in patients' lesions. These findings suggest that IL‐32 induction is a possible mechanism through which keratinocytes defend against M. marinum infection; this could provide new targets for the immunotherapy of chronic cutaneous mycobacterial infections. [ABSTRACT FROM AUTHOR]

Introduction: This study endeavored to investigate the role of DOCK8 in modulating the immune function triggered by sepsis. Methods: Expression of DOCK8 in the whole blood of sepsis patients and its enrichment pathways were assayed by bioinformatics. Pearson analysis was used to predict the relationship between glycolytic signaling pathway and its relevance to neutrophil function in sepsis. A sepsis mouse model was then built by performing cecal ligation and puncture treatment on male mice. Neutrophils were isolated, and their purity was tested by flow cytometry. Neutrophils were then stimulated by lipopolysaccharide to build a sepsis cell model. Next, quantitative reverse transcription polymerase chain reaction and CCK‐8 were applied to test the expression of DOCK8 and cell viability, western blot to assay the expression of HK‐2, PKM2, and LDHA proteins, ELISA to measure the concentrations of TNF‐α, IL‐1β, and IL‐6, Transwell to detect the chemotaxis of neutrophils and flow cytometry to detect the phagocytic activity of neutrophils. Finally, in different treatment groups, we used Seahorse XF 96 to analyze the extracellular acidification rate (ECAR) of sepsis cells and used enzyme‐linked immunosorbent assay to detect the contents of pyruvic acid, lactic acid, and ATP in sepsis cells. Results: DOCK8 was downregulated in sepsis blood and activated neutrophils. Aerobic glycolysis was positively correlated with sepsis. Activated neutrophils promoted the expression of inflammatory factors TNF‐α, IL‐1β, and IL‐6. Low expression of DOCK8 facilitated the proliferation, chemotaxis, and phagocytic activity of sepsis cells and promoted the expression of inflammatory factors. Bioinformatics analysis revealed that DOCK8 was enriched in the glycolytic signaling pathway. Low expression of DOCK8 induced ECAR, promoted the protein expression of HK‐2, PKM2 and LDHA, and favored the increase of pyruvate, lactate, and ATP contents. While 2‐DG treatment could restore these effects. Conclusion: DOCK8 may inhibit sepsis‐induced neutrophil immune function by regulating aerobic glycolysis and causing excessive inflammation, which helps to explore potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Ecological carryover effects, or delayed effects of the environment on an organism's phenotype, are central predictors of individual fitness and a key issue in conservation biology. Climate change imposes increasingly variable environmental conditions that may be challenging to early life‐history stages in animals with complex life histories, leading to detrimental physiological and fitness effects in later life. Yet, the latent nature of carryover effects, combined with the long temporal scales over which they can manifest, means that this phenomenon remains understudied and is often overlooked in short‐term studies limited to single life‐history stages. Herein, we review evidence for the physiological carryover effects induced by elevated ultraviolet radiation (UVR; 280–400 nm) as a potential contributor to recent amphibian population declines. UVR exposure causes a suite of molecular, cellular and physiological consequences known to underpin carryover effects in other taxa, but there is a lack of research linking embryonic and larval UVR exposures to fitness consequences post‐metamorphosis in amphibians. We propose that the key impacts of UVR on disease‐related amphibian declines are facilitated through carryover effects that bridge embryonic and larval UVR exposure with potential increased disease susceptibility post‐metamorphosis. We conclude by identifying a practical direction for the study of ecological carryover effects in amphibians that could guide future ecological research in the broader field of conservation physiology. Only by addressing carryover effects can many of the mechanistic links between environmental change and population declines be elucidated. [ABSTRACT FROM AUTHOR]

Objective: This work was implemented to elucidate the miR‐126‐5p expression in the plasma of patients with sepsis‐induced acute lung injury (ALI) and its correlation with inflammation and immune function. Methods: The peripheral blood of patients with sepsis‐induced ALI was obtained, and the levels of inflammatory factors (interleukin‐6 [IL‐6], C‐reactive protein [CRP], and procalcitonin [PCT]) were determined. Meanwhile, T lymphocyte subsets (CD3+, CD4+, and CD8+), and immunoglobulins (IgA, IgM, and IgG) were tested. miR‐126‐5p and TRAF6 mRNA expression in plasma was assessed. Receiver operating characteristic (ROC) curve was performed to assess the diagnostic accuracy of miR‐126‐5p in sepsis without ALI and sepsis with ALI. Correlation between miR‐126‐5p expression and clinical indicators was analyzed. The targets of miR‐126‐5p were predicted using the bioinformatics method, and the direct targets were verified through investigations. Results: miR‐126‐5p expression in plasma of patients with sepsis‐induced ALI was reduced than that of patients with sepsis without ALI. miR‐126‐5p expression was negatively correlated with IL‐6, CRP, and PCT but positively correlated with IgA, IgM, and IgG as well as CD3+, CD4+, and CD8+ in patients with sepsis‐induced ALI. ROC curve suggested that miR‐126‐5p (AUC: 0.777; 95%CI: 0.689–0.866) could distinguish patients with sepsis with ALI from patients with sepsis without ALI. TRAF6 expression in patients with sepsis‐induced ALI was higher than that in patients with sepsis without ALI. TRAF6 was a target gene of miR‐126‐5p, Conclusion: This research highlights that miR‐126‐5p is reduced in the plasma of patients with sepsis‐induced ALI, and miR‐126‐5p relates to systemic inflammation and immune function indicators. [ABSTRACT FROM AUTHOR]

Background: Probiotics comprise effective feed additives that can replace antibiotics in animal livestock production. However, mono‐strain probiotics appear less effective because of their instability. Therefore, the present study aimed to investigate dietary supplementation with compound probiotics (CPP) on growth performance, diarrhea rate and intestinal mucosal barrier, as well as the possible molecular mechanism, in chicks. In total, 360 1‐day‐old chicks of the Hy‐Line Brown Chicks were randomly divided into the control group (CON, basal diet), chlortetracycline group (500 mg kg−1 CTC) and compound probiotics group (1000 mg kg−1 CPP, consisting of Bacillus subtilis, Bacillus licheniformis, Enterococcus faecium and yeast). The experiment period was 56 days. Results: The results showed that, in comparison with the CON group, CPP significantly increased the average daily feed intake and average daily gain of chicks and reduced diarrhea (P < 0.05). The probiotic group exhibited increased immune organ (i.e. spleen and thymus) mass and increased levels of serum immunoglobulin (Ig)A, IgM and IgG (P < 0.05) compared to the CTC group. In addition, the jejunal mass and morphology were improved in the probiotic group (P < 0.05). Moreover, CPP reinforced jejunal barrier function, as indicated by increased transepithelial electrical resistance, protein expression of occludin and claudin‐1, and diamine oxidase levels in the jejunum (P < 0.05). Likewise, enhanced fluorescence signals of proliferating cell nuclear antigen‐labeled mitotic cells and villin‐labeled absorptive cells in the jejunum (P < 0.05) suggested that CPP promoted intestinal stem cells activity. Mechanistically, the Wnt/β‐catenin signaling pathway, including β‐catenin, TCF4, c‐Myc, cyclin D1 and Lgr5, was amplified in the jejunum by CPP addition (P < 0.05). Conclusion: The present study demonstrated that dietary supplementation with CPP reinforced the jejunal epithelial integrity by activating Wnt/β‐catenin signaling and enhanced immune function in chicks. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Epigenetic ageing, i.e., age‐associated changes in DNA methylation patterns, is a sensitive marker of biological ageing, a major determinant of morbidity and functional decline. We examined the association of physical activity with epigenetic ageing and the role of immune function and cardiovascular risk factors in mediating this relation. Moreover, we aimed to identify novel molecular processes underlying the association between physical activity and epigenetic ageing. We analysed cross‐sectional data from 3567 eligible participants (mean age: 55.5 years, range: 30–94 years, 54.8% women) of the Rhineland Study, a community‐based cohort study in Bonn, Germany. Physical activity components (metabolic equivalent (MET)‐Hours, step counts, sedentary, light‐intensity and moderate‐to‐vigorous intensity activities) were recorded with accelerometers. DNA methylation was measured with the Illumina HumanMethylationEPIC BeadChip. Epigenetic age acceleration (Hannum's age, Horvath's age, PhenoAge and GrimAge) was calculated based on published algorithms. The relation between physical activity and epigenetic ageing was examined with multivariable regression, while structural equation modeling was used for mediation analysis. Moreover, we conducted an epigenome‐wide association study of physical activity across 850,000 CpG sites. After adjustment for age, sex, season, education, smoking, cell proportions and batch effects, physical activity (step counts, MET‐Hours and %time spend in moderate‐to‐vigorous activities) was non‐linearly associated with slower epigenetic ageing, in part through its beneficial effects on immune function and cardiovascular health. Additionally, we identified 12 and 7 CpGs associated with MET‐Hours and %time spent in moderate‐to‐vigorous activities, respectively (p < 1 × 10−5). Our findings suggest that regular physical activity slows epigenetic ageing by counteracting immunosenescence and lowering cardiovascular risk. [ABSTRACT FROM AUTHOR]

The reactive scope model was created to address two major unanswered questions in stress physiology: how and when does the adaptive acute stress response turn into harmful chronic stress? Previous studies suggest that immunoenhancement should occur in reactive homeostasis (acute stress) and immunosuppression should occur in homeostatic overload (chronic stress). We used this dichotomy of immune function to further elucidate the transition from acute to chronic stress by treating house sparrows (Passer domesticus) with different intensities of chronic stress and then monitoring their immune function. By varying the number of stressors given per day and the length of chronic stress bouts over a period of 6 months, we produced four treatment groups: high, medium, and low stress, and captivity‐only. We tracked immunity through the bacterial killing assay and monitored healing of a 4 mm skin biopsy punch. We hypothesized that higher‐stress birds would repair their skin more slowly and have lower bacterial killing capacity. The opposite was true—high‐stress birds initially repaired their skin fastest. Additionally, all birds dramatically reduced bacterial killing capacity after the biopsy and increased food‐derived uric acid, suggesting increased energy acquisition and a shift in immune resources to a more immediate concern (healing). Once healing finished, only the high‐stress birds were unable to recover circulating immune function, suggesting that the combination of high stress and an immune challenge pushed these birds into homeostatic overload. Prioritizing healing over other immunological processes might be the best defense for a bird in its natural habitat. [ABSTRACT FROM AUTHOR]

BACKGROUND: Sheep whey protein (SWP), Fu brick tea polysaccharides (FBTP) and stachyose (STA) have been shown to improve immunity, but little is known about the regulatory effect of SWP, FBTP, STA and their combined formula (CF) on immune function and intestinal metabolism of immunosuppressed mice induced by cyclophosphamide (CTX). RESULTS: Administration of SWP, FBTP, STA or CF restored the levels of body weight, immune organ index, immune organ morphology, cytokines and immunoglobulins in CTX immunosuppressed mice. Interestingly, CF improved all the mentioned parameters more effective than administration of SWP, FBTP or STA alone. In addition, CF was more effective to increase the levels of intestinal immune‐related gene expression than FBTP, SWP or STA alone in immunosuppressed mice, suggesting that CF exhibited excellent intestinal immune regulation function. CF also significantly improved cecal concentrations of short‐chain fatty acids of CTX‐treated mice. Furthermore, metabolomics analysis demonstrated that CF recovered the levels of 28 metabolites associated with the CTX treatment to the levels of normal mice. CONCLUSION: Conclusively, these findings suggested that CF as a functional food combination of SWP, FBTP and STA could promote the immune function against human diseases, which providing theoretical support for the co‐ingestion of SWP and functional sugars as a feasible strategy for improving the body immunity in the future. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Tetrabromobisphenol A (TBBPA) is a common environmental pollutant which has multi‐organ toxicity to mammals. Eucalyptol (EUC) has super antioxidant biological activity. However, in this experimental study, we probed into the mechanism of toxic of TBBPA exposure on Grass carp hepatocytes (L8824 cells) and the antagonistic impact of EUC on TBBPA. We treated L8824 cells with 8 μg/ml TBBPA and/or 20 μM EUC for 24 h in this test research. The experiment results suggested that TBBPA exposure induced elevated levels of reactive oxygen species (ROS), led to oxidative stress, decreased SOD and CAT activities, decreased GSH and T‐AOC contents, exacerbated MDA accumulation, activated ASK1/JNK signaling pathway, and further increased the contents of mitochondrial dependent apoptosis pathway related indicators (Cyt‐C, Bax, Caspase 9, Caspase 3), while Bcl‐2 expression decreased. In addition, TBBPA exposure induced increased expression of TNF‐α, IL‐6, IL‐1β, and decreased expression of IL‐2, IFN‐γ, Hepcidin, β‐defensin, LEAP2. The oxidative stress level, ASK1/JNK signal pathway expression level, apoptosis ratio and cellular immune function of cells exposed to EUC alone did not change significantly. Combined exposure of TBBPA and EUC significantly reduced the proportion of apoptosis and restored cellular immune function. Therefore, these results suggest that EUC can effectively antagonize TBBPA‐induced apoptosis and immune dysfunction of L8824 cells by regulating ROS/ASK1/JNK signaling pathway. [ABSTRACT FROM AUTHOR]

Sweet potato vine, the byproduct of sweet potato, has a high nutritional value. Silage is an effective solution for nutrient preservation. This article explored the effects of sweet potato vine silage (SPVS) supplementation on meat quality, antioxidant capacity and immune function in finishing pigs. One hundred and eighty finishing pigs (Berkshire × Licha Black) with a body weight of 74.54 ± 3.32 kg were randomly divided into three groups. The three groups were separately fed basal diet (Ctrl), Ctrl supplemented with 2.5% SPVS (LSPVS) or 5% SPVS (HSPVS) on a dry matter basis. Results showed that the eye muscle area in the LSPVS group was significantly increased. The carcass weight in the HSPVS was significantly reduced compared with Ctrl. For the meat quality, only cooking loss in both HSPVS and LSPVS was reduced while other indexes had no significant differences. For the antioxidant capacity, the hepatic level of glutathione (GSH) peroxidase (GSH‐PX) was significantly upregulated in LSPVS but downregulated in HSPVS. In the serum, HSPVS decreased GSH level and increased GSH‐PX level. HSPVS significantly reduced hepatic interleukin‐1β (IL‐1β) levels and LSPVS significantly reduced IL‐12 levels and increased IL‐8 and IL‐6 levels. Moreover, HSPVS and LSPVS promoted the secretion of immunoglobulin M (IgM) and IgG in the serum. Our data showed that low‐dose SPVS supplementation improved carcass traits and high‐dose SPVS supplementation increased immune function in finishing pigs, which provides a new alternative to improve animal health. [ABSTRACT FROM AUTHOR]

Daily light–dark cycles shape the circadian physiology and behaviour of nearly all organisms, with variation in circadian phenotypes having cascading effects on individual fitness, species interactions and species co‐evolution.Recent evidence that circadian rhythms in host immunity and metabolism are synchronised by the gut microbiota suggest that the circadian dynamics of gut microbes are a crucial component of their function. However, there remains little knowledge or understanding of the diurnal dynamics of gut microbiomes in natural populations or the consequences for host physiology and ecology.Here, we summarise the hallmarks of gut microbiota oscillations reported to date and the mechanisms by which they synchronise rhythms in host immunity and metabolism. We outline the consequences for diverse biological processes such as host pathogen susceptibility and seasonal switches in metabolism, and discuss how the breakdown of these circadian interactions, for example during senescence or because of light pollution, may affect wildlife infection risk and disease.We also provide practical guidelines for the measurement of microbial oscillations in wildlife, highlighting that whilst faecal samples of wild animals are rarely available over a 24‐h period, characterising even parts of the gut microbial cycle can be informative.An improved understanding of how gut microbial diurnal rhythms manifest in wildlife is essential to fully comprehend their role in shaping variation in host circadian phenotypes and the consequences for host physiology and ecology. Read the free Plain Language Summary for this article on the Journal blog. [ABSTRACT FROM AUTHOR]

Group A streptococci have evolved multiple strategies to evade human antibodies, making it challenging to create effective vaccines or antibody treatments. Here, we have generated antibodies derived from the memory B cells of an individual who had successfully cleared a group A streptococcal infection. The antibodies bind with high affinity in the central region of the surface‐bound M protein. Such antibodies are typically non‐opsonic. However, one antibody could effectively promote vital immune functions, including phagocytosis and in vivo protection. Remarkably, this antibody primarily interacts through a bivalent dual‐Fab cis mode, where the Fabs bind to two distinct epitopes in the M protein. The dual‐Fab cis‐binding phenomenon is conserved across different groups of M types. In contrast, other antibodies binding with normal single‐Fab mode to the same region cannot bypass the M protein's virulent effects. A broadly binding, protective monoclonal antibody could be a candidate for anti‐streptococcal therapy. Our findings highlight the concept of dual‐Fab cis binding as a means to access conserved, and normally non‐opsonic regions, regions for protective antibody targeting. Synopsis: Group A streptococci are experts at avoiding and disarming human antibodies with no available vaccines or antibody treatments. This study presents a novel interaction mechanism between antibodies and antigens that can induce protective immune function against group A streptococci. We have generated antibodies from human B cells against streptococcal M protein cross‐reactive across bacterial strains.One antibody can contact its target antigen at two sites in a cis‐bivalent manner, which we term dual‐Fab binding.Comparing antibodies that share epitopes but have single vs. dual‐Fab binding showed that dual‐Fab binding is associated with strongly enhanced immune function.Animal studies show that dual‐Fab antibodies can protect animals against streptococcal disease. [ABSTRACT FROM AUTHOR]

Probiotics have been increasingly investigated for their role in alleviating symptoms of ulcerative colitis (UC), but the specific mechanism involved remains unclear. We investigated the alleviating effect of Bifidobacterium animalis A6 (BAA6) in UC through a mouse dextran sulfate sodium (DSS) model. When treated with a high dose of BAA6 (1 × 1010 cfu/ml), it was found that colitis symptoms were significantly alleviated, and mucosal damages experienced obvious relief. Moreover, a high dose of BAA6 effectively upregulated free fatty acid receptors 2 and 3 (FFAR2 and FFAR3) expression and butyric acid metabolism specifically. Furthermore, the supplement of BAA6 significantly suppressed pro‐inflammatory cytokines levels (interleukin‐13) and the expression of pore‐forming protein claudin‐2. The upstream regulatory genes of claudin‐2, such as STAT6, GATA4, Cdx2, were also significantly inhibited by BAA6. Collectively, this study concludes that BAA6 attenuated DSS‐induced colitis by increasing the levels of intestinal butyric acid, activating the butyric acid‐FFAR pathway, suppressing excessive proinflammatory response, and protecting the function of the colon epithelial barrier. [ABSTRACT FROM AUTHOR]

An 80‐day feeding trial was performed to investigate the effect of dietary β‐sitosterol supplementation on intestinal immune function in large yellow croaker. 540 fish (initial average weight: 189.74 ± 0.31 g) were fed six diets containing graded levels of β‐sitosterol (0.0%, 0.5%, 1.0%, 1.5%, 2.0% and 2.5%) and then challenged with Aeromonas hydrophila for 10 days. Results demonstrated that dietary β‐sitosterol (1) improved growth performance, attenuated enteritis morbidity and intestinal histopathological lesions; (2) increased lysozyme and acid phosphatase activities, complement 3 and complement 4 contents as well as IgM contents (not in the proximal intestine [PI]) and up‐regulated LEAP‐2C (rather than LEAP‐2A) and hepcidin mRNA expressions in the intestine; (3) down‐regulated pro‐inflammatory cytokines IL‐1β (not in PI), IL‐2, IL‐6, IL‐8, IFN‐γ and IFITM mRNA expressions partly associating with NF‐κB signalling and up‐regulated anti‐inflammatory cytokines IL‐4/13A (not IL‐4/13B), IL‐11 and TGF‐β mRNA expressions partly associating with TOR signalling in the intestine. Finally, based on percentage weight gain, enteritis morbidity and lysozyme activities in three intestinal segments, the optimal dietary β‐sitosterol supplementation levels were estimated to be 1.44%, 2.03%, 2.11%, 1.94% and 1.69% diets respectively. In summary, the optimal dietary β‐sitosterol supplementation improved immune function in the intestine of large yellow croaker. [ABSTRACT FROM AUTHOR]

The effects of L‐carnitine (LC) and dietary lipid on the growth and health of farmed fish are still conflicting. This study aimed to explore the effects of LC supplementation and dietary fish oil replacement by corn oil on growth performance, antioxidant, immune function and histomorphology of Rhynchocypris Lagowskii. Six diets were evaluated as follows: dietary fish oil as 50% and 100% replacement by corn oil, and differing in LC supplementation (0 and 400 mg/kg), were tested in R. Lagowskii for 8 weeks. The highest weight gain rate, specific growth rate and feed efficiency were observed in mix oil diets with LC. The diet with LC significantly increased the total antioxidant capacity level, total superoxide dismutase, alkaline phosphatase, lysozyme activities and immunoglobulin M, complement levels in liver and intestine compared with corn oil diet (p < 0.05). Moreover, the diet with LC significantly up‐regulated the nuclear factor E2‐related factor 2 (p < 0.05), and significantly down‐regulated the interleukin‐1‐beta and tumour necrosis factor‐alpha expression in liver and intestine compared with corn oil diet (p < 0.05). In conclusion, LC supplementation improved the weakening of growth performance, antioxidant capacity, immune function and tissue health caused by R. lagowskii intake of corn oil diets. [ABSTRACT FROM AUTHOR]

Almost every living organism on earth is exposed to a fluctuating environment, for example, light:dark cycles, food availability and seasonal photoperiods. Most species have therefore evolved internal timing mechanisms allowing them to anticipate these rhythmic environmental changes, obtaining a survival advantage. Circadian (24 h) rhythms, in particular, regulate multiple aspects of physiology, including sleep/wake activity, feeding rhythms and immune function. Recent studies have identified circadian rhythms in symptoms of parasite infections, rhythms in parasite schizogony and evidence that certain parasites can manipulate host rhythms. Furthermore, efficacy of anti‐parasite medications can also be modulated by timing of drug administration. Understanding the interactions between host rhythms, parasite rhythms and disease severity is crucial to fully understand how to combat infections and reduce pathology. The aim of this review is, therefore, to provide an introduction to the field of biological rhythms, give a brief history of chronobiology research and discuss the relevance of biological rhythms to parasite immunology. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS CoV‐2) is a lethal virus that causes COVID‐19 (Coronavirus disease 2019), the respiratory illness that has caused the COVID‐19 pandemic. Even though multiple pharmacological trials are ongoing, there is no proof that any treatment will effectively cure or prevent COVID‐19. Currently, COVID‐19‐infected patients are being managed with non‐specific medications to suppress the symptoms and other associated co‐morbidities. Nitric oxide is a bio‐signaling molecule that has been shown to be effective for treating several viral infections in humans. Household Natural foods rich in nitrites and nitrates (NO donors) have been scientifically proven to have therapeutic benefits against immune‐related respiratory tract infections. It was understood that NO could inhibit the early stage of SARS CoV‐2 invasion into the human cell. Fruits and vegetables containing nitrites and nitrates have been revised and are now thought to be potential anti‐CoV agents for effective control of other associated systemic disorders. The purpose of this review is to highlight some key facts about the treatment and prevention of COVID‐19 infection with foods rich in nitric oxide and its donors. Practical applications: Improving the body's immune system is the early step to be considered as a preventive measure to stop the spreading of COVID‐19 infection. Emerging research continues to mount that dietary nitrates/nitrites from plant foods are being healthy as well as keep us away from infectious diseases. They are now incorporated into low‐risk adjuvant therapy for various infections and systemic disorders. This concept portrays the regular consuming foods such as fruits and vegetables that are rich in nitric oxide which have the potential to promote health, improve general well‐being, and reduce the risk associated with the highly contagious diseases. Hence, we recommend adding nitrates and nitrites‐containing food to the regular diet to improve the self‐immunity as well as to fight against COVID‐19 disease. [ABSTRACT FROM AUTHOR]

Phagocytosis is a fundamental immune function against foreign microorganisms and abnormal cells, and it is also a bridge between innate and adaptive immunity. Blood as the direct living environment of various immune cells is a crucial site for phagocytosis. In this review, we firstly summarized the morphological structure and cytochemical characteristics of teleost peripheral blood cells, divided them into erythrocytes, leucocytes and thrombocytes, and then systematically elaborated the immune functions of phagocytic blood cells including professional and non‐professional phagocytes. The professional phagocytes consist of monocytes/macrophages and neutrophils. Monocytes/macrophages activate phagocytosis to ingest pathogens, and destroy them through respiratory burst and nitric oxide response to generate antigens, and then antigens are presented to adaptive immune cells. Neutrophils are recruited to inflammatory sites and exert phagocytosis, which is accompanied by degranulation and the production of neutrophil extracellular traps to kill pathogens. Non‐professional phagocytes including thrombocytes, B cells and erythrocytes are indispensable to exercise the phagocytosis, in addition to their main functions in the immune system. Thrombocytes participate in innate immunity and adaptive immunity. B cells carry out antigen presentation and immunoglobulin secretion in adaptive immunity. Erythrocytes perform immune regulation and infection resistance. In general, professional phagocytes play a primary role in phagocytosis and pathogen treatment, whereas non‐professional phagocytes play auxiliary role in phagocytosis and perform their unique immune functions. The functions of these two types of phagocytes jointly constitute the basis of the immune system. This review provides insights into the overall roles of phagocytic blood cells in the teleost immune system. [ABSTRACT FROM AUTHOR]

Aquaculture in North America is currently dominated by Atlantic salmon, but there has been an increasing interest in the production of species native to the Pacific coast. Chinook salmon is relatively new to production; therefore, the selection of appropriate stocks is critical. Often genes from wild populations are incorporated into farmed stocks to avoid performance decreases associated with inbreeding. The present study focuses on assessing the immunological performance of one inbred stock and seven outbred/hybrid crosses after challenge with the marine pathogen, Vibrio anguillarum. Throughout exposure challenge to both pathogen and sterile PBS, significant differences in mortality were observed between crosses. Fish were also assessed for major histocompatibility complex (MHC) class II β1 genotype, and although particular alleles did not confer resistance, crosses with better survival had more individuals presenting a heterozygous genotype. The stress induced during infection resulted in several individuals presenting signs of Bacterial Kidney Disease (Renibacterium salmoninarum) indicating that chronic co‐infection may have contributed to susceptibility. When spleen samples from the highest and lowest performing hybrid crosses were assessed for cytokine and respiratory burst gene expression throughout bacterial challenge, high surviving crosses presented lower expression of inflammatory cytokine transcripts (IL‐1β, IL‐6 and TNFα) when compared to low performing crosses. Interestingly, microsatellite analysis revealed no significant differences in inbreeding coefficient or allelic richness between crosses despite observed variation in immune performance. Understanding the impact of outbreeding on the immune function of farmed, and often inbred, Chinook salmon could aid in future development of high‐quality aquaculture stocks for this species. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the effects of methionine hydroxyl analog chelated microminerals (MHA-M) replacing inorganic microminerals (ITMs) on the growth performance, fecal microminerals concentrations, immune function, and antioxidant status in growing-finishing pigs; 253 pigs (average 33.68 kg body weight) were randomly assigned to six treatments with six replicates each treatment: (1) ITM: a basal diet with Cu, Fe, Mn, and Zn from sulfates providing 20, 100, 40, and 60 mg/kg; (2–6): 1/5MHA-M, 2/5MHA-M, 3/5MHA-M, 4/5MHA-M, and MHA-M was replaced with 20%, 40%, 60%, 80%, and 100% MHA-M. Results showed that the average daily gain (ADG) in the 1/5MHA-M and 2/5MHA-M was greater than other groups in the whole period. Fecal Cu, Fe, Mn, and Zn concentrations had decreased as the intake of trace minerals decreases. The ITM group decreased the fecal Zn concentration on Days 35, 70, and 91, and Fe concentration on Day 70, and increased the Mn concentration on Day 70 compared with MHA-M group. Pigs fed 1/5MHA-M, 2/5MHA-M, and MHA-M had a higher immune function and antioxidant status in serum compared with ITM, 3/5MHA-M, and 4/5MHA-M on Day 35. In conclusion, treatment with 1/5MHA-M and 2/5MHA-M could reduce the excretion of fecal microminerals and improve the immune function and antioxidant capacity compared with the ITM group [ABSTRACT FROM AUTHOR]

Amphibian populations are decreasing worldwide, and pollution is a contributing factor. Polychlorinated biphenyls (PCBs) are a class of persistent organic pollutants known to exert immunotoxicity. To assess impacts of PCBs on frogs, we exposed Lithobates pipiens tadpoles to a diet of PCB‐126 (0–5 ng PCB‐126/g wet food) through metamorphic climax. Postmetamorphic frogs were immunized with keyhole limpet hemocyanin (KLH); then production of KLH‐specific IgY, as well as total IgY and IgM, was measured (Trial I). A second larval study (0 and 7.3 ng PCB‐126/g wet food) was performed to investigate whether PCB altered antigenic responses in prometamorphic tadpoles (Gosner Stage 36–39), and to measure the innate immune response of postmetamorphic frogs (Trial II). After larval PCB‐126 exposure, both KLH‐specific IgY levels and complement activity were reduced. Because postmetamorphic frogs carried a body burden of PCB‐126 (2.4 ng/g or less), we wanted to determine whether the effect on immune response was due to larval exposure or to the resulting body burden as frogs. To test this, we reared tadpoles under control conditions (no PCB), and limited PCB exposure to postmetamorphosis only by injecting 2‐week‐old frogs with 10 ng PCB‐126/g (Trial III). The resulting body burden (3.4 ng/g) was similar to that of frogs in Trial I, but we no longer detected suppression of KLH‐specific IgY or hemolytic activity. These results suggest life‐stage–specific immune responses; however, because we administered PCB‐126 differently between trials, it is premature to conclude that these differences are intrinsically life stage dependent, and further study is warranted. Regardless, our study demonstrated a long‐lasting effect of larval PCB‐126 exposure that persisted through metamorphosis and suppressed frog immunity. Environ Toxicol Chem 2022;41:81–94. © 2021 SETAC [ABSTRACT FROM AUTHOR]

Circulating concentrations of canonically pro‐ and anti‐inflammatory cytokines are commonly measured when evaluating the anti‐inflammatory effects of exercise. An important caveat to interpreting systemic cytokine concentrations as evidence for the anti‐inflammatory effects of exercise is the observed dissociation between circulating cytokine concentrations and cytokine function at the tissue/cellular level. The dichotomization of cytokines as pro‐ or anti‐inflammatory also overlooks the context dependence of cytokine function, which can vary depending on the physiological state being studied, the cytokine's cellular source/target, and magnitude of cytokine responses. We re‐evaluate our current understanding of anti‐inflammatory cytokine responses to exercise by highlighting nuances surrounding the interpretation of altered systemic cytokine concentrations as evidence for changes in inflammatory processes occurring at the tissue/cellular level. We highlight the lesser known pro‐inflammatory and immunostimulatory actions of the prototypical anti‐inflammatory cytokine, interleukin (IL)‐10, including the potentiation of interferon gamma production during endotoxaemia, CD8+ T cell activation in tumour bearing rodents and cancer patients in vivo, and CD8+ T lymphocyte and natural killer cell activation in vitro. IL‐10's more well‐established anti‐inflammatory actions can also be blunted following exercise training and under chronic inflammatory states such as type 2 diabetes (T2D) independently of circulating IL‐10 concentrations. The resistance to IL‐10's anti‐inflammatory action in T2D coincides with blunted STAT3 phosphorylation and can be restored with small‐molecule activators of IL‐10 signalling, highlighting potential therapeutic avenues for restoring IL‐10 action. We posit that inferences based on altered circulating cytokine concentrations alone can miss important functional changes in cytokine action occurring at the tissue/cellular level. [ABSTRACT FROM AUTHOR]

The present study was conducted to evaluate the utilization of both pelleted feed (PF) and extruded feed (EF) by blunt snout bream Megalobrama amblycephala based on growth performance, stress responses, innate immunity and disease resistance. Both the PF and EF were prepared with the same formula. Fish were divided randomly into 2 groups, including one fed the PF continuously and one offered the EF continuously. The whole feeding trial lasted 8 weeks, after which fish were subjected to Aeromonas hydrophila infection. The results showed that the feed intake, feed conversion ratio, hepatic total superoxide dismutase activity and glutathione content, plasma complement 3 and complement 4 levels as well as myeloperoxidase activity of the EF group were all significantly lower than those of the PF group, while the opposite was true for the condition factor, the viscera index, the abdominal fat percentage, nitrogen and energy retention, hepatic malondialdehyde content, plasma levels of cortisol, glucose, lactate, total protein and globulin as well as the activities of plasma alanine aminotransferase and aspartate aminotransferase. In addition, the EF group also obtained relatively low activities of hepatic glutathione peroxidase and plasma acid phosphatase as well as high cumulative mortality rates at 24–96 h after Aeromonas hydrophila challenge. Furthermore, the feed cost of culturing this species with EF is lower than that with PF. These findings indicated that compared with PF, EF could increase the feed utilization and economic benefits of blunt snout bream, but reduce its anti‐stress ability, non‐specific immunity, A. hydrophila resistance and feed cost. [ABSTRACT FROM AUTHOR]

The present study investigated the effects of Bacillus coagulans and yeast hydrolysate supplementation on growth performance, immune response and intestinal barrier function of weaned piglets. Twenty‐four weaned piglets with an average body weight (BW) of 6.89 ± 0.15 kg were divided into four diets for 28 days. The treatments were basal diet (control), basal diet supplemented with antibiotic (20 mg/kg colistin sulphate and 40 mg/kg bacitracin zinc, AT), probiotics (400 mg/kg Bacillus coagulans ≥5 × 109 CFU/g, BC) or yeast hydrolysate (5000 mg/kg yeast hydrolysate, YH). Average daily gain (ADG) and average daily feed intake (ADFI) were improved by AT and YH diets (p < 0.05), while BC diet only increased ADG (p < 0.05). The complement 3 (C3), lysozyme (LZM) and tumour necrosis factor‐α (TNF‐α) concentrations in serum were increased in BC diet (p < 0.05). Feeding AT and YH caused the increase of jejunal villus height (p < 0.05), and a higher ratio of villus height/crypt depth was observed in AT, BC and YH groups (p < 0.05). The mRNA expression of zonula occludens‐1 (ZO‐1) in jejunal mucosa was up‐regulated by AT, BC and YH diets (p < 0.05). Dietary AT, BC or YH inclusion decreased the interleukin‐1β (IL‐1β) concentration and TNF‐α mRNA expression (p < 0.05), and YH supplementation even down‐regulated toll‐like receptor 4 (TLR4) and CD14 expressions (p < 0.05). In summary, the dietary administration of BC or YH both improves growth performance through promoting the intestinal barrier function, indicating both of them can serve as potential alternatives to antibiotics growth promoters for the piglet production. [ABSTRACT FROM AUTHOR]

New Findings: What is the central question of this study?Is lymphocyte DNA methylation differentially modulated by resistance training and aerobic exercise in older women?What is the main finding and its importance?The practice of resistance training led to an increased global DNA methylation in lymphocytes. The exercise‐induced increase of inflammatory genes methylation may be associated with immune function impairment during ageing. Ageing‐induced increase in inflammatory gene expression through a reduction in DNA methylation might contribute to chronic diseases. Regular physical exercise practices, in turn, are associated with a decrease in the incidence of inflammatory diseases. We herein evaluated the effects of three exercise modalities on lymphocyte global and gene‐specific (interferon γ (IFN‐γ) and interleukin 17A (IL‐17A) DNA methylation in aged women (68 ± 7.5 years). This cross‐sectional study included 86 women, divided into four groups according to the physical exercise practice: 20 were practicing resistance training (RT); 24 were practicing water aerobics exercise (W); 22 were practicing water aerobics and resistance exercise (RWT), and 20 did not practice any physical exercise (CON). We evaluated volunteer functional capability using the Timed Up and Go (TUG) test, global lymphocyte DNA methylation by enzyme‐linked immunosorbent assay, IFN‐γ and IL‐17A methylation by qPCR and CD4+IFN‐γ+ and CD4+IL‐17+ cell percentage by flow cytometry. The three physically exercised groups performed functional capability tests in a shorter period and showed a higher global lymphocyte DNA methylation and methylated CpGs of IL‐17A and IFN‐γ promoter regions than the control group. The practice of resistance training (RT and RWT groups) lead to high global DNA methylation. The combination of resistance training and aerobic exercise led to the increase of lymphocyte IL‐17A and IFN‐γ gene methylation induced by each separately. However, the percentage of IFN‐γ+ and IL‐17+ cells was lower only in the RT group. The exercise‐induced increase of inflammatory‐gene methylation may be associated with gene expression changes and immune function impairment during ageing. [ABSTRACT FROM AUTHOR]

A novel polysaccharide was extracted from Sipunculus nudus (SNP). The molecular weight (MW) of SNP was determined to be 9223 Da by high‐performance gel permeation chromatography analyses, and the structure of the SNP repeat units was determined to be →3,4‐β‐D‐GlcpNAC (1→ and →4) ‐α‐D‐Glcp (1→ in the ratio of 15:1; →2) ‐α ‐D‐Galp ‐ (1→ as a side chain; and β‐D‐Galp‐(1→ and α‐ D‐Glcp ‐ (1→ as end groups by GC‐MS analysis and NMR assays. The effect of SNP on hepatoma HepG2‐bearing mice was analysed to verify its potential in the clinical treatment of liver cancer. A total of 90 male athymic nu/nu mice were divided into therapeutic and preventive groups and fed with different amounts of SNP. The antitumour effect of SNP on HepG2‐bearing mice and mechanism of such were studied by analysing the tumour size, spleen index, thymus index, immune factors in the blood, tumour apoptosis factors, etc. The results suggest that SNP not only increased the index of immune organs in the body, but also enhanced the secretion of immune factors, including interleukin‐2, interferon gamma and tumour necrosis factor‐alpha in the serum. SNP induced the apoptosis of tumour cells via the mitochondrial apoptosis pathway, which upregulated caspase‐3, caspase‐8, caspase‐9 and BCL2‐associated X, but downregulated B‐cell lymphoma‐2 and vascular endothelial growth factor protein expression. In conclusion, SNP inhibited tumour growth by enhancing immune function and inducing tumour cell apoptosis in HepG2‐bearing mice. Therefore, SNP may be further investigated as a promising candidate for future antitumour drugs. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the effects of adding Pennisetum purpureum (P. purpureum, also known as Napier grass or elephant grass) to the diets of late gestation on the antioxidant indexes, immune indexes and faecal microbiota of sows. At the 90 days of gestation, 300 healthy sows were randomly divided into three groups, and they received the basic commercial diet or added 5% P. purpureum and 10% P. purpureum, respectively. The experiment started from 90 days of gestation to parturition. The results showed that the total antioxidant capacity, immunoglobulins and serum equol concentrations of sows on 100 days of gestation and at parturition increased linearly (p <.05) with the increase of the content of P. purpureum in the gestation diet. The 5% P. purpureum increased the relative abundance of Bacteroidetes (p =.027) and Actinobacteria (p <.001) at phylum level, Coriobacteriaceae (p <.001) at family level and Prevotellaceae_UCG_001 (p =.004) at genus level, and decreased the relative abundance of Escherichia_Shigella (p <.001) at genus level. In summary, this study shows that the additive of P. purpureum can increase the concentration of serum equol, improve the antioxidant capacity and immune function of sow in late gestation. In addition, the additive of 5% P. purpureum in the diet might change the composition of intestinal microbiota of sows, particularly the relative abundance of Coriobacteriaceae (p <.001) increased. [ABSTRACT FROM AUTHOR]

Persistent contaminants are ubiquitous in our water and soil, and thus chronic exposure to environmentally relevant levels of these contaminants may pose a risk to humans and wildlife. Two species of small mammals (deer mouse, Peromyscus maniculatus and cotton rat, Sigmodon hispidus) were collected from historically dichlorodiphenyltrichloroethane (DDT)‐contaminated and reference areas at the Redstone Arsenal (Huntsville, AL, USA), a US Environmental Protection Agency (USEPA)‐designated Superfund site. Soil samples taken concurrently with mammal collection from the DDT abatement site exhibited DDT and dichlorodiphenyldichloroethylene (DDE) levels >1 ppm (USEPA total threshold limit concentration for DDT and DDE <1 ppm), whereas soil samples from the reference area had undetectable levels. Liver samples from individuals of both species collected in the contaminated areas also had significantly elevated DDT/DDE levels, with P. maniculatus averaging an approximately 20× greater load than that documented for S. hispidus. Both rodent species collected from the contaminated site had significantly lower total leukocyte counts and total differential blood cell counts (p = 0.01 and p = 0.04, respectively) than those collected from the nearby (~7000‐m) reference site. Cellular stress indices also trended higher in both species, suggesting a potential for chronic exposure to DDT to act as a mediator of oxidative damage. The present study provides support to the idea that environmental exposure to low levels of contaminants can cause physiological consequences that may influence immune responsiveness and initiate cellular stress in resident mammals. Environ Toxicol Chem 2021;40:1619–1629. © 2021 SETAC [ABSTRACT FROM AUTHOR]

Aim: Angiotensin‐converting enzyme 2 (ACE 2) is the binding domain for severe acute respiratory syndrome coronavirus (SARS‐CoV) and SARSCoV‐2. Some antihypertensive drugs affect ACE2 expression or activity (ACE inhibitors and angiotensin II receptor blockers [ARBs]), suggesting use of other hypertensives might be preferable, such as calcium channel blockers (CCBs). Given the limited evidence, the International Society of Hypertension does not support such a policy. Methods: We used a Mendelian randomization study to obtain unconfounded associations of antihypertensives, instrumented by published genetic variants in genes regulating target proteins of these drugs, with immune (lymphocyte and neutrophil percentage) and inflammatory (tumour necrosis factor alpha [TNF‐α]) markers in the largest available genome‐wide association studies. Results: Genetically predicted effects of ACE inhibitors increased lymphocyte percentage (0.78, 95% confidence interval [CI] 0.35, 1.22), decreased neutrophil percentage (−0.64, 95% CI −1.09, −0.20) and possibly lowered TNF‐α (−4.92, 95% CI −8.50, −1.33). CCBs showed a similar pattern for immune function (lymphocyte percentage 0.21, 95% CI 0.05 to 0.36; neutrophil percentage −0.23, 95% CI −0.39 to −0.08) but had no effect on TNF‐α, as did potassium‐sparing diuretics and aldosterone antagonists, and vasodilator antihypertensives. ARBs and other classes of hypertensives had no effect on immune function or TNF‐α. Conclusion: Varying effects of different classes of antihypertensives on immune and inflammatory markers do not suggest antihypertensive use based on their role in ACE2 expression, but instead suggest investigation of the role of antihypertensives in immune function and inflammation might reveal important information that could optimize their use in SARSCoV‐2. [ABSTRACT FROM AUTHOR]

Objectives: Flow cytometry is a powerful tool for investigating immune function, allowing for the quantification of leukocytes by subtype. Yet it has not been used extensively for field work due to perishable reagents and the need for immediate analysis of samples. To make flow cytometry more accessible, we devise and evaluate a field protocol for freezing capillary blood. Materials and Methods: We collected finger prick blood samples from 110 volunteers, age 18 to 42. Blood samples were analyzed immediately for 18 cell surface markers. Aliquots of whole blood were frozen in the vapor phase of a liquid nitrogen tank with 10% dimethyl sulfoxide in medium. Samples were analyzed on a Guava EasyCyte HT flow cytometer after 2, 4, or 14 weeks. Results: Major lymphocyte fractions in frozen samples were correlated with fresh values (T‐cells: r = 0.82; Natural Killer [NK] cells: r = 0.64; CD4: r = 0.67; CD8: r = 0.82; Naïve CD4: r = 0.73, Naïve CD8: r = 0.71; B‐cells: r = 0.73; all p < 0.001), and mean values were similar to those from fresh samples. However, correlations for smaller subsets of CD4 and B cells were generally poor. Some differences resulted from changes in non‐specific binding for some antibody‐conjugate pairs. Cryopreservation also resulted in a reduction in granulocytes more than lymphocytes. Discussion Our results suggest that antibody/fluorochrome combinations should be validated before use on frozen samples, and that functional changes in cells may affect some cell markers. However, this simple freezing protocol utilizing finger pricks, whole blood, and a liquid nitrogen shipping tank is viable for obtaining samples for flow cytometry under field conditions. [ABSTRACT FROM AUTHOR]

There may be immunologic alternations during Tourette syndrome (TS) development. This study aimed to determine the immune function changes in different aspects (spleen or thymus index, plasma cytokines, and T cell) in an 3,3′‐iminodipropionitrile (IDPN)‐induced rat model of TS. Male Sprague‐Dawley rats were assigned to control and TS groups. The control group received intraperitoneal infections of normal saline (5 ml kg−1 day−1), and the TS rats were injected with IDPN (150 mg kg−1 day−1). The spleen and thymus indices were calculated. The expression of anti‐inflammatory cytokines and inflammatory cytokines TNF‐α, in peripheral blood were measured by ELISA and Western blotting. The proportion of CD3+, CD4+, CD8+, Treg, Th1, and Th2 cells were determined by fluorescence‐activated cell sorting analysis. After 1 week of IDPN treatment, TS rats had decreased spleen and thymus weights versus control. The plasma levels of IL‐4, IL‐10, IL‐12, IFN‐γ, and TNF‐α were significantly increased, while no significant difference in TGF‐β was found. Flow cytometry analysis demonstrated that TS rats had significantly reduced CD3+ and CD4+ cells in spleen, without any change in the proportion of CD8+ cells. Furthermore, the ratio of Treg cells (CD4+/CD25+/FoxP3+) was decreased in TS rats; simultaneously, Th1 cells (CD4+/IFN‐γ+) and Th2 cells (CD4+/IL4+) were dramatically increased. Together, IDPN can trigger immune dysfunction through impairment of matured Th cells, in particular for the Treg subset. [ABSTRACT FROM AUTHOR]

The influence of surgery and anesthesia on immune function during the perioperative period should not be neglected. In this study, we evaluated the effects of oxycodone combined with flurbiprofen axetil on postoperative analgesia and immune function in patients undergoing radical resection of colorectal cancer (CRC). One hundred and thirty‐three were randomized into the oxycodone combined with flurbiprofen axetil (OF) group or the sufentanil combined with flurbiprofen axetil (SF) group. Patients in the OF group were prescribed oxycodone hydrochloride 0.1 mg/kg combined with flurbiprofen axetil 3 mg/kg for postoperative analgesia, whereas the SF group received sufentanil 0.1 μg/kg combined with flurbiprofen axetil 3 mg/kg. The primary outcome was visual analog scale (VAS) score. Secondary outcomes included the quantities of CD4+, CD8+, and natural killer (NK) T cells, tumor necrosis factor (TNF)‐α level, and interleukin (IL)‐6 in peripheral blood, the consumption of analgesics, and the incidence of adverse reactions, and so forth. The VAS scores at rest were similar in both group. However, the VAS scores at cough in the OF group at 8, 12, and 24 hours postsurgery were lower than those in the SF group. Compared with the SF group, the count of CD4+ T cells and ratio of CD4+/CD8+ were higher in the OF group at 12, 24, 48, and 72 hours postsurgery, although the count of CD8+ and NK T cells was higher than that in the SF group at 48 and 72 hours postsurgery. In addition, the serum level of TNF‐α and IL‐6 at 12, 24, 48, and 72 hours postsurgery in the OF group was lower than that in the SF group. In addition, the incidence of postoperative nausea, postoperative vomiting, and pruritus was lower, the time to first flatus and bowel movement was earlier in the OF group. Oxycodone combined with flurbiprofen axetil applied for patient‐controlled intravenous analgesia could effectively reduce pain intensity, particularly for visceral pain, and help to reverse the status of immunosuppression during radical resection of CRC. [ABSTRACT FROM AUTHOR]

Objective: Age‐associated decreases in immune functions are precipitated by a variety of mechanisms and affect nearly every immune cell subset. In myeloid cells, aging reduces numbers of phagocytes and impairs their functional abilities, including antigen presentation, phagocytosis, and bacterial clearance. Recently, we described an aging effect on several functions in monocytes, including impaired mitochondrial function and reduced inflammatory cytokine gene expression during stimulation with lipopolysaccharide. We hypothesized that circulating factors altered by the aging process underly these changes. Growth differentiation factor‐15 (GDF‐15) is a distant member of the transforming growth factor‐β superfamily that has known anti‐inflammatory effects in macrophages and has been shown to be highly differentially expressed during aging. Methods: We used biobanked plasma samples to assay circulating GDF‐15 levels in subjects from our previous studies and examined correlations between GDF‐15 and monocyte function. Results: Monocyte interleukin‐6 production due to lipopolysaccharide stimulation was negatively correlated to plasma GDF‐15. Additionally, GDF‐15 was positively correlated to circulating CD16 + monocyte proportions and negatively correlated to monocyte mitochondrial respiratory capacity. Conclusions: These results suggest that GDF‐15 is a potential circulating factor affecting a variety of monocyte functions and promoting monocyte immunosenescence and thus may be an attractive candidate for therapeutic intervention to ameliorate this. [ABSTRACT FROM AUTHOR]

Many measures of immune function used in ecoimmunological studies were optimized for endotherms and may not adequately characterize immunocompetence in ectothermic species. Lymphocytes are interpreted as functioning in adaptive immunity despite evidence that large proportions of these cells have innate immune functions, including phagocytosis, in ectotherms.We modified previously published protocols to remove many barriers that inhibited the wide application of assays to quantify phagocytic activity in lymphocytes. These barriers included the use of species‐specific reagents, high cost and incompatibility with field work. We statistically compared published methods to our simplified technique using blood samples collected from tortoises.We show the efficacy of the new technique and offer an outline for optimizing these methods for different species and to address a wide variety of ecoimmunological questions.A full understanding of immune function in ectothermic vertebrates is needed to comprehend complex epidemiological patterns. As our assay disentangles the relationship between effector cells (lymphocytes) and their function (phagocytosis), these methods provide a foundation for more thorough analyses of ecoimmunological patterns. [ABSTRACT FROM AUTHOR]