Expression Of Immune Factors Research Articles

Integrated machine learning developed a prognosis-related gene signature to predict prognosis in oesophageal squamous cell carcinoma.

The mortality rate of oesophageal squamous cell carcinoma (ESCC) remains high, and conventional TNM systems cannot accurately predict its prognosis, thus necessitating a predictive model. In this study, a 17-gene prognosis-related gene signature (PRS) predictive model was constructed using the random survival forest algorithm as the optimal algorithm among 99 machine-learning algorithm combinations based on data from 260 patients obtained from TCGA and GEO. The PRS model consistently outperformed other clinicopathological features and previously published signatures with superior prognostic accuracy, as evidenced by the receiver operating characteristic curve, C-index and decision curve analysis in both training and validation cohorts. In the Cox regression analysis, PRS score was an independent adverse prognostic factor. The 17 genes of PRS were predominantly expressed in malignant cells by single-cell RNA-seq analysis via the TISCH2 database. They were involved in immunological and metabolic pathways according to GSEA and GSVA. The high-risk group exhibited increased immune cell infiltration based on seven immunological algorithms, accompanied by a complex immune function status and elevated immune factor expression. Overall, the PRS model can serve as an excellent tool for overall survival prediction in ESCC and may facilitate individualized treatment strategies and predction of immunotherapy for patients with ESCC.

Correlation between Immune Factor Expression and Prognosis of Plasma Cell Mastitis Surgery and its Predictive Value for Prognosis

Background: To study the correlation between the expression of immune factors and the prognosis of surgical treatment of plasma cell mastitis (PCM) and to analyze its predictive value for the prognosis of patients. Methods: 89 female patients with PCM treated in our hospital from June 2020 to September 2022 were divided into good prognosis group (69 cases) and poor prognosis group (20 cases). Logistic regression was used to analyze the influencing factors of poor prognosis of surgical treatment for PCM, and to explore the correlation between these immune factors and the prognosis of surgical treatment for PCM. Draw the receiver operating characteristic (ROC) curve to analyze the predictive value of the above indexes for the prognosis of patients with PCM. Results: After 4 weeks of treatment, the levels of tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) were significantly lower than before treatment (p < 0.05), and the level of interleukin 10 (IL-10) was significantly higher than before treatment (p < 0.05). At the time of admission, there was no significant difference in the clinical data and the levels of TNF-α, IL-6 and IL-10 between the two groups (p > 0.05). After 4 weeks of treatment, the indexes of TNF-α and IL-6 in the poor prognosis group were higher than those in the good prognosis group (p < 0.05). Logistic regression analysis showed that the levels of TNF-α (odds ratio (OR) = 1.551, 95% confidence interval (95% CI): 1.276–1.886) and IL-6 (OR = 1.082, 95% CI: 1.046–1.119) were increased, which were risk factors for the prognosis of PCM (OR >1). Correlation analysis showed that TNF-α and IL-6 were negatively correlated with the prognosis of PCM, while IL-10 was positively correlated with the prognosis of PCM. ROC curve analysis showed that the areas under the curve for TNF-α, IL-6 and IL-10 to predict the prognosis of surgical treatment of PCM were 0.896, 0.931 and 0.709 respectively. Conclusions: The expression of immune factors such as TNF-α, IL-6 and IL-10 is closely related to the prognosis of surgical treatment of PCM, which has high predictive value for its prognosis.

Immunomodulatory Effects of a Prebiotic Formula with 2'-Fucosyllactose and Galacto- and Fructo-Oligosaccharides on Cyclophosphamide (CTX)-Induced Immunosuppressed BALB/c Mice via the Gut-Immune Axis.

Obejectives: This study explored the immunomodulatory effects of a prebiotic formula consisting of 2'-fucosyllactose (2'-FL), galacto-oligosaccharides (GOSs), and fructo-oligosaccharides (FOSs) (hereinafter referred to as 2FGF) in cyclophosphamide (CTX)-induced immunosuppressed BALB/c mice and its underlying mechanisms. Methods: Sixty healthy female BALB/c mice were randomly divided into the following groups: normal control (NC) group; CTX treatment (CTX) group; 2FGF low-dose (2FGF-L) group; 2FGF medium-dose (2FGF-M) group; and 2FGF high-dose (2FGF-H) group. An immunosuppressed model was established in the 2FGF-H group by intraperitoneal injection of 80 mg/kg CTX. After 30 days of 2FGF intervention, peripheral blood, spleen tissue, thymus tissue, and intestinal tissue from the mice were collected and analyzed. The changes in weight and food intake of the mice were recorded weekly. Hematoxylin-eosin (HE) staining was used to observe the histological change of the spleen tissue. Enzyme-linked immunosorbent assay (ELISA) was employed to detect cytokine levels in peripheral blood. Flow cytometry was used to analyze T lymphocyte subgroup ratio of splenic lymphocytes. Western blot analysis was conducted on intestinal tissues to assess the expression of proteins involved in the tight junction, toll-like receptor 4 (TLR4), mitogen-activated protein kinase (MAPK), and nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) signaling pathways. Additionally, molecular techniques were used to analyze the intestinal microbiota. Results: The results showed that 2FGF restored CTX-induced splenic injury, increased the number of splenic T lymphocytes, and elevated serum cytokines such as interleukin-4 (IL-4) and IL-10. In the intestine, 2FGF upregulated the expression of intestinal epithelial tight junction proteins such as Claudin-1 and zonula occludens 1 (ZO-1), thereby enhancing intestinal barrier function and activating the MAPK and NF-κB pathways via TLR4. Furthermore, 2FGF elevated the α-diversity (Shannon and Simpson indices) of the gut microbiota in CTX-induced immunosuppressed mice, enriching bacteria species positively correlated with anti-inflammatory cytokines (e.g., IL-4) such as g_Streptomyces and g_Bacillus and negatively correlated with pro-inflammatory cytokines (e.g., IL-1β) such as g_Saccharomyces. The results suggest that 2FGF may enhance immunity via the gut-immune axis. Conclusions: The 2FGF prebiotic formula showed an immunomodulatory effect in CTX-induced immunosuppressed mice, and the mechanism of which might involve optimizing the gut flora, enhancing intestinal homeostasis, strengthening the intestinal barrier, and promoting the expression of immune factors by regulating the TLR-4/MAPK/NF-κB pathway.

NQO1 from Litopenaeus vannamei involved in the regulation of antioxidant capacity, inflammation, and apoptosis

NAD(P)H:quinone oxidoreductase 1 (NQO1) is a versatile FAD-dependent flavoprotein and a key regulator in the Nrf2/ARE signaling pathway. In this study, we cloned the NQO1 gene of Litopenaeus vannamei (LvNQO1) and investigated its role in immune regulation. The results showed that the LvNQO1 gene has an ORF of 987 bp, encoding 328 amino acids. The protein contains an NQO family domain. Homology and phylogenetic analysis revealed that LvNQO1 shares similarities with the NQO1 of Marsupenaeus japonicus, clustering into the same clade. LvNQO1 was expressed in 10 tissues of L. vannamei, with the highest expression in the hepatopancreas and the lowest in the intestine. After RNA interference (RNAi) of LvNQO1, the expression of antioxidant genes (SOD and GST) initially increased but then decreased after 24 h. The expression levels of Gpx and CAT decreased early on but gradually recovered. Immune-related factors (Toll4, JNK, and Hsp90) and apoptosis-related factors (Caspase3, P53, and bcl2) were upregulated. Following RNAi of LvNQO1, Vibrio harveyi challenge significantly increased the expression of immune factors (JNK and HIF1α) and apoptosis factors (Caspase3, P53, and bcl2) in the hepatopancreas. Toll 4 receptors recognized the infection, upregulated their expression, and activated an immune response. RNAi of LvNQO1 led to noticeable histological lesions and apoptosis. These findings suggest that LvNQO1 may play a role in regulating antioxidant capacity, inflammation, and apoptosis in response to Vibrio infection.

Isolation and complete genome sequence analysis of Vibrio rotiferianus strain TO-01 from Trachinotus ovatus to reveal its pathogenicity and drug resistance

Vibrio rotiferianus is a pathogenic bacterium that is widely distributed in the ocean and can cause diseases in a variety of marine animals, including fish, shrimp and shellfish. In this study, we isolated and identified V. rotiferianus strain TO-01 from diseased Trachinotus ovatus. Infected fish exhibited a range of pathological symptoms, including lethargy in swimming, blackened body coloration, skin ulceration and erratic side swimming. Tissue section examination revealed pronounced damage to the liver, spleen and gills of the infected fish. An analysis of immune factor expression revealed a significant increase in the expression of inflammatory factors, including interleukin (IL)-1, IL-2, IL-6 receptor and IL-21, in the spleen and kidney of fish infected with TO-01 at 6 h post-infection. To gain a more in-depth comprehension of the pathogenicity and drug resistance of V. rotiferianus, we conducted whole genome sequencing. The total genome length of V. rotiferianus was 4734,075 bp, and 74 virulence factors were predicted within the genome. Most of these virulence genes were associated with bacterial adhesion and flagellar motility. A gene associated with group sensing, cqsA, and a gene associated with hemolysin, tlh, were also identified. The prediction of drug resistance genes was in agreement with the results of drug sensitivity assays, both of which indicated that TO-01 has significant resistance to β-lactams. The findings of this study significantly enhance our understanding of the pathogenic mechanism of V. rotiferianus and give crucial insights into disease prevention and control in the management of T. ovatus.

Integrating tumor and healthy epithelium in a micro-physiology multi-compartment approach to study renal cell carcinoma pathophysiology

The advent of micro-physiological systems (MPS) in biomedical research has enabled the introduction of more complex and relevant physiological into in vitro models. The recreation of complex morphological features in three-dimensional environments can recapitulate otherwise absent dynamic interactions in conventional models. In this study we developed an advanced in vitro Renal Cell Carcinoma (RCC) that mimics the interplay between healthy and malignant renal tissue. Based on the TissUse Humimic platform our model combines healthy renal proximal tubule epithelial cells (RPTEC) and RCC. Co-culturing reconstructed RPTEC tubules with RCC spheroids in a closed micro-perfused circuit resulted in significant phenotypical changes to the tubules. Expression of immune factors revealed that interleukin-8 (IL-8) and tumor necrosis factor-alfa (TNF-α) were upregulated in the non-malignant cells while neutrophil gelatinase-associated lipocalin (NGAL) was downregulated in both RCC and RPTEC. Metabolic analysis showed that RCC prompted a shift in the energy production of RPTEC tubules, inducing glycolysis, in a metabolic adaptation that likely supports RCC growth and immunogenicity. In contrast, RCC maintained stable metabolic activity, emphasizing their resilience to external factors. RNA-seq and biological process analysis of primary RTPTEC tubules demonstrated that the 3D tubular architecture and MPS conditions reverted cells to a predominant oxidative phosphorylate state, a departure from the glycolytic metabolism observed in 2D culture. This dynamic RCC co-culture model, approximates the physiology of healthy renal tubules to that of RCC, providing new insights into tumor-host interactions. Our approach can show that an RCC-MPS can expand the complexity and scope of pathophysiology and biomarker studies in kidney cancer research.

Pseudostellaria heterophylla improves intestinal microecology through modulating gut microbiota and metabolites in mice.

Pseudostellaria heterophylla is a Chinese medicine and healthy edible that is widely used to for its immunomodulatory, antioxidant, antidiabetic and antitussive properties. However, the potential function of P. heterophylla in intestinal microecology remains unclear. In this study, we investigated the impact of P. heterophylla on immune functions and evaluated its potential to regulate the gut microbiota and metabolome. The results showed that P. heterophylla significantly increased the content of red blood cells, total antioxidant capacity and expression of immune factors, and decreased platelet counts when compared to the control under cyclophosphamide injury. In addition, P. heterophylla altered the diversity and composition of the gut bacterial community; increased the abundance of potentially beneficial Akkermansia, Roseburia, unclassified Clostridiaceae, Mucispirillum, Anaeroplasma and Parabacteroides; and decreased the relative abundance of pathogenic Cupriavidus and Staphylococcus in healthy mice. Metabolomic analyses showed that P. heterophylla significantly increased the content of functional oligosaccharides, common oligosaccharides, vitamins and functional substances. Probiotics and pathogens were regulated by metabolites across 11 pathways in the bacterial-host co-metabolism network. We demonstrated that P. heterophylla increased the abundance of probiotics and decreased pathogens, and further stimulated host microbes to produce beneficial secondary metabolites for host health. Our studies highlight the role of P. heterophylla in gut health and provide new insights for the development of traditional Chinese medicine in the diet. © 2024 Society of Chemical Industry.

The Molecular Characterization of the Cyprinid herpesvirus 3 (CyHV-3) ORF24 Protein and its effect on the expression of immune genes (in vitro)

Cyprinid herpesvirus 3 (CyHV-3), known as koi herpesvirus (KHV), is highly contagious and lethal. In this study, we aimed to characterize the ORF24-encoding protein of CyHV-3, investigate its sub-cellular localization, and determine its impact on the expression of immune factors through in vitro experiments. The results showed that the CyHV-3 ORF24 protein comprises 579 amino acids. Interestingly, multiple comparisons with homologous proteins from three carp herpesvirus origins showed no significant similarity. The fluorescence localization experiment showed that the green fluorescence signal, representing the protein pEGFP-ORF24, was primarily diffused in the cytoplasm. Notably, the overexpression of ORF24 effectively suppressed the expression of immune factors in both CCO (Channel catfish ovary) and FHM (Fathead minnow muscle cell line) cells. Bioinformatic analysis indicated that the CyHV-3 ORF24 gene exhibited significant differences from the corresponding genes in the other two carp herpesviruses. This suggests its unique functional role in the evolutionary context. Moreover, our findings demonstrated that overexpression of CyHV-3 ORF24 can effectively inhibit the expression of immune factors, underscoring its crucial role as a viral immune escape factor. These results provide further insights into the immune function of the CyHV-3 ORF24 protein and offer a theoretical foundation for developing new vaccines against CyHV-3 virus infections.

Infection of domestic pigs with a genotype II potent strain of ASFV causes cytokine storm and lymphocyte mass reduction.

The whole-genome sequence of an African swine fever virus (ASFV) strain (HuB/HH/2019) isolated from Hubei, China, was highly similar to that of the Georgia 2007/1 strain ASFV. After infection with strong strains, domestic pigs show typical symptoms of infection, including fever, depression, reddening of the skin, hemorrhagic swelling of various tissues, and dysfunction. The earliest detoxification occurred in pharyngeal swabs at 4 days post-infection. The viral load in the blood was extremely high, and ASFV was detected in multiple tissues, with the highest viral loads in the spleen and lungs. An imbalance between pro- and anti-inflammatory factors in the serum leads to an excessive inflammatory response in the body. Immune factor expression is suppressed without effectively eliciting an immune defense. Antibodies against p30 were not detected in acutely dead domestic pigs. Sequencing of the peripheral blood mononuclear cell transcriptome revealed elevated transcription of genes associated with immunity, defense, and stress. The massive reduction in lymphocyte counts in the blood collapses the body's immune system. An excessive inflammatory response with a massive reduction in the lymphocyte count may be an important cause of mortality in domestic pigs. These two reasons have inspired researchers to reduce excessive inflammatory responses and stimulate effective immune responses for future vaccine development.

CuO nanoparticles elicit intestinal immunotoxicity in zebrafish based on intestinal microbiota dysbiosis.

Copper II oxide nanoparticles (CuO NPs), a kind of widely used nanomaterial, have been detected in food and the environment, which has aroused widespread public concern. Recently, increasing data have suggested that intestinal microecology is closely related to immune homeostasis. However, the intestinal immunotoxicity induced by CuO NPs through intestinal microbiota is still unknown. Therefore, in this study, zebrafish were exposed to CuO NPs to explore intestinal immunotoxicity by evaluating physiological indicators, intestinal tissue injury, antioxidant enzyme activities, gene expression of immune factors, and changes in intestinal microbiota and its metabolites (short-chain fatty acids (SCFAs) and lipopolysaccharides (LPS)). The results revealed that the intestinal immunotoxicity of CuO NPs was mediated by the impact on intestinal microbiota and its metabolite levels. Specifically, changes were observed in the abundance of microbes that participated in the metabolism of SCFAs and LPS. The reduction in acetic acid, propionic acid and valeric acid upregulated GPR84 expression, and the decline in LPS levels further resulted in the suppression of the key immune regulatory pathways TLR4/MyD88/NF-κB, ultimately leading to intestinal immunotoxicity. This study would provide a scientific basis for the risk assessment of CuO NPs and a new perspective for research on the immunotoxicity of nanoparticles.

Analysis of alternative splicing provides insights into its vital roles in immune responses of half-smooth tongue sole (Cynoglossus semilaevis) against Vibrio anguillarum

Aquaculture plays important roles in global food security. Prized as a valuable commercial species, the aquaculture industry of half-smooth tongue sole (Cynoglossus semilaevis) has faced unprecedented challenge due to bacterial diseases, including vibriosis caused by Vibrio anguillarum. Alternative splicing (AS) is an important layer of post-transcriptional regulation, being involved in almost all biological processes, including development, reproduction, and immunity. However, its roles in immunity in half-smooth tongue sole remain elusive. In this study, therefore, we profiled the changes of alternative splicing in half-smooth tongue sole after infection with different concentrations of V. anguillarum, and investigated their functions by both enrichment analysis and targeted gene transcript overexpression analysis with half-smooth tongue sole macrophages. Intriguingly, differentially alternatively spliced (DAS) genes were found to be involved in RNA splicing for each bacterial treatment and for the shared gene set, consistent with previous studies that splicing factor themselves often underwent alternative splicing. A set of 12 immune-related shared DAS genes were identified, including hp, c5, and traf2b. Targeted gene analysis using the shared DAS gene, haptoglobin (hp), showed that alternative splicing resulted in changes of protein domains, and overexpression analysis demonstrated that two transcripts of hp exhibited contrary roles in stimulating or reducing the expression of immune factors in response to lipopolysaccharides (LPS), reflecting the vital roles of alternative splicing in immunity of tongue sole. DAS events were further verified by qRT-PCR (20 primer pairs for 10 DAS events) to confirm the reliability of our bioinformatics analysis. This study, for the first time, revealed the involvement of alternative splicing in immune responses of half-smooth tongue sole using both omics data and targeted gene functional analysis, setting a solid foundation for further analysis and providing clues for potential usage in controlling bacterial diseases in aquaculture.

UHPLC-MS-Based Metabolomics Reveal the Potential Mechanism of Armillaria mellea Acid Polysaccharide in and Its Effects on Cyclophosphamide-Induced Immunosuppressed Mice.

Armillaria mellea (Vahl) P. Kumm is commonly used for food and pharmaceutical supplements due to its immune regulatory function, and polysaccharides are one of its main components. The aim of this research is to study the immunological activity of the purified acidic polysaccharide fraction, namely, AMPA, isolated from Armillaria mellea crude polysaccharide (AMP). In this study, a combination of the immune activity of mouse macrophages in vitro and serum metabonomics in vivo was used to comprehensively explore the cell viability and metabolic changes in immune-deficient mice in the AMPA intervention, with the aim of elucidating the potential mechanisms of AMPA in the treatment of immunodeficiency. The in vitro experiments revealed that, compared with LPS-induced RAW264.7, the AMPA treatment elevated the levels of the cellular immune factors IL-2, IL-6, IgM, IgA, TNF-α, and IFN-γ; promoted the expression of immune proteins; and activated the TLR4/MyD88/NF-κB signaling pathway to produce immunological responses. The protein expression was also demonstrated in the spleen of the cyclophosphamide immunosuppressive model in vivo. The UHPLC-MS-based metabolomic analysis revealed that AMPA significantly modulated six endogenous metabolites in mice, with the associated metabolic pathways of AMPA for treating immunodeficiency selected as potential therapeutic biomarkers. The results demonstrate that phosphorylated acetyl CoA, glycolysis, and the TCA cycle were mainly activated to enhance immune factor expression and provide immune protection to the body. These experimental results are important for the development and application of AMPA as a valuable health food or drug that enhances immunity.

Software for evaluation of immune cell activation (Application note)

Biological processes involving immune response exhibit nonlinearity due to complex interactions between different cells. The presented mathematical model considers the temporal development of immune reactions, and corresponding kinetic processes, including the interaction of cells/soluble immune factors in vitro. According to the M1/M2 paradigm of macrophage polarization, unbalanced macrophage activation in the human body can cause an excessive response to an antigen and associated long-term deleterious processes. Therefore, our simulation is based on the evaluation of parameters that describe the interaction of diverse immune factors interconnected within the framework of the M1/M2 paradigm, and taking into account the kinetics of expression of immune factors. A specific program and related web tool to assess the intensity of immune reactions in cell system in vitro were developed. AvailabilityIt is accessible through a web-link: https://www.biodevicesystems.com/immunology. ContactUsers can get information and apply for the service at info@biodevicesystems.com.

Study on toxicity responses and their mechanisms in Xenopus tropicalis long-term exposure to Shigella flexneri and ciprofloxacin

The abuse and overuse of antibiotics increased not only the exposure of aquatic animals to antibiotics but also the development of resistance in pathogenic bacteria. To investigate the effects and mechanisms of exposure, a long-term experiment lasting 120 days was conducted in which Xenopus tropicalis was exposed to single and combined stress factors of multiresistant pathogenic Shigella flexneri and ciprofloxacin (CIP). The intestinal oxidative stress, immune factors and flora, as well as the brain-gut axis correlation factors of X. tropicalis, were tracked to account for the response of aquatic animals to the exogenous pollutants. SOD activity and MDA content were significantly increased in stressed X. tropicalis (p < 0.001), while the levels of proinflammatory factors (IL-1β, IFN-γ) were significantly reduced (p < 0.01). The content of intestinal beneficial bacteria decreased and that of harmful bacteria increased in the intestinal flora of the stressed X. tropicalis (p < 0.001). These results suggested that S. flexneri and CIP disturbed the intestinal flora and caused oxidative damage in the host, and the body produced a series of responses, such as oxidative stress responses and regulation of the expression of immune factors, to maintain the balance of antioxidant inflammation. Significant changes in the expression of intestinal neurotransmitters (5-HT, CGRP) and brain peptides (BDNF, NCAM, NPY) (p < 0.05) also indicated that the brain-gut axis interaction was disrupted. In addition, although the coexisting CIP could reduce intestinal toxicity caused by S. flexneri, the amount of intestinal pathogenic bacteria Desulfovibrio increased significantly. Moreover, compared with the single exposure group, SOD activity, CAT activity and MDA content were significantly reduced in the dual exposure group. Therefore, the health risks of multiresistant pathogenic bacteria on the intestinal and brain-gut axis interaction should be given more attention, and the interaction of brain-gut axis is more important when antibiotics coexist.

Identification and functional analysis of endoplasmic reticulum oxidoreductase 1 (ERO1) from the green mud crab Scylla paramamosain: The first evidence of ERO1 involved in invertebrate immune response.

Endoplasmic reticulum oxidoreductase 1 (ERO1) is an important mediator in regulating disulfide bond formation and maintaining endoplasmic reticulum homeostasis. Its activity is transcriptionally regulated by the unfolded protein response (UPR) in the endoplasmic reticulum, which is known to be essential in immunity. However, whether ERO1 is involved in innate immunity in invertebrates remains unclear. In the present study, two subtypes of ERO1 from Scylla paramamosain were first identified and characterized. Sequence analysis revealed the conserved ERO1 domain and the oxidative capacity assay verified the oxidative capacity of SpERO1 recombinant protein. Moreover, SpERO1s were found to be ubiquitously expressed in all the tested tissues, with the highest expression observed in hemocytes. Two SpERO1s exhibited distinct expression patterns in response to Vibrio alginolyticus and White Spot Syndrome Virus (WSSV). Importantly, the downregulation of the expression of immune factors upon bacterial challenge in SpERO1-silenced crabs was observed. These results provided an initial foundation for further investigations into the role of ERO1 in the innate immunity of invertebrates.

IFN1 Enhances Thrombocyte Phagocytosis through IFN Receptor Complex-JAK/STAT-Complement C3.3-CR1 Pathway and Facilitates Antibacterial Immune Regulation in Teleost.

Type I IFNs with strong positive charges exhibit robust bactericidal activity and a protective effect against bacterial infections. However, the antibacterial mechanism invivo remains unknown. In this study, Ab blockade of IFN1, a member of type I IFNs in grass carp (Ctenopharyngodon idella), resulted in high mortality, tissue bacterial loads, and low expression of immune factors after bacterial challenge, which indicates that the antibacterial activity of IFN1 has physiological significance. Meanwhile, we injected grass carp with the recombinant and purified intact IFN1 protein after bacterial injection, and the result demonstrated a remarkable therapeutic effect. Furthermore, we found that IFN1 expression was remarkably induced in blood cells after bacterial challenge, and prophagocytosis via IFN1 mostly increased in thrombocytes. Then, we isolated peripheral blood thrombocytes by polyclonal Ab of CD41 and stimulated thrombocytes with recombinant IFN1, and the results indicated that immune factors and complement components (especially C3.3) were induced. Unexpectedly, complements demonstrated not only bacteriolysis but also bacterial aggregation. Furthermore, Ab blockades of the three subunits (CRFB1/CRFB2/CRFB5) of the IFN1 receptor or inhibition of STAT1 almost abolished the prophagocytosis via IFN1 and reduced C3.3 and immune factor expression in thrombocytes. Meanwhile, Ab blockade of the complement receptor CR1 greatly attenuated the prophagocytosis of IFN1. In contrast, mouse IFN-β did not show the promotion of antibacterial activity. These results clarify the prophagocytosis and immune regulation pathways of IFN1 in antibacterial immunity in teleosts. This study reveals the antibacterial mechanisms of type I IFNs invivo and inspires functional studies of IFN in bacterial infections.

Tebuconazole mediates cognitive impairment via the microbe-gut-brain axis (MGBA) in mice

Tebuconazole, one of the most widely used triazole fungicides, is reported to potentially pose a risk of inducing neurological disorders in human beings. Considering the increasing exposure, whether it could influence cognitive function remains to be elucidated. Herein, we used a mouse model to evaluate the potential cognitive risks and possible mechanisms from the continuous edible application of tebuconazole at low concentrations. Our study revealed that tebuconazole deteriorated spatial learning and memory and downregulated the expression of glutamate receptor subunits. Importantly, metagenomic analysis indicated that tebuconazole not only led to significant shifts in the composition and diversity of the gut microbiota but also changed intestinal homeostasis. Specifically, after exposure, tebuconazole circulated in the bloodstream and largely entered the gut–brain axis for disruption, including disturbing the Firmicutes/Bacteroidetes ratio, interrelated neurotransmitters and systemic immune factors. Moreover, pretreatment with probiotics improved immune factor expression and restored the deterioration of synaptic function and spatial learning and memory. The current study provides novel insights concerning perturbations of the gut microbiome and its functions as a potential new mechanism by which tebuconazole exposes cognitive function-related human health.

Retracted: Effects of Acupuncture Combined with Exercise on Expression of Immune Factors in Aging Rats and Its Significance in Antiaging Intervention.

[This retracts the article DOI: 10.1155/2022/6833196.].

Limosilactobacillus fermentum-fermented ginseng improved antibiotic-induced diarrhoea and the gut microbiota profiles of rats.

This study investigated the efficacy of Limosilactobacillus fermentum-fermented ginseng for improving colitis and the gut microbiota profiles in rats and explored the benefits of the L.fermentum fermentation process to ginseng. Ginseng polysaccharide and ginsenoside from fermented ginseng were analysed by UV and HPLC. Antibiotic-fed rats were treated with fermented ginseng and a L.fermentum-ginseng mixture. Histopathology- and immune-related factors (TNF-α, IL-1β, IL-6 and IL-10) of the colon were assayed by using pathological sections and ELISA. After treatment, fermented ginseng relieved the symptoms of antibiotic-induced diarrhoea and colon inflammation, and the expression of colon immune factors returned to normal. The gut microbial communities were identified by 16S rRNA gene sequencing. The results showed that the alterations in the gut microbiota returned to normal. In addition, the gut microbiota changes were correlated with immune factor expression after treatment. The fermented ginseng had better biological functions than a L.fermentum-ginseng mixture. Fermented ginseng can relieve diarrhoea and colon inflammation and restore the gut microbiota to its original state. The process of L.fermentum fermentation can expand the therapeutic use of ginseng. This research suggested the potential function of fermented ginseng to relieve diarrhoea and recover the gut microbiota to a normal level and explored the benefits of the Limosilactobacillus fermentum fermentation process to ginseng.

Tannic acid antagonizes atrazine exposure-induced autophagy and DNA damage crosstalk in grass carp hepatocytes via NO/iNOS/NF-κB signaling pathway to maintain stable immune function

Atrazine (ATR) is a herbicide widely used in grass crops. The pollution of the soil and water environment is extremely harmful to aquatic animals and their offspring. iNOS/NO upregulation, DNA damage and cellular autophagy affect the immune function of fish liver cells. The effects of ATR at exposure doses on grass carp hepatocytes in terms of autophagy and DNA damage effects in genotoxicity, as well as the antagonistic effects of TAN on the above phenotypes and the internal mechanisms are not known. Therefore, we constructed control (Con group), ATR exposure (ATR group), TAN exposure (TAN group) and mixed group (ATR + TAN group) models on grass carp hepatocytes. Validation was performed by comet assay, MDC staining, qRT-PCR and protein blotting assay as well as iNOS/NO indicator levels and expression of immune factors as these experimental methods. Our data indicate that iNOS/NO assay kit measured that ATR treatment resulted in a significant increase in iNOS/NO activity and levels in grass carp hepatocytes (p < 0.05). We also found that NO/iNOS/NF-κB pathway genes were significantly activated (p < 0.05) at the exposure dose of ATR (3 μg mL−1). In addition, the proportion of cells that died due to DNA damage, autophagy, and immunotoxic effects was significantly increased at the exposure dose of ATR. Comet assay protein blotting detected increased DNA damage in cells at the ATR exposure dose (p < 0.05). MDC staining and qRT-PCR and protein blotting to detect the proportion of autophagic cells and autophagy-related genes also appeared upregulated at the exposed dose of ATR (p < 0.05). In brief, this study showed that ATR exposure caused cellular DNA damage and autophagy via the NO/iNOS/NF-κB axis, which led to immunotoxic effects and eventual death of grass carp hepatocytes. The present study facilitates the demonstration of the molecular mechanism of TAN alleviation of ATR cytotoxicity from the perspective of NO-mediated iNOS/NF-κB axis. It provides insights into the protection of farmed fish from agricultural contaminants and opens up new horizons in the use of natural plant-derived monomers for the clinical treatment of antagonistic triazine pesticide poisoning.