Immunological Functions Research Articles

Identification of CCCH-type zinc finger antiviral protein 1 (ZAP) gene from Pacific white shrimp (Penaeus vannamei): Characterization and expression analysis in response to viral infection.

Zinc-finger proteins (ZFPs) are a huge family that exert multiple roles in the cells. ZFPs could be divided into nine types based on the numbers and positions of conserved Cys and His residues, in which CCCH-type ZFP was one of the most widely studied types. CCCH-type zinc finger antiviral protein 1 (ZAP), a CCCH-type ZFP that can inhibit the replication of certain RNA viruses and DNA viruses by mediating degradation of viral RNA and repressing mRNA translation, plays significant roles in the host innate immune defenses against viral infections. Presently, there have been numerous reports investigating the antiviral ability of ZAP, while no data is available about ZAP gene in the species of shrimps or even crustaceans. In this study, a novel protein containing CCCH-type zinc finger motifs (ZnF-CCCH), CCCH-type zinc finger antiviral protein 1 (ZAP) gene, was identified from Pacific white shrimp (Penaeus vannamei) and its role in antiviral immunity was further investigated. Similar to mammalian ZAPs, in addition to ZnF-CCCH, PvZAP also possesses central WWE domains and C-terminal PARP domain. Phylogenetic analysis showed that PvZAP was close to that of the crustacean Pacific oyster, separating from the cluster of vertebrate ZAP proteins. Upon in vivo infection by IHHNV, gene expression of PvZAP was strongly up-regulated in the hepatopancreas and gills of both adult and juvenile shrimps, where adult individuals showed higher fold changes of up-regulation than in juvenile individuals. These results suggested that PvZAP might play an important role in the innate immune defense of Pacific white shrimp against IHHNV infection. This allows us to gain new insights into the immunological function of ZAP in the innate immunity of shrimp species and even crustaceans.

Effects of different water quality regulators on growth performance, immunologic function, and domestic water quality of GIFT tilapia.

Water quality regulation is widely recognized as a highly effective strategy for disease prevention in the field of aquaculture, and it holds significant potential for the development of sustainable aquaculture. Herein, four water quality regulators, including potassium monopersulfate (KMPS), tetrakis hydroxymethyl phosphonium sulfate (THPS), bacillus subtilis (BS), and chitosan (CS), were added to the culture water of Oreochromis niloticus (GIFT tilapia) every seven days. Subsequently, the effects of these four water quality regulators on GIFT tilapia were comprehensively evaluated by measuring the water quality index of daily growth-related performance and immune indexes of GIFT tilapia. The findings indicated that implementing the four water quality regulators resulted in a decrease in the content of ammonia nitrogen, active phosphate, nitrite, total organic carbon (TOC), and chemical oxygen demand (COD) in the water. Additionally, these regulators were found to maintain dissolved oxygen (DO) levels and pH of the water effectively. Furthermore, using these regulators demonstrated positive effects on various physiological parameters of GIFT tilapia, including improvements in final body weight, weight gain rate (WGR), specific growth rate (SGR), condition factor (CF), feed conversion ratio (FCR), spleen index (SI), hepato-somatic index (HSI), immune cell count, the activity of antioxidant-related enzymes (Nitric oxide, NO and Superoxide dismutase, SOD), and mRNA expression levels of immunity-related factors (Tumor Necrosis Factor-alpha, TNF-α and Interleukin-1 beta, IL-1β) in the liver and spleen. Notably, the most significant improvements were observed in the groups treated with the BS and CS water quality regulators. Moreover, BS and CS groups exhibited significantly higher serum levels of albumin (ALB) and total protein (TP) (P < 0.05), whereas the other indicators showed no significant difference (P > 0.05) compared to the control group. However, the KMPS and THPS groups of GIFT tilapia exhibited significantly higher serum levels of aspartate aminotransferase (AST), alanine transaminase (ALT), creatinine (CRE) and blood urea nitrogen (BUN) (P < 0.05), whereas they exhibited significantly decreased HSI (P < 0.05). In addition, the partially pathological observations revealed the presence of cell vacuolation, nuclear shrinkage, and pyknosis within the liver. In conclusion, these four water quality regulators, mainly BS and CS, could improve the growth performance and immunity of GIFT tilapia to varying degrees by regulating the water quality and then further increasing the expression levels of immune-related factors or the activity of antioxidant-related enzymes of GIFT tilapia. On the contrary, the prolonged use of KMPS and THPS may gradually diminish their growth-enhancing properties and potentially hinder the growth of GIFT tilapia.

Safety and aesthetic outcomes of using fillers with different cross-linking agents. A case report.

Of the several dermal fillers developed in recent decades, hyaluronic acid fillers have become the material of choice. They are safe, long-lasting, non-immunogenic, available to most patients, and can be removed with hyaluronidase. Unfortunately, early and delayed complications can also occur after HA filler injection. Below, we present the case of a 42-year-old patient who had complications after the aesthetic procedure using hyaluronic acid dermal fillers in the past. Surprisingly, the treatment performed with hyaluronic acid cross-linked with another cross-linking agent was without complications. The affected places were the chin and malar area. In 2021, after performing augmentation with hyaluronic acid in the chin area, a patient developed swelling, which subsided after using hyaluronidase (Hylase Dessau 300 I.E.) and corticosteroids. The patient repeated the procedure in 2022, where she was administered 2 ml of hyaluronic acid in July 2022. About 3 weeks after injection, oedema and nodules appeared at the injection site in the zygomatic/malar area; after using Prednisone, the changes subsided. In September 2022, 3 ml of PEG-cross-linked hyaluronic acid was successfully performed with no side effects. In the described case, an important role was played by the ability of the hyaluronic acid hydrogel to modulate human immunological functions, which was associated with a very low risk of immune-related side effects and accompanying cellulitic processes.

Central regulation of stress-evoked peripheral immune responses.

Stress-linked psychiatric disorders, including anxiety and major depressive disorder, are associated with systemic inflammation. Recent studies have reported stress-induced alterations in haematopoiesis that result in monocytosis, neutrophilia, lymphocytopenia and, consequently, in the upregulation of pro-inflammatory processes in immunologically relevant peripheral tissues. There is now evidence that this peripheral inflammation contributes to the development of psychiatric symptoms as well as to common co-morbidities of psychiatric disorders such as metabolic syndrome and immunosuppression. Here, we review the specific brain and spinal regions, and the neuronal populations within them, that respond to stress and transmit signals to peripheral tissues via the autonomic nervous system or neuroendocrine pathways to influence immunological function. We comprehensively summarize studies that have employed retrograde tracing to define neurocircuits linking the brain to the bone marrow, spleen, gut, adipose tissue and liver. Moreover, we highlight studies that have used chemogenetic or optogenetic manipulation or intracerebroventricular administration of peptide hormones to control somatic immune responses. Collectively, this growing body of literature illustrates potential mechanisms through which stress signals are conveyed from the CNS to immune cells to regulate stress-relevant behaviours and comorbid pathophysiology.

The role of the symbiotic microecosystem in cancer: gut microbiota, metabolome, and host immunome.

The gut microbiota is not just a simple nutritional symbiosis that parasitizes the host; it is a complex and dynamic ecosystem that coevolves actively with the host and is involved in a variety of biological activities such as circadian rhythm regulation, energy metabolism, and immune response. The development of the immune system and immunological functions are significantly influenced by the interaction between the host and the microbiota. The interactions between gut microbiota and cancer are of a complex nature. The critical role that the gut microbiota plays in tumor occurrence, progression, and treatment is not clear despite the already done research. The development of precision medicine and cancer immunotherapy further emphasizes the importance and significance of the question of how the microbiota takes part in cancer development, progression, and treatment. This review summarizes recent literature on the relationship between the gut microbiome and cancer immunology. The findings suggest the existence of a "symbiotic microecosystem" formed by gut microbiota, metabolome, and host immunome that is fundamental for the pathogenesis analysis and the development of therapeutic strategies for cancer.

Exploring the relationship between lactate metabolism and immunological function in colorectal cancer through genes identification and analysis.

Introduction: Metabolic dysregulation is a widely acknowledged contributor for the development and tumorigenesis of colorectal cancer (CRC), highlighting the need for reliable prognostic biomarkers in this malignancy. Methods: Herein, we identified key genes relevant to CRC metabolism through a comprehensive analysis of lactate metabolism-related genes from GSEA MsigDB, employing univariate Cox regression analysis and random forest algorithms. Clinical prognostic analysis was performed following identification of three key genes, and consistent clustering enabled the classification of public datasets into three patterns with significant prognostic differences. The molecular pathways and tumor microenvironment (TME) of these patterns were then investigated through correlation analyses. Quantitative PCR was employed to quantify the mRNA expression levels of the three pivotal genes in CRC tissue. Single-cell RNA sequencing data and fluorescent multiplex immunohistochemistry were utilized to analyze relevant T cells and validate the correlation between key genes and CD4+ T cells. Results: Our analysis revealed that MPC1, COQ2, and ADAMTS13 significantly stratify the cohort into three patterns with distinct prognoses. Additionally, the immune infiltration and molecular pathways were significantly different for each pattern. Among the key genes, MPC1 and COQ2 were positively associated with good prognosis, whereas ADAMTS13 was negatively associated with good prognosis. Single-cell RNA sequencing (scRNA-seq) data illustrated that the relationship between three key genes and T cells, which was further confirmed by the results of fluorescent multiplex immunohistochemistry demonstrating a positive correlation between MPC1 and COQ2 with CD4+ T cells and a negative correlation between ADAMTS13 and CD4+ T cells. Discussion: These findings suggest that the three key lactate metabolism genes, MPC1, COQ2, and ADAMTS13, may serve as effective prognostic biomarkers and support the link between lactate metabolism and the immune microenvironment in CRC.

Association between the Respiratory Microbiome and Plasma Microbial Extracellular Vesicles in Intubated Patients.

Extracellular vesicles (EVs) regulate various cellular and immunological functions in human diseases. There is growing interest in the clinical role of microbial EVs in pneumonia. However, there is a lack of research on the correlation between lung microbiome with microbial EVs and the microbiome of other body sites in pneumonia. We investigated the co-occurrence of lung microbiome and plasma microbe-derived EVs (mEVs) in 111 samples obtained from 60 mechanically ventilated patients (41 pneumonia and 19 non-pneumonia cases). The microbial correlation between the two samples was compared between the pneumonia and non-pneumonia cases. Bacterial composition of the plasma mEVs was distinct from that of the lung microbiome. There was a significantly higher correlation between lung microbiome and plasma mEVs in non-pneumonia individuals compared to pneumonia patients. In particular, Acinetobacter and Lactobacillus genera had high correlation coefficients in non-pneumonia patients. This indicates a beneficial effect of mEVs in modulating host lung immune response through EV component transfer.

The cover of an ear thermometer probe as a split-thickness skin graft mold in external auditory canal reconstruction.

Maintaining the patency of the external auditory canal (EAC) during reconstruction is important because of its physiological role in hearing and immunological protective functions. The curved shape of the EAC presents a challenge when performing a skin graft. One of the key points for a successful skin graft is to ensure compression on the wound bed, and many novel methods, including prefabricated ear molds, have been reported for this purpose. In this study, we present a case of a skin graft performed to reconstruct a skin defect following excision of actinic keratosis in the EAC, using the cover of an ear thermometer probe as a mold for the graft to match the curvature of the EAC. This is an economical and practical method for secure compression dressing of a skin graft in the EAC.

The Role of Benson's and Mitchell's Relaxation Techniques in the Management of Premenstrual Syndrome: An In-Depth Review.

Premenstrual syndrome (PMS) is a menstrual disorder characterized by physical, behavioral, and emotional symptoms typically occurring during the luteal phase. These symptoms are usually mild and somatic and often subside during or just before the start of menstruation. Medical professionals employ pharmacological and non-pharmacological treatments as the primary approach to managing PMS. One effective non-pharmacological method is Laura Mitchell's physiological relaxation treatment, which has been shown to enhance immunological function, reduce depression, and improve the overall quality of life. Another beneficial technique is Benson's relaxation technique, established by Herbert Benson in 1970, providing a simple yet powerful stress-release strategy. For this study, research papers were searched using various reputable databases such as PubMed, Scopus, Web of Science, and Google Scholar websites, with data collected up to the end of 2021. The publication dates of the review articles were not restricted, allowing for a comprehensive overview. However, it is important to note that only a limited number of accessible studies have been found, underscoring the need for further research. Future investigations should focus on high-quality evidence with reliable outcome measures to draw more conclusive results about which relaxation technique offers better relief for PMS.

Interleukin-8 involved in Nile Tilapia (Oreochromis niloticus) against bacterial infection

Interleukin 8 (IL8) is vital in promoting inflammation and is a crucial mediator in various physiopathological processes while influencing immunological function. The effect of IL8 on the immunological response to acute bacterial infections in Nile tilapia (Oreochromis niloticus) remains unknown. This work found an IL8 gene from Nile tilapia (On-IL8). It includes a 285 bp open reading frame and codes for 94 amino acids. The transcript levels of On-IL8 were highest in the head-kidney tissue and sharply induced by Streptococcus agalactiae and Aeromonas hydrophila. Besides, in vitro experiments revealed that On-IL8 regulated a variety of immunological processes and promoted inflammatory responses. Moreover, On-IL8 suppressed the NF-κB signaling pathway, consistent with in vitro results. These significant findings serve as the basis for further investigation into how IL8 confers protection to bony fish in opposition to bacterial infections.

Pyrimidine metabolism regulator-mediated molecular subtypes display tumor microenvironmental hallmarks and assist precision treatment in bladder cancer.

Bladder cancer (BLCA) is a common urinary system malignancy with a significant morbidity and death rate worldwide. Non-muscle invasive BLCA accounts for over 75% of all BLCA cases. The imbalance of tumor metabolic pathways is associated with tumor formation and proliferation. Pyrimidine metabolism (PyM) is a complex enzyme network that incorporates nucleoside salvage, de novo nucleotide synthesis, and catalytic pyrimidine degradation. Metabolic reprogramming is linked to clinical prognosis in several types of cancer. However, the role of pyrimidine metabolism Genes (PyMGs) in the BLCA-fighting process remains poorly understood. Predictive PyMGs were quantified in BLCA samples from the TCGA and GEO datasets. TCGA and GEO provided information on stemness indices (mRNAsi), gene mutations, CNV, TMB, and corresponding clinical features. The prediction model was built using Lasso regression. Co-expression analysis was conducted to investigate the relationship between gene expression and PyM. PyMGs were overexpressed in the high-risk sample in the absence of other clinical symptoms, demonstrating their predictive potential for BLCA outcome. Immunological and tumor-related pathways were identified in the high-risk group by GSWA. Immune function and m6a gene expression varied significantly between the risk groups. In BLCA patients, DSG1, C6orf15, SOST, SPRR2A, SERPINB7, MYBPH, and KRT1 may participate in the oncology process. Immunological function and m6a gene expression differed significantly between the two groups. The prognostic model, CNVs, single nucleotide polymorphism (SNP), and drug sensitivity all showed significant gene connections. BLCA-associated PyMGs are available to provide guidance in the prognostic and immunological setting and give evidence for the formulation of PyM-related molecularly targeted treatments. PyMGs and their interactions with immune cells in BLCA may serve as therapeutic targets.

Effects of body mass index on the immune response within the first days after major stroke in humans

IntroductionImmunological alterations associated with increased susceptibility to infection are an essential aspect of stroke pathophysiology. Several immunological functions of adipose tissue are altered by obesity and are accompanied by chronic immune activation. The purpose of this study was to examine immune function (monocytes, granulocytes, cytokines) as a function of body mass index (BMI: 1st group: 25; 2nd group: 25 BMI 30; 3rd group: 30) and changes in body weight post stroke.MethodFat status was assessed using standardized weight measurements on days 1, 2, 3, 4, 5, and 7 after ischemic stroke in a cohort of 40 stroke patients and 16 control patients. Liver fat and visceral fat were assessed by MRI on day 1 or 2 [I] and on day 5 or 7 [II]. Leukocyte subpopulations in peripheral blood, cytokines, chemokines, and adipokine concentrations in sera were quantified. In a second cohort (stroke and control group, n = 17), multiple regression analysis was used to identify correlations between BMI and monocyte and granulocyte subpopulations.ResultsWeight and fat loss occurred from the day of admission to day 1 after stroke without further reduction in the postischemic course. No significant changes in liver or visceral fat were observed between MRI I and MRI II. BMI was inversely associated with IL-6 levels, while proinflammatory cytokines such as eotaxin, IFN-β, IFN -γ and TNF-α were upregulated when BMI increased. The numbers of anti-inflammatory CD14+CD16+ monocytes and CD16+CD62L− granulocytes were reduced in patients with higher BMI values, while that of proinflammatory CD16dimCD62L+ granulocytes was increased.ConclusionA small weight loss in stroke patients was detectable. The data demonstrate a positive correlation between BMI and a proinflammatory poststroke immune response. This provides a potential link to how obesity may affect the clinical outcome of stroke patients.

Association Between Circulating 25-Hydroxy Vitamin D Receptor and Molecular Response in Multiple Myeloma.

&lt;b&gt;Background and Objective:&lt;/b&gt; Vitamin D Receptor (VDR) regulate several body processes related to metabolism, immunological function and oncogenesis. Low vitamin D levels are recognized as associated with a higher incidence of hematologic malignancies and poor outcomes. This study aims to determine whether vitamin D levels and VDR contribute to multiple myeloma (MM). &lt;b&gt;Materials and Methods:&lt;/b&gt; This study enrolled twenty-five patients diagnosed with MM. Ages and gender were matched between patients and healthy groups. Serum Protein Electrophoresis (SPEP) was detected for all patients. Also, serum 25-hydroxy vitamin D levels were recorded. The PCR products were submitted to Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) and Sanger sequencing to detect VDR gene polymorphism including (FokI, ApaI and Tru9I). &lt;b&gt;Results:&lt;/b&gt; This study revealed that an M spike was detected in five patients newly diagnosed with MM. According to vitamin D levels 84% of patients had a vitamin D deficiency. In the RFLP technique, FokI CT, ApaI AA and Tru9I GG genotypes were highly distributed in patients. Additionally, the MM group had a significant frequency of the T allele in the FokI (44.0%), the A allele in the ApaI (68.0%) and the A allele in the Tru9I (30.0%). &lt;b&gt;Conclusion:&lt;/b&gt; The SPEP is an easy-to-perform laboratory test that can be used to detect and quantify monoclonal proteins. Low vitamin D level of less than 20 ng mL&lt;sup&gt;&lt;/sup&gt;&lt;sup&gt;1&lt;/sup&gt; is associated with an increased prevalence of MM and a worse response to treatment. In addition, VDR gene polymorphisms may be a molecular marker of MM risk.

Choroid Plexus Volume Change-A Candidate for a New Radiological Marker of MS Progression.

(1) Background: Multiple sclerosis (MS) is an auto-immune, chronic, neuroinflammatory, demyelinating disease that affects mainly young patients. This progressive inflammatory process causes the chronic loss of brain tissue and results in a deterioration in quality of life. To monitor neuroinflammatory process activity and predict the further development of disease, it is necessary to find a suitable biomarker that could easily be used. In this research, we verify the usability of choroid plexus (CP) volume, a new MS biomarker, in the monitoring of the progression of multiple sclerosis disease. (2) Methods: A single-center, prospective study with three groups of patients was conducted based on the following groups: MS patients who received experimental cellular therapy (Treg), treatment-naïve MS patients and healthy controls. (3) Results: This study concludes that there is a correlation between the CPV/TIV (choroid plexus/total intracranial volume) ratio and the progress of multiple sclerosis disease-patients with MS (MS + Treg) had larger volumes of choroid plexuses. CPV/TIV ratios in MS groups were constantly and significantly growing. In the Treg group, patients with relapses had larger plexuses in comparison to the group with no relapses of MS. A similar correlation was observed for the GD+ group (patients with postcontrast enhancing plaques) compared against the non-GD group (patients without postcontrast enhancing plaques). (4) Conclusion: Choroid plexus volume, due to its immunological function, correlates with the inflammatory process in the central nervous system. We consider it to become a valuable radiological biomarker of MS activity.

ADAM17 targeting by human cytomegalovirus remodels the cell surface proteome to simultaneously regulate multiple immune pathways

Human cytomegalovirus (HCMV) is a major human pathogen whose life-long persistence is enabled by its remarkable capacity to systematically subvert host immune defenses. In exploring the finding that HCMV infection up-regulates tumor necrosis factor receptor 2 (TNFR2), a ligand for the pro-inflammatory antiviral cytokine TNFα, we found that the underlying mechanism was due to targeting of the protease, A Disintegrin And Metalloproteinase 17 (ADAM17). ADAM17 is the prototype 'sheddase', a family of proteases that cleaves other membrane-bound proteins to release biologically active ectodomains into the supernatant. HCMV impaired ADAM17 surface expression through the action of two virally-encoded proteins in its UL/b' region, UL148 and UL148D. Proteomic plasma membrane profiling of cells infected with an HCMV double-deletion mutant for UL148 and UL148D with restored ADAM17 expression, combined with ADAM17 functional blockade, showed that HCMV stabilized the surface expression of 114 proteins (P < 0.05) in an ADAM17-dependent fashion. These included reported substrates of ADAM17 with established immunological functions such as TNFR2 and jagged1, but also numerous unreported host and viral targets, such as nectin1, UL8, and UL144. Regulation of TNFα-induced cytokine responses and NK inhibition during HCMV infection were dependent on this impairment of ADAM17. We therefore identify a viral immunoregulatory mechanism in which targeting a single sheddase enables broad regulation of multiple critical surface receptors, revealing a paradigm for viral-encoded immunomodulation.

Molecular reshaping of phage-displayed Interleukin-2 at beta chain receptor interface to obtain potent super-agonists with improved developability profiles

Interleukin-2 (IL-2) engineered versions, with biased immunological functions, have emerged from yeast display and rational design. Here we reshaped the human IL-2 interface with the IL-2 receptor beta chain through the screening of phage-displayed libraries. Multiple beta super-binders were obtained, having increased receptor binding ability and improved developability profiles. Selected variants exhibit an accumulation of negatively charged residues at the interface, which provides a better electrostatic complementarity to the beta chain, and faster association kinetics. These findings point to mechanistic differences with the already reported superkines, characterized by a conformational switch due to the rearrangement of the hydrophobic core. The molecular bases of the favourable developability profile were tracked to a single residue: L92. Recombinant Fc-fusion proteins including our variants are superior to those based on H9 superkine in terms of expression levels in mammalian cells, aggregation resistance, stability, in vivo enhancement of immune effector responses, and anti-tumour effect.

In-Depth Proteomic Map of Innate Lymphoid Cells from Healthy Human Skin and Blood

Innate lymphoid cells (ILCs) are essential players in the skin-associated immune system, nevertheless little is known about their proteomes and proteomic diversity. In this study, we describe about 6,600 proteins constitutively expressed by ILC2s and ILC3s from healthy human skin and blood using state-of-the-art proteomics. Although the vast majority of proteins was expressed by both ILC subsets and in both compartments, the skin ILC2s and ILC3s were more distinct than their counterparts in blood. Only skin ILC3s expressed uniquely detected proteins. Our in-depth proteomic datasetallowed us to define the cluster of differentiation marker profiles of the ILC subsets, explore distribution and abundance of proteins known to have immunological functions, as well as identify subset-specific proteins that have not previously been implicated in ILC biology. Taken together, our analyses substantially expand understanding of the protein expression signatures of ILC subsets. Going forward, these proteomic datasets will serve as valuable resources for future studies of ILC biology.

Rural and urban exposures shape early life immune development in South African children with atopic dermatitis and nonallergic children.

Immunological traits and functions have been consistently associated with environmental exposures and are thought to shape allergic disease susceptibility and protection. In particular, specific exposures in early life may have more significant effects on the developing immune system, with potentially long-term impacts. We performed RNA-Seq on peripheral blood mononuclear cells (PBMCs) from 150 children with atopic dermatitis and healthy nonallergic children in rural and urban settings from the same ethnolinguistic AmaXhosa background in South Africa. We measured environmental exposures using questionnaires. A distinct PBMC gene expression pattern was observed in those children with atopic dermatitis (132 differentially expressed genes [DEGs]). However, the predominant influences on the immune cell transcriptome were related to early life exposures including animals, time outdoors, and types of cooking and heating fuels. Sample clustering revealed two rural groups (Rural_1 and Rural_2) that separated from the urban group (3413 and 2647 DEGs, respectively). The most significantly regulated pathways in Rural_1 children were related to innate activation of the immune system (e.g., TLR and cytokine signaling), changes in lymphocyte polarization (e.g., TH17 cells), and immune cell metabolism (i.e., oxidative phosphorylation). The Rural_2 group displayed evidence for ongoing lymphocyte activation (e.g., T cell receptor signaling), with changes in immune cell survival and proliferation (e.g., mTOR signaling, insulin signaling). This study highlights the importance of the exposome on immune development in early life and identifies potentially protective (e.g., animal) exposures and potentially detrimental (e.g., pollutant) exposures that impact key immunological pathways.

Unexpected death involving the spleen - an overview.

The spleen is located in the left upper quadrant of the abdominal cavity and has both immunological and haematological functions. A variety of quite different entities may be associated with sudden death due to splenic involvement. These range from simple traumatic disruption of the parenchyma of a normal spleen with marked intra-abdominal haemorrhage, to conditions such as malaria and infectious mononucleosis where splenomegaly predisposes to rupture. Haematological diseases such as malignancies and haemoglobinopathies may causes sudden death due to haemorrhage or red cell sequestration. Asplenia or polysplenia may be associated with significant congenital heart disease. Hyposplenia, both structural and functional, may also result in rapid demise from sometimes unusual bacterial infections. Vascular abnormalities causing death include entities such as splenic artery aneurysms. Thus, deaths from splenic pathology may be due to localised issues or may be part of more generalised disease. For this reason the autopsy in cases of splenic-associated deaths must be comprehensive and include special testing such as microbiological screening and/or haematologic/genetic evaluation.

Effect of Bacillus toyonensis BCT-7112T supplementation on growth performance, intestinal morphology, immune-related gene expression, and gut microbiome in Barbary ducks

This study aimed to investigate the effect of Bacillus toyonensis BCT-7112T supplementation on growth performance, intestinal morphology, immune-related gene expression, and the cecal microbiota of meat ducks. A total of 150 one-day-old male Barbary ducks were divided into 3 groups with 5 replicates (n=10 ducks per replicate) by completely randomized design and offered diets supplemented with the commercial product Toyocerin (containing 1×109B. toyonensis BCT-7112T viable spores/g product) at the levels of 0, 500, or 1,000 mg/kg (0, 500, or 1,000 ppm), respectively, for 8 wk. The results showed that although ducks in the 500 ppm B. toyonensis BCT-7112T group displayed numerically better values (e.g., weight gain and feed conversion ratio) than those in the control group, the growth performance of ducks fed diets supplemented with B. toyonensis BCT-7112T did not differ significantly from that of the control group (P > 0.05). There were no significant differences in the intestinal mucosal morphology of ducks across the experimental groups (P > 0.05). However, ducks in the 500 ppm B. toyonensis BCT-7112T group showed a trend of greater values, for example, villus height per crypt depth of duodenum (P=0.16) and ileum (P=0.12) compared with those in the control group. The relative expression of immune-related genes, for example, interferon (IFN) and interleukin-6 (IL-6) in the meat duck spleen was significantly lower in both B. toyonensis BCT-7112T groups at 14 d and 35 d than in the control group (P < 0.05). Beta diversity analysis of the cecal microbiota of ducks in either the 500 ppm or the 1,000 ppm B. toyonensis BCT-7112T group showed to have higher diversity than that in the control group, where at the phylum level, Bacteroidetes was the most abundant, followed by Firmicutes, and at the genus level, Bacteroides, Fusobacterium, and Ruminococcaceae were the top 3 most abundant genera. In conclusion, our study demonstrates that 500 ppm supplementation with B. toyonensis BCT-7112T in duck diets can reduce proinflammatory cytokine gene expression, improve immunological function, and increase the variety of microbial communities in the ceca of meat-type ducks.