Expression Of IL-1β Research Articles

Effect of leptin and adiponectin on the expression of cytokine genes IL-1β, IL-6 AND TNFα in lymphocytes

Metabolic syndrome (MS) is one of the world’s topical health problems. Large-scale epidemiological studies on the prevalence of MS in the world have not been conducted, but according to different authors, depending on the region of residence, the composition of the study population and the diagnostic criteria used, the incidence of MS is at least 10%, and according to estimates of the International Diabetes Federation IDF – up to 25% of the adult population. The metabolic changes in MS are explained by a disturbance in the balance of mediators synthesized by adipose tissue (adiponectin, leptin, resistin, visfatin, vaspin and others); MS is also considered as a subclinical chronic inflammatory process characterized by excessive synthesis of proinflammatory and deficiency of anti-inflammatory cytokines. According to modern ideas, changes in the cellular and humoral immunity in MS are largely due to the imbalance of adipokines: leptin and adiponectin. Increased functional activity of immune cells, including lymphocytes, leads to changes in cytokine gene expression. In the present work, we studied in vitro the expression of IL-1â, IL-6 and TNFá genes in peripheral blood lymphocytes under the influence of adipokines at concentrations characteristic of MS. As a result, differential effects of adipokines on lymphocytes of MS patients and conditionally healthy individuals were found. In conditionally healthy individuals, incubation of lymphocytes with adipokines leptin, adiponectin and their combination, as well as in the presence of physiological solution causes an increase in IL-6 gene expression. The most noticeable effect was observed when cultured with adiponectin. Thus, in norm, with a decrease in the physiological concentration of adiponectin, the expression of IL-6 in lymphocytes increases, indicating insufficient realization of the anti-inflammatory effect of adiponectin. In MS, IL-6 gene expression increases in lymphocytes isolated from peripheral blood in vitro after incubation with adiponectin, a combination of adiponectin and leptin, as well as in the presence of physiological solution. No changes in IL-6 gene expression under the effect of high concentration of leptin were detected. Probably, our results reflect the phenomenon of lymphocyte resistance to leptin action in MS, as under its influence there is not activation of lymphocytes characteristic in vivo, but on the contrary, decrease of activated subpopulations, also there is no change in IL-6 gene expression. Thus, adipokines in concentrations characteristic of metabolic syndrome influence the functional activity of peripheral blood lymphocytes.

Comparison of the effect of anticoccidial drug, probiotic, synbiotic, phytochemicals and vaccine in prevention and control of coccidiosis in broiler chickens challenged with Eimeria spp

The objective of this study was to investigate the effects of an anti-coccidiosis drug, vaccine, probiotic, symbiotic, and phytochemicals in the prevention and control of coccidia infection in broilers. A total of 525 one-day-old Ross 308 chicks were randomly allocated to 7 experimental diets with 5 replicates of 15 birds each in a completely randomized design. Experimental diets consisted of negative control (NC) without any additives and not challenged. The other 6 groups were challenged with mixed Eimeria and fed the basal diet with no additives (Positive Control, PC) or supplemented with Coxidine 100 (1 g / 1 kg), probiotic, synbiotic, Livacox T vaccine and phytobiotic additives based on the manufacturer's recommended dose. Body weight gain (WG), feed intake (FI) and feed conversion ratio (FCR) were recorded weekly. Oocysts per gram of excreta (OPG) were determined on d 25 to 33 and 42. One bird per cage was euthanized to analyze lesion score and jejunum and ileum inflammatory genes expression. Coccidial challenge reduced WG (P < 0.05) during 15 to 28 d and vaccine treatment was more effective in improving WG and FCR on d 29 to 42 and 1 to 42 (P < 0.05) than other treatments. Birds in the PC group had higher (P < 0.05) OPG than NC group for all days and the vaccine treatment resulted in the lowest rate of OPG compared to other treatments (P < 0.05) at 27, 28, 29, 30, 32, and 33 d of age and overall average. Relative mRNA levels of IFN-γ, IL-1β and IL-10 were significantly upregulated among treatments under coccidiosis challenge in jejunum and ileum except for IL-1β expression in the ileum. In conclusion, based on the results of this study the individual characteristics of feed additives for the prevention of coccidiosis can be different depending on the type and source of feed additives, duration, and amount used, levels of oocyst inoculation and Eimeria types.

Blockage of ATGL-mediated breakdown of lipid droplets in microglia alleviates neuroinflammatory and behavioural responses to lipopolysaccharides

Lipid droplets (LD) are triglyceride storing organelles that have emerged as an important component of cellular inflammatory responses. LD lipolysis via adipose triglyceride lipase (ATGL), the enzyme that catalyses the rate-limiting step of triglyceride lipolysis, regulates inflammation in peripheral immune and non-immune cells. ATGL elicits both pro- and anti-inflammatory responses in the periphery in a cell-type dependent manner. The present study determined the impact of ATGL inhibition and microglia-specific ATGL genetic loss-of-function on acute inflammatory and behavioural responses to pro-inflammatory insult. First, we evaluated the impact of lipolysis inhibition on lipopolysaccharide (LPS)-induced expression and secretion of cytokines and phagocytosis in mouse primary microglia cultures. Lipase inhibitors (ORlistat and ATGListatin) and LPS led to LD accumulation in microglia. Pan-lipase inhibition with ORlistat alleviated LPS-induced expression of IL-1β and IL-6. Specific inhibition of ATGL had a similar action on CCL2, IL-1β and IL-6 expression in both neonatal and adult microglia cultures. CCL2 and IL-6 secretion were also reduced by ATGListatin or knockdown of ATGL. ATGListatin increased phagocytosis in neonatal cultures independently from LPS treatment. Second, targeted and untargeted lipid profiling revealed that ATGListatin reduced LPS-induced generation of pro-inflammatory prostanoids and modulated ceramide species in neonatal microglia. Finally, the role of microglial ATGL in neuroinflammation was assessed using a novel microglia-specific and inducible ATGL knockout mouse model. Loss of microglial ATGL in adult male mice dampened LPS-induced expression of IL-6 and IL-1β and microglial density. LPS-induced sickness- and anxiety-like behaviours were also reduced in male mice with loss of ATGL in microglia. Together, our results demonstrate potent anti-inflammatory effects produced by pharmacological or genetic inhibition of ATGL-mediated triglyceride lipolysis and thereby propose that supressing microglial LD lipolysis has beneficial actions in acute neuroinflammatory conditions.

ZNF429 Participates in the Progression of Coronary Heart Disease through Regulating Inflammatory and Adhesive Factors

Background: Coronary heart disease (CHD) is an intricate and multifaceted cardiovascular disorder that contributes significantly to global morbidity and mortality. Early and accurate identification and diagnosis of CHD are paramount to ensuring patients receive optimal therapeutic interventions and satisfactory outcomes. Methods: Data on CHD gene expression were obtained from the Gene Expression Omnibus (GEO) repository and potential hub genes were screened through gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), weighted gene co-expression network analysis (WGCNA), and least absolute shrinkage and selection operator (LASSO) analyses. Functional validation of these hub genes was conducted by interfering with them in human umbilical vein endothelial cells (HUVECs). Cell proliferation and apoptosis were assessed through cell counting kit-8 (CCK-8) and flow cytometry assays, respectively, while enzyme-linked immunosorbent assay (ELISA), quantitative polymerase chain reaction (qPCR), Western blot, and immunofluorescence were used to measure the expression of key indicators. Results: We identified 700 upregulated differentially expressed genes (DEGs) and 638 downregulated DEGs in CHD, and utilized LASSO analyses to screen disease potential biomarkers, such as zinc finger protein 429 (ZNF429). Interference with ZNF429 in HUVECs mitigated the CHD-induced decrease in cell proliferation and increase in apoptosis. Moreover, the expression of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), cluster of differentiation 62E (CD62E), and cluster of differentiation 62P (CD62P) was reduced, leading to decreased cellular inflammation and adhesion. Conclusions: CHD-associated biomarker ZNF429 was identified through bioinformatics analysis to potentially regulate the expression of inflammatory factors IL-6, IL-1β, and TNF-α, along with adhesion molecules ICAM-1, VCAM-1, CD62E, and CD62P. This modulation influence was subsequently found to impact the progression of CHD. These findings offered valuable insights into potential targets for further investigation and therapeutic interventions for CHD management.

New Insights into the Structure-Activity Relationship of a Novel Immunomodulatory Peptide (HPHPHLSF) from Casein Hydrolyzed by Kluyveromyces marxianus JY-1: Molecular Docking, Interaction Evaluation, and HOMO Analysis.

Casein is rich in immunomodulatory peptides. In this study, the release of casein-derived immunomodulatory peptides by Kluyveromyces marxianus JY-1 was investigated for the first time, and an immunosuppressive mouse model was used to evaluate the immunomodulatory activity in the casein hydrolysate. The results showed that the cellular and humoral immunity of immunosuppressed mice could be significantly enhanced by casein hydrolysate. Peptide HPHPHLSF with high immunomodulatory activity from casein hydrolysate was screened using the virtual screening technique. HPHPHLSF possessed strong immunomodulatory activity and significantly upregulated the expression of IL-6, IL-1β, and TNF-α. Next, the interaction of HPHPHLSF with TLR2/4 on the cell surface of RAW264.7 cells was further elucidated by molecular docking and combined analysis of double-stranded small interfering RNA and receptor inhibitors. Further, the results of the highest occupied molecular orbital energy distribution elucidated that the histidine active site C48═O49 played an important role in the immunomodulatory activity of HPHPHLSF. This study confirmed that casein hydrolyzed by K. marxianus JY-1 was a natural immunomodulator, while the structure-activity relationship analysis provided new theoretical and technical support for the targeted preparation and screening of casein-derived immunomodulatory peptides.

Activation of GABABR Attenuates Intestinal Inflammation by Reducing Oxidative Stress through Modulating the TLR4/MyD88/NLRP3 Pathway and Gut Microbiota Abundance.

Oxidative stress emerges as a prominent factor in the onset and progression of intestinal inflammation, primarily due to its critical role in damaging cells and tissues. GABAergic signaling is important in the occurrence and development of various intestinal disorders, yet its effect on oxidative stress remains unclear. We attempted to assess whether GABAergic signaling participated in the regulation of oxidative stress during enteritis. The results showed that lipopolysaccharide (LPS) significantly decreased γ-aminobutyric acid (GABA) levels in the ileal tissues of mice. Interestingly, the application of GABA significantly repressed the shedding of intestinal mucosal epithelial cells and inflammatory cell infiltration, inhibited the expressions of proinflammatory factors, including granulocyte colony-stimulating factor and granulocyte-macrophage colony stimulating factor, and enhanced the levels of anti-inflammatory cytokines interleukin (IL)-4 and IL-10, indicating that GABA could alleviate enteritis in mice. This observation was further supported by transcriptome sequencing, revealing a total of 271 differentially expressed genes, which exhibited a marked enrichment of inflammatory and immune-related pathways, alongside a prominent enhancement of GABA B receptor (GABABR) signaling following GABA administration. Effectively, Baclofen pretreatment alleviated intestinal mucosal damage in LPS-induced mice, suppressed proinflammatory cytokines IL-1β, IL-6, and tumor necrosis factor alpha expressions, and boosted total antioxidant capacity, superoxide dismutase (SOD), and glutathione (GSH) levels. Moreover, Baclofen notably enhanced the viability of LPS-stimulated IPEC-J2 cells, contracted the proinflammatory secretion factors, and reinforced SOD, GSH, and catalase levels, emphasizing the anti-inflammatory and antioxidant effects associated with GABABR activation. Mechanistically, Baclofen restrained the mRNA and protein levels of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 3 (NLRP3), and inducible nitric oxide synthase, while elevating nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 in both mice and IPEC-J2 cells, indicating that activating GABABR strengthened antioxidant abilities by interrupting the TLR4/MyD88/NLRP3 pathway. Furthermore, 16S rDNA analysis demonstrated that Baclofen increased the relative abundance of probiotic, particularly Lactobacillus, renowned for its antioxidant properties, while reducing the relative richness of harmful bacteria, predominantly Enterobacteriaceae, suggesting that GABABR signaling may have contributed to reversing intestinal flora imbalances to relieve oxidative stress in LPS-induced mice. Our study identified previously unappreciated roles for GABABR signaling in constricting oxidative stress to attenuate enteritis, thus offering novel insights for the treatment of intestinal inflammation.

Increased expression of IL-1β in adipose tissue in obesity influences the development of colon cancer by promoting inflammation

Increased expression of IL-1β in adipose tissue in obesity influences the development of colon cancer by promoting inflammation

Gastrodin improves microglia-mediated inflammatory response after hypoxic-ischemic brain damage in neonatal rats via PI3K/AKT pathway

To investigate the mechanism of gastrodin for inhibiting microglia-mediated inflammation after hypoxicischemic brain damage (HIBD) in neonatal rats. Thirty-nine 3-day-old SD rats were randomly divided into sham group, HIBD group and gastrodin treatment group. Western blotting was used to detect the expressions of TNF-α, IL-1β, IL-10 and TGF- β1 in the corpus callosum of the rats. The potential targets of gastrodin for treatment of HIBD were screened by network pharmacology analysis. The expressions of PI3K/AKT signaling pathway proteins following HIBD-induced microglial activation in the rats and in cultured microglial BV-2 cells with oxygen-glucose deprivation (OGD) were detected with Western blotting. The effects of LY294002 (a specific inhibitor of the PI3K/AKT pathway) and gastrodin on TNF-α and TGF-β1 mRNA levels in BV-2 cells with OGD was detected with RT-qPCR. In the neonatal rats with HIBD, gastrodin treatment significantly decreased TNF-α and IL-1β expressions and enhanced IL-10 and TGF-β1 expressions in the ischemic corpus callosum. Network pharmacology analysis showed significant enrichment of the PI3K/AKT signaling pathway and a strong binding between gastrodin and PI3K. Gastrodin significantly promoted PI3K and AKT phosphorylation in neonatal rats with HIBD and in BV-2 cells exposed to OGD. In BV-2 cells with OGD, gastrodin obviously suppressed OGD-induced increase of TNF-α and reduction of TGF-β1 mRNA expressions, and this effect was strongly attenuated by LY294002 treatment. Gastrodin can inhibit microglia-mediated inflammation in neonatal rats with HIBD by regulating the PI3K/AKT signaling pathway.

CKAP2 Regulated by TFDP1 Promotes Metastasis and Proliferation of Colorectal Cancer through Affecting the Tumor Microenvironment.

The current pathological and physiological evaluation system for colorectal cancer (CRC) is limited; thus, effective biological targets to diagnose and treat this disease are urgently needed. In this study, we used qRT-PCR for detecting mRNA levels of genes. The levels of protein were identified by western blot, immunohistochemistry, and immunofluorescence assays. In addition, functional experiments were used to evaluate the role of CKAP2 in CRC cells and HUVECs. Bioinformatics analysis was employed to predict the binding relationship of CKAP2 and TFDP1, which was confirmed through dual luciferase reporter assay and immunoprecipitation assay. Furthermore, we injected HCT116 cells into mice flanks, and we injected Luciferase-labeled HCT116 cells into mice tail vein. HE staining was used to detect tumor nodules. As a result, high CKAP2 expression was found in CRC cells and tissues. CKAP2 silencing reduced CRC cell migration, invasion, proliferation, and epithelial-mesenchymal transition. Moreover, CKAP2 expression was positively associated with M2 macrophage level. CKAP2 promoted protein expression of CD86, CD206, IL-1β, and CCL17. Moreover, CKAP2 promoted the proliferation of HUVECs and angiogenesis via affecting the tumor microenvironment (TME). We also found that CKAP2 could interact with TFDP1. The inhibitory impacts of TFDP1 downregulation on CRC cell' proliferation, migration, and invasion were reversed via CKAP2 overexpression. In vivo silencing of CKAP2 repressed tumor growth and metastasis. Overall, CKAP2 was positively regulated by TFDP1, which promoted tumorigenesis and metastasis in CRC.

Primary Sjogren's Syndrome Associated with Lung Adenocarcinoma: Probing the Potential Common Pathogenic Mechanisms and Experimental Verification.

This study aimed to probe the potential common pathogenic mechanisms linking primary Sjogren's syndrome (pSS) and lung adenocarcinoma (LUAD) through bioinformatics analysis and experimental verification. The relevant genes associated with pSS and LUAD were retrieved from the Gene Expression Omnibus (GEO) database and Genecard database. Subsequently, differentially expressed genes (DEGs) associated with pSS and LUAD were screened as pSS-LUAD-DEGs. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses were performed to elucidate the significant biological functions of pSS-LUAD-DEGs. Core targets were identified by constructing the protein-protein interaction (PPI) network, further assessing hub gene diagnostic accuracy through Receiver Operating Characteristic (ROC) curve analyses. In this study, NOD/Ltj mice served as pSS animal models and were stimulated with particulate matter 2.5 (PM2.5) to generate an inflammatory reaction. Quantitative real-time polymerase chain reaction (qPCR), enzyme-linked immunosorbent assay (ELISA), and western blotting were employed for relevant molecular biology experiment verification. The results revealed through KEGG and GO enrichment analyses indicate that inflammation plays a critical role in linking pSS and LUAD. IL6, CCNA2, JAK2, IL1B, ASPM, CCNB2, NUSAP1, and CEP55 were determined as key targets of pSS-LUAD. BALB/c mice and NOD/Ltj mice exhibited enhanced expression of inflammatory cytokines IL-6 and IL-1β in lung tissues following 21 days of stimulation with PM2.5, activating the JAK2/STAT3 signaling pathway and up-regulating the expression of tumor-associated genes CCNA2, CCNB2, and CEP55, with NOD/Ltj mice exhibiting more pronounced changes than BALB/c mice. This protocol demonstrates that carcinogenesis induced by the pulmonary inflammatory microenvironment may be a key reason for the high incidence of LUAD in pSS patients. Additionally, blocking-related mechanisms may help prevent the occurrence of LUAD in pSS patients.

Curcumin alleviates septic lung injury in mice by inhibiting TXNIP/TRX-1/GPX4-mediated ferroptosis

To investigate whether curcumin alleviates septic lung injury by inhibiting ferroptosis through modulating the TXNIP/TRX-1/GPX4 pathway. Male C57BL/6 mice were randomly divided into Sham group, cecal ligation puncture (CLP)-induced sepsis group, CLP with curcumin treatment (50, 100, and 200 mg/kg) groups, and CLP with both curcumin (200 mg/kg) and TRX-1 inhibitor PX-12 (25 mg/kg) treatment group. Inflammatory factors, MDA, MPO, and GSH levels in the lung tissue of the mice were detected. Beas-2B cells stimulated with lipopolysaccharide (LPS; 1 μg/mL) were treated with 2.5, 5, or 10 μmol/L curcumin or with 10 μmol/L curcumin combined with 5 μmol/L PX-12, and the changes in MDA, Fe2+ and ROS levels were assessed. Western blotting was performed to detect the protein expressions of TXNIP, TRX-1, GPX4 and X-CT in both the mouse lung tissues and Beas-2B cells. The mice with CLP-induced sepsis showed severe lung injury with elevated expressions of IL-6, IL-1β, TNF-α, MDA and MPO and decreased GSH expression. In Beas-2B cells, LPS stimulation significantly increased MDA and Fe2+ levels and ROS release, increased TXNIP protein expression, and lowered the protein expression levels of TRX-1, GPX4 and X-CT, and these changes were also observed in the septic mice. Curcumin treatments at different concentrations obviously alleviated lung injury in the septic mice and reduced LPS-induced injury in Beas-2B cells. Curcumin significantly decreased the release of inflammatory factors, MDA and MPO, increased GSH level, lowered Fe2+, MDA and ROS levels, increased TXNIP protein expression, and lowered the protein expressions of TRX-1, GPX4 and X-CT in both septic mouse lung tissues and LPS-stimulated Beas-2B cells. The protective effect of curcumin was effectively blocked by PX-12 treatment. Curcumin inhibits ferroptosis and alleviates septic lung injury in mice by elevating TRX-1 and GPX4 and decreasing TXNIP in the lung tissue.

High temperature induces oxidative stress in spotted seabass (Lateolabrax maculatus) and leads to inflammation and apoptosis

Our study aims to examine the changes of long-term high temperature on the mortality and health status of spotted seabass (Lateolabrax maculatus), as well as to screen suitable biomarkers to determine whether the spotted seabass is under heat stress. In this study, 360 juvenile spotted seabass were evenly distributed into three temperature-controlled systems at 27 °C (N, normal temperature), 31 °C (M, moderate temperature), and 35 °C (H, high temperature) for an 8-week aquaculture experiment. The results revealed that 35 °C water temperature significantly increased the mortality and the MDA content in tissues (P < 0.05). Meanwhile, 35 °C water temperature significantly increased the activity of SOD enzyme and T-AOC capacity in tissues, as well as the expression of hsp60, hsp70, and hsp90 (P < 0.05). Additionally, the expression of nrf2, il1β, il8, caspase3, caspase9, and bax in the liver significantly increased (P < 0.05), while the expression of keap1, il10, tgfβ, and bcl2 decreased significantly (P < 0.05). These results indicate that 35 °C water temperature induces oxidative stress in spotted seabass, leading to tissue oxidative damage, promoting inflammation and apoptosis in liver, and increasing mortality. However, the organism compensates by heightening its antioxidant capacity via the Nrf2-Keap1 signaling pathway and inducing high expression of heat shock proteins for self-protection. Furthermore, the alterations in the mRNA level of hsp70 and MDA content in the liver, muscle, and kidney can serve as indicators for evaluating spotted seabass under prolonged heat stress.

Avanafil Mitigates Testicular Ischemia/Reperfusion Injury via NLRP3 Pathway Modulation in Rats.

In our study, the effectiveness of avanafil, a second-generation phosphodiesterase-5 (PDE5) inhibitor, on testicular torsion (TