Iodine is an essential micronutrient required for coordinating thyroid hormone synthesis, growth, neurodevelopment, metabolism, and immune function across humans and domesticated mammals. Molecular iodine can act as an antioxidant, anti-inflammatory, and anti-proliferative agent in several tissues, but these mechanistic effects require confirmation in well-designed human studies. Recommended intakes fall within a narrow optimal range, reflecting a U-shaped response curve in which adequate intake supports systemic homeostasis, while both deficient and excessive intakes can impact immune function. Chronic deficiency impairs neurodevelopment and reproductive performance and weakens the host microbial defences, while sustained excess promotes oxidative stress, alters cytokine profiles, and in genetically susceptible individuals, increases the risk of subclinical or overt thyroid dysfunction and autoimmune thyroid disease. This review summarizes iodine nutrikinetics, dose-dependent outcomes and susceptibility in humans and domesticated mammalian species, emphasizing the importance of maintaining appropriate iodine status to support immunocompetence while minimizing adverse effects.

There are currently knowledge gaps regarding the development of the bovine B cell repertoire especially for cells expressing B cell receptors with heavy chain ultralong complementarity determining region 3 (CDR3). The objective of this study was to assess percentages of B cells with ultralong CDR3s, and immunoglobulin heavy chain gene usage in Holstein calves from birth to 10 mo of age. Blood was collected from 7 heifer calves on the following days of life: 0 (prior to ingestion of colostrum), 2 (after colostrum ingestion), 42, 56, 90, and 285. IgM+ and IgG+ B cells were collected using magnetic-bead separation. RNA was extracted, cDNA was produced, and IgM and IgG sequences were amplified using polymerase chain reactions. Amplicons were sequenced using long-read Oxford Nanopore sequencing on R10.4 flow cells. Differences in the percentages of B cells with ultralong CDR3s were assessed using non-parametric Wilcoxon signed-rank tests. The mean percentage of productive IgM ultralong CDR3 sequences at birth was 3.27%, which decreased by day 42 and remained low until there was a significant increase between day 90 and ∼day 285 (5.68% ± 1.51 standard error of the mean, P = 0.03). The mean percentage of productive IgG ultralong CDR3 sequences was low at birth (0.89%) and remained low until there was a significant increase between day 90 and ∼day 285 (6.86% ± 0.99, P = 0.03). These increases in the percentages of sequences with ultralong CDR3 may be indicative of increased antigenic exposure and concurrent maturation of immune functionality.

Lipopolysaccharide (LPS) endotoxin is a well-characterized microbe-associated molecular pattern (MAMP) that forms the outer membrane of both pathogenic and commensal Gram-negative bacteria. It plays a crucial role in triggering inflammatory disorders such as mastitis, acidosis, and septicemia. In heifers, an LPS challenge induces a dynamic stress response, marked by elevated cortisol levels, increased body temperature, and altered immune function. Research indicates that LPS administration leads to a significant rise in cortisol post-challenge. Building on this understanding, the present study aimed to estimate genetic parameters for serum cortisol response to LPS challenge in Holstein heifers and its linear associations with production, health, reproduction, and conformation traits. Additionally, a genome-wide association study (GWAS) was conducted to identify genetic regions associated with cortisol response. A total of 252 animals were evaluated for cortisol response, with correlations estimated between cortisol levels and 55 genomic breeding values for key traits. Genetic parameters and heritability for cortisol response were estimated using Residual Maximum Likelihood (REML) in the Blupf90+ v 2.57 software. Single-Step GWAS (ssGWAS) employing a 10-SNP window approach and 42,123 SNP markers was performed to identify genomic regions that explained at least 0.5% of additive genetic variance. Finally, candidate genes and QTLs located 50 kb up and downstream of those windows were identified. The cortisol response showed significant but weak linear associations with cystic ovaries, body maintenance requirements, lactation persistency, milk yield, and protein yield (p-value ≤ 0.05) and showed suggestive weak linear associations with udder texture, clinical ketosis, heel horn erosion, and milking speed (p-value ≤ 0.15). Cortisol response showed significant additive genetic variance, along with moderate heritability of 0.26 (±0.19). A total of 34 windows explained at least 0.5% of additive genetic variance, and 75 QTLs and 11 candidate genes, comprising the genes CCL20, DAW1, CSMD2, HMGB4, B3GAT2, PARD3, bta-mir-2285aw, CFH, CDH2, ENSBTAG00000052242, and ENSBTAG00000050498, were identified. The functional enrichment analysis allowed us to infer two instances where these gene products could interfere with cortisol production: the first instance is related to the complement system, and the second one is related to the EMT (Epithelium–Mesenchymal Transition) and pituitary gland formation. Among the QTLs, 13 were enriched in the dataset, corresponding to traits related to milk (potassium content), the exterior (udder traits, teat placement, foot angle, rear leg placement, and feet and leg conformation), production (length of productive life, net merit, and type), and reproduction (stillbirth and calving ease). In summary, the cortisol response to LPS challenge in Holstein heifers seems to be moderately heritable and has weak but significant linear associations with important production and health traits. Several candidate genes identified could perform important roles, in at least two ways, for cortisol production, and QTLs were identified close to regions of the genome that explained a significant amount of additive genetic variance for cortisol response. Therefore, further investigations are warranted to validate these findings with a larger dataset.

Abstract Selenium (Se) is an essential mineral for animal health. Due to widespread soil Se deficiency in global regions, selenium must be supplemented in sheep diets to prevent harmful conditions such as white muscle disease (WMD). Previous research has also demonstrated the beneficial immunomodulatory properties of Se in improving antibody production and reducing inflammation. Beyond its role in disease prevention and immunomodulation, Se functions as a potent antioxidant, promotes thyroid hormone metabolism, and improves reproductive outcomes. Strategies for improving animal Se status can include adding Se to mineral premixes, salt blocks and feed additives, enriching crops with soil Se, and even Se injections. Se primarily comes in either organic or inorganic forms. Though organic Se is more bioavailable, it is costlier than inorganic Se. This case study evaluates the impact of organic versus inorganic Se supplementation on ewe Se status and immunocompetence in 110 Dorset-Rideau ewes during the late pregnancy and lactation periods. The sheep were located in Ponsonby, Ontario, Canada. Though immunocompetence was not significantly different between treatment groups, the ewes in the organic treatment groups had higher serum Se concentrations after trial day 40, showing the benefit of organic Se in improving Se status over time. Information © The Authors 2025

Selenium (Se) is an essential soil mineral that can be incorporated into animal feedstuffs. Because of a lack of soil Se in some regions, organic or inorganic supplementation strategies must be implemented to prevent deficiencies and promote optimal ovine health. Therefore, the objectives of this study were to assess how inorganic versus organic Se supplementation influenced ewe Se status and immune function during late gestation and postpartum. Dorset Rideau ewes (n = 110) were fed a Se deficient diet from gestation d 110 through postpartum d 49 and received one of four daily oral Se treatments diluted in 5 mL of sugar water: 0 mg Se, 0.3 mg inorganic Se, 0.3 mg organic Se, and 0.6 mg organic Se. Throughout the trial, the ewes received various immune challenges, including intramuscular immunizations with a novel antigen (ovalbumin; OVA) on trial d 0 and 10, an intradermal OVA challenge on d 20, and a lipopolysaccharide (LPS) endotoxin challenge on trial d 49. The organic Se treatment groups had higher serum Se concentrations on most trial days compared to the 0.3 mg inorganic and control groups (P < 0.05). No significant treatment differences were found for the dermal hypersensitivity response to OVA, anti-OVA antibody response, glutathione peroxidase activity, cytokine response, cortisol response, or rectal temperature (P > 0.05). However, 4 h post-LPS injection, the serum albumin concentration was significantly lower in the 0.3 mg inorganic group compared to both organic Se groups, potentially indicating a higher degree of inflammation in the ewes supplemented with the inorganic Se. The results of this study indicate that organic Se supplementation can promote a higher Se status in ewes over time, but Se supplementation during this study period did not affect tested immunological parameters. This lack of difference in immune responsiveness between groups may be due to an absence of true serum Se deficiencies in the Se-deficient group or the levels of Se supplementation being insufficient to significantly improve immunocompetence.

Heat stress (HS) can affect gut barrier integrity, leading to a leaky gut and elevated enteric bacterial LPS endotoxin levels in the circulation. This LPS can induce systemic inflammation manifesting as the acute-phase response, which includes a febrile response that may compromise heat dissipation from the body during HS. To assess the effects of HS, peripheral blood mononuclear cells (PBMC) were isolated from dairy cows that were previously stress phenotyped based on their 4-h serum cortisol response to Escherichia coli LPS (200 ng/kg administered i.m.). After stress phenotyping, a population of dairy calves (n = 260), 8 high stress responder (HSR; +1 SD from the mean, >956.0 pg/mL), 11 middle stress responder (MSR; ± SD around the mean of 573.4 pg/mL), and 11 low stress responder (LSR; -1 SD from the mean, <190.8 pg/mL) stress-responding animals were selected for the study. The PBMC were later isolated and subjected to a heat shock challenge (HSC) in vitro at 42°C for 4 h then returned to 37°C where the control plates remained. Cell viability and proliferation were assessed, culture supernatants were collected to assess cytokine and chemokine secretion, and total RNA was extracted to assess candidate gene expression. There was a significant increase in the apoptosis of PBMC from the HSR and MSR, as compared with the LSR group post-HSC. However, there was a significant increase in necrosis in the LSR PBMC as compared with other groups following HSC. Proinflammatory and anti-inflammatory cytokine and chemokine production, specifically IFN-γ, IL-8, and MCP-1, was influenced by HSC and different across treatment groups. Finally, there was a significant increase in the expression of HSP90 and HSP70 genes in HSC MSR PBMC compared with the CNT MSR PBMC. Collectively, these results demonstrate that PBMC from variable stress-responding cows respond differently to the HSC. Future research is warranted to investigate if this phenotype can be used to improve the HS resilience of dairy cattle through selective breeding.

Vitamin D (VD) plays a critical role in human health, with deficiencies linked to a range of adverse outcomes, including compromised immune function and increased disease risk. While environmental factors such as sunlight exposure and diet influence circulating VD levels, genetic variation is a significant and underappreciated contributor to interindividual differences in serum 25-hydroxyvitamin D [25(OH)D] concentrations. This review provides a comprehensive summary of genetic variants in key genes involved in VD synthesis (e.g., DHCR7, cyp2r1, cyp27b1), transport (GC), and metabolism (cyp24a1, cyp3a4), as well as in cholesterol transport proteins (SCARB1, CD36, NPC1L1). We examine how single-nucleotide polymorphisms (SNPs) and rare mutations in these genes affect enzyme activity, VD bioavailability, and overall 25(OH)D status. Importantly, we highlight evidence supporting gene-by-environment interactions and population-specific allele frequencies that further shape individual VD responses. In the context of clinical nutrition and precision health, these findings support the development of genomic risk scores (GRSs) to identify individuals at risk for deficiency or toxicity and guide personalized VD supplementation strategies. Regular monitoring of serum 25(OH)D alongside genetic screening may improve clinical outcomes by helping to achieve optimal VD immunosufficiency while minimizing the risk of adverse effects.

Rhabdoviral vectors can induce lysis of cancer cells. While studied almost exclusively at 37 °C, viruses are subject to a range of temperatures in vivo , including temperatures ≤31 °C. Despite potential implications, the effect of temperatures <37 °C on the performance of rhabdoviral vectors is unknown. We investigated the effect of low anatomical temperatures on two rhabdoviruses, vesicular stomatitis virus (VSV) and Maraba virus (MG1). Using a metabolic resazurin assay, VSV- and MG1-mediated oncolysis was characterized in a panel of cell lines at 28, 31, 34 and 37 °C. The oncolytic ability of both viruses was hindered at 31 and 28 °C. Cold adaptation of both viruses was attempted as a mitigation strategy. Viruses were serially passaged at decreasing temperatures in an attempt to induce mutations. Unfortunately, the cold-adaptation strategies failed to potentiate the oncolytic activity of the viruses at temperatures <37 °C. Interestingly, we discovered that viral replication was unaffected at low temperatures despite the abrogation of oncolytic activity. In contrast, the proliferation of cancer cells was reduced at low temperatures. Equivalent oncolytic effects could be achieved if cells at low temperatures were treated with viruses for longer times. This suggests that rhabdovirus-mediated oncolysis could be compromised at low temperatures in vivo where therapeutic windows are limited.

Despite regulatory elements such as long non - coding RNAs representing most of the transcriptome, the functional understanding of long non - coding RNAs in relation to major health conditions including bovine mastitis is limited. This study examined the milk somatic cell transcriptome from udder quarters of 6 Holstein dairy cows to identify differentially expressed long non - coding RNAs using RNA - Sequencing. Ninety - four differentially expressed long non - coding RNAs are identified, 5 of which are previously annotated for gene name and length, 11 are annotated for gene name and 78 are novel, having no gene name or length previously annotated. Significant inflammatory response and regulation of immune response pathways (false discovery rate < 0.05) are associated with the differentially expressed long non - coding RNAs. QTL annotation analysis revealed 31 QTL previously annotated in the genomic regions of the 94 differentially expressed long non - coding RNAs, and the majority are associated with milk traits. This research provides a better understanding of long non - coding RNAs regulatory elements in milk somatic cells, which may enhance current breeding strategies for more adaptable or high mastitis resistant cattle.

Gastrointestinal nematodes (GINs) are a major constraint to the sheep industry. Infected animals can develop clinical signs, like anemia, hypoproteinemia, diarrhea, and in extreme cases death. The misuse of anthelmintics to treat infected animals has led to the development of GIN resistance making necessary the integration of different approaches to reduce the impact of GINs on the sheep industry. The application of transcriptomics using RNA-Sequencing technology to better understand the underlying genetic mechanisms of resistance to GIN can help accelerate the genetic gain. This study aimed to identify insertion and deletions (INDELs) responsible for alternative splicing in Rideau x Dorset crossbred sheep with different immune profiles under natural exposure to gastrointestinal nematodes using RNA-Sequencing. High (H) and medium (M) acute stress responders with the highest and lowest worm burden, after natural exposure to GIN, were selected for liver RNA extraction (H; n = 5 and M; n = 6). In addition, GIN-unexposed lambs (U; n = 4) were used as immunological controls. Quality control analyses were performed on fastq files using the CLC Bio Genomics workbench software including the guanine-cytosine (GC) content, ambiguous base content, Phred score, base coverage, nucleotide contributions, and over-represented sequence parameters. Pair-end sequence reads were aligned to the annotated Oar_rambouillet_v.2.0 ovine reference genome. After that, variant discovery analysis and functional consequence analysis were performed using CLC Bio Genomics workbench software to identify INDELs leading to amino acid changes and splice site events (SSEs). Genes associated with the list of INDELs leading to SSE were recovered from Ensembl BioMart. Unique INDELs with SSEs for H, M, and U groups (162, 244, and 161, respectively) and shared (372) among groups were identified. Among them, 4 INDELS with SSE uniquely identified in the M group were located within the NLRC5, SIGLEC1, CFD, and STAT6 genes related to the immune system. Significant enriched metabolic pathways (FDR< 0.05) were identified using the list of genes with INDELs that led to SSEs unique for each group and shared among groups using Reactome. Metabolic pathways related to the immune system response such as cross-presentation of soluble exogenous antigens (endosomes) and NIK noncanonical NF-kB signaling pathways were identified in the M group. These results can help to better understand the mechanisms responsible for the immune response of sheep to GIN.

Cattle produce Abs with an H chain ultralong CDR3 (40-70 aa). These Abs have been shown to have features such as broad neutralization of viruses and are investigated as human therapeutics. A common issue in sequencing the bovine BCR repertoire is the sequence length required to capture variable (V) and isotype gene information. This study aimed to assess the use of Oxford Nanopore Technologies' MinION platform to perform IgM BCR repertoire sequencing to assess variation in the percentage of ultralong CDR3s among dairy cattle. Blood was collected from nine Holstein heifers. B cells were isolated using magnetic bead-based separation, RNA was extracted, and IgM+ transcripts were amplified using PCR and sequenced using a MinION R10.4 flow cell. The distribution of CDR3 lengths was trimodal, and the percentage of ultralong CDR3s ranged among animals from 2.32 to 20.13% in DNA sequences and 1.56% to 17.02% in productive protein sequences. V segment usage varied significantly among heifers. Segment IGHV1-7, associated with ultralong CDR3s, was used in 5.8-24.2% of sequences; usage was positively correlated with ultralong CDR3 production (r = 0.99, p < 0.01). To our knowledge, this is the first study to sequence the bovine BCR repertoire using Oxford Nanopore Technologies and demonstrates the potential for cost-efficient long-read repertoire sequencing in cattle without assembly. Findings from this study support literature describing the distribution of length and percentage of ultralong CDR3s. Future studies will investigate changes in the bovine BCR repertoire associated with age, antigenic exposure, and genetics.

This study aimed to characterize the development of systemic and colon tissue resident B and γδ T cells in newborn calves from birth until weaning. At birth, calves have limited capacity to initiate immune responses, and the immune system gradually matures over time. Gamma delta (γδ) T cells are an important lymphocyte subset in neonatal calves that confer protection and promote immune tolerance. A total of 36 newborn calves were enrolled in a longitudinal study to characterize how systemic and colon tissue resident B and γδ T cells develop from birth until weaning. Blood and colon biopsy samples were collected on d 2, 28, and 42 to determine the proportions of various B and γδ T cell subsets by flow cytometry. We classified γδ T cells into different functional subsets according to the level of expression intensity of the coreceptors WC1.1 (effector function) and WC1.2 (regulatory function). Furthermore, naïve B cells were classified based on the expression IgM receptor, and activation state was determined based on expression of CD21 and CD32, 2 receptors with opposing signals involved in B cell activation in early life. Additional colon biopsy samples were used for 16S sequencing, and microbial diversity data is reported. At birth, γδ T cells were the most abundant lymphocyte population in blood, accounting for 58.5% of the lymphocyte pool, after which the proportions of these cells declined to 38.2% after weaning. The proportion of γδ T cells expressing WC1.1 decreased by 50% from d 2 to d 28, whereas no change was observed in the expression of WC1.2. In the colon, there was a 50% increase of γδ T cells after weaning and the proportion of WC1.2+ γδ T cells doubled from d 28 to 42. The proportion of IgM+ B lymphocytes in blood increased from 23.6% at birth to 30% after weaning, were the proportion of B cells expressing CD21 increased by 25%, while the proportion of B cells expressing CD32 decreased by 30%. While no changes were observed for the overall proportion of IgM+ B lymphocytes in the colon, there was a 6-fold increase in the proportion of CD21+ B cells from pre (d 28) to postweaning (d 42). Microbial diversity increased from d 2 of life to 28 and declined abruptly after weaning. The reduction in microbial diversity during weaning was negatively correlated with the increase in all γδ T cell subsets and CD21+ B cells. These data suggest that developmental adaptations after birth coordinate expansion of γδ T cells to provide early systemic protection, as well as to steer immune tolerance, while B cells mature over time. Additionally, the increase of colonic γδ T cells on d 42 suggests a protective role of these cells during weaning.

Gastrointestinal nematodes (GINs) can be a major constraint and global challenge to the sheep industry. These nematodes infect the small intestine and abomasum of grazing sheep, causing symptoms such as weight loss, diarrhea, hypoproteinemia, and anemia, which can lead to death. The use of anthelmintics to treat infected animals has led to GIN resistance, and excessive use of these drugs has resulted in residue traced in food and the environment. Resistance to GINs can be measured using multiple traits, including fecal egg count (FEC), Faffa Malan Chart scores, hematocrit, packed cell volume, eosinophilia, immunoglobulin (Ig), and dagginess scores. Genetic variation among animals exists, and understanding these differences can help identify genomic regions associated with resistance to GINs in sheep. Genes playing important roles in the immune system were identified in several studies in this review, such as the CFI and MUC15 genes. Results from several studies showed overlapping quantitative trait loci (QTLs) associated with multiple traits measuring resistance to GINs, mainly FEC. The discovery of genomic regions, positional candidate genes, and QTLs associated with resistance to GINs can help increase and accelerate genetic gains in sheep breeding programs and reveal the genetic basis and biological mechanisms underlying this trait.

Vitamin D is most known for its role in the development and maintenance of the skeletal system. However, recent studies have found that vitamin D modulates the immune system, and at sufficient levels supports optimal immune function. Previous research has examined how vitamin D levels change seasonally and during immune stress challenges in both humans and cattle, but not sheep. Our study aimed to investigate the changes in the vitamin D status of sheep throughout the year in Southern Ontario as well as in response to a bacterial endotoxin challenge. Vitamin D was found to be significantly lower in spring when compared to summer and early winter levels. No significant differences were found in vitamin D levels among any measured time points during the immune challenge, although a trending increase was found 4hr post-challenge. Overall, this study demonstrated how vitamin D levels in sheep change throughout the year, and slightly during endotoxin challenge. Given the importance of vitamin D in regulating optimal immune function, more investigation of these changes in vitamin D levels is warranted in terms of supporting optimal immune function.

In cattle, colostral maternal immunoglobulins and lymphocytes transfer across the neonate’s intestinal epithelium to provide protection against pathogens. This study aimed to compare repertoires of B cell populations in blood and colostrum in cows for the first time, with an emphasis on ultralong complementarity determining region 3 (CDR3, ≥40 amino acids). Blood mononuclear cells (BMCs, n= 7) and colostral cells (n = 7) were isolated from Holstein-Friesian dairy cows. Magnetic-activated cell sorting was used to capture IgM and IgG B cells from BMCs. Colostral cells were harvested by centrifugation. RNA was extracted and cDNA was produced; IgM and IgG transcripts were amplified using polymerase chain reactions. Amplicons were sequenced using the Nanopore Native barcoding kit 24 V14 and MinION with R10.4 flow cells. In colostrum, there was a significantly greater percentage of IgM B cells with ultralong CDR3s (8.09% ± 1.73 standard error of the mean) compared to blood (4.22% ± 0.70, p = 0.05). There was a significantly greater percentage of IgG B cells in colostrum with ultralong CDR3s (12.98% ± 1.98) compared to blood (6.61% ± 1.11, p = 0.05). A higher percentage of IgM and IgG B cells with ultralong CDR3s in colostrum may be indicative of a potential role in protecting the neonate.

Vitamin K (VK) is an essential micronutrient impacting many systems in the body. This lipid-soluble vitamin is found in various plant and animal products and is absorbed via the lymphatic system. This biomolecule’s importance to human health includes but is not limited to its promotion of brain, cardiovascular, bone, and immune functions. These biological properties are also necessary for maintaining domesticated animal health. The synergistic impact of both VK and vitamin D (VD) maximizes these health benefits, specifically for the circulatory and skeletal systems. This manuscript reviews VK’s properties, molecular structures, nutrikinetics, mechanisms of action, daily requirements, safety in supplemental form, biomarkers used for its detection, and impacts on various organs. The purpose of synthesizing this information is to evaluate the potential uses of VK for the treatment or prevention of diseases.

Infections with gastrointestinal nematodes (GINs) reduce the economic efficiency of sheep operations and compromise animal welfare. Understanding the host’s response to GIN infection can help producers identify animals that are naturally resistant to infection. The objective of this study was to characterize the hepatic transcriptome of sheep that had been naturally exposed to GIN parasites. The hepatic transcriptome was studied using RNA-Sequencing technology in animals characterized as high (n = 5) or medium (n = 6) based on their innate immune acute-phase (AP) response phenotype compared with uninfected controls (n = 4), and with biased antibody-mediated (AbMR, n = 5) or cell-mediated (CMR, n = 5) adaptive immune responsiveness compared to uninfected controls (n = 3). Following the assessment of sheep selected for innate responses, 0, 136, and 167 genes were differentially expressed (DE) between high- and medium-responding animals, high-responding and uninfected control animals, and medium-responding and uninfected control animals, respectively (false discovery rate (FDR) < 0.05, and fold change |FC| > 2). When adaptive immune responses were assessed, 0, 53, and 57 genes were DE between antibody- and cell-biased animals, antibody-biased and uninfected control animals, and cell-biased and uninfected control animals, respectively (FDR < 0.05, |FC| > 2). Functional analyses identified enriched gene ontology (GO) terms and metabolic pathways related to the innate immune response and energy metabolism. Six functional candidate genes were identified for further functional and validation studies to better understand the underlying biological mechanisms of host responses to GINs. These, in turn, can potentially help improve decision making and management practices to increase the overall host immune response to GIN infection.

Selenium (Se) is an essential nutrient that has gained attention for its impact on the human immune system. The purpose of this review is to explore Se’s immunomodulatory properties and to make up-to-date information available so novel therapeutic applications may emerge. People acquire Se through dietary ingestion, supplementation, or nanoparticle applications. These forms of Se can beneficially modulate the immune system by enhancing antioxidant activity, optimizing the innate immune response, improving the adaptive immune response, and promoting healthy gut microbiota. Because of these many actions, Se supplementation can help prevent and treat pathogenic diseases, autoimmune diseases, and cancers. This review will discuss Se as a key micronutrient with versatile applications that supports disease management due to its beneficial immunomodulatory effects. Further research is warranted to determine safe dosing guidelines to avoid toxicity and refine the application of Se in medical treatments.

Gastrointestinal nematode (GIN) infections are considered the most important disease of grazing sheep and due to increasing anthelmintic resistance, chemical control alone is inadequate. Resistance to Gastrointestinal nematode infection is a heritable trait, and through natural selection many sheep breeds have higher resistance. Studying the transcriptome from GIN-exposed and GIN-unexposed sheep using RNA-Sequencing technology can provide measurements of transcript levels associated with the host response to Gastrointestinal nematode infection, and these transcripts may harbor genetic markers that can be used in selective breeding programs to enhance disease resistance. The objective of this study was to compare liver transcriptomes of sheep naturally exposed to Gastrointestinal nematode s, with either high or low parasite burdens, to GIN-unexposed control sheep in order to identify key regulator genes and biological processes associated with Gastrointestinal nematode infection. Differential gene expression analysis revealed no significant differentially expressed genes (DEG) between sheep with a high or low parasite burden (p-value ≤0.01; False Discovery Rate (FDR) ≤ 0.05; and Fold-Change (FC) of > ±2). However, when compared to the control group, low parasite burden sheep showed 146 differentially expressed genes (64 upregulated and 82 downregulated in the low parasite burden group relative to the control), and high parasite burden sheep showed 159 differentially expressed genes (57 upregulated and 102 downregulated in the low parasite burden group relative to the control) (p-value ≤0.01; FDR ≤0.05; and FC of > ±2). Among these two lists of significant differentially expressed genes, 86 differentially expressed genes (34 upregulated, 52 downregulated in the parasited group relative to the control) were found in common between the two parasite burden groups compared to the control (GIN-unexposed sheep). Functional analysis of these significant 86 differentially expressed genes found upregulated genes involved in immune response and downregulated genes involved in lipid metabolism. Results of this study offer insight into the liver transcriptome during natural Gastrointestinal nematode exposure that helps provide a better understanding of the key regulator genes involved in Gastrointestinal nematode infection in sheep.

N-acetylcysteine (NAC), an acetylated derivative of the amino acid L-cysteine, has been widely used as a mucolytic agent and antidote for acetaminophen overdose since the 1960s and the 1980s, respectively. NAC possesses antioxidant, cytoprotective, anti-inflammatory, antimicrobial, and mucolytic properties, making it a promising therapeutic agent for a wide range of diseases in both humans and domesticated animals. Oxidative stress and inflammation play a major role in the onset and progression of all these diseases. NAC's primary role is to replenish glutathione (GSH) stores, the master antioxidant in all tissues; however, it can also reduce levels of pro-inflammatory tumor necrosis factor-alpha (TNF-∝) and interleukins (IL-6 and IL-1β), inhibit the formation of microbial biofilms and destroy biofilms, and break down disulfide bonds between mucin molecules. Many experimental studies have been conducted on the use of NAC to address a wide range of pathological conditions; however, its effectiveness in clinical trials remains limited and studies often have conflicting results. The purpose of this review is to provide a concise overview of promising NAC usages for the treatment of different human and domestic animal disorders.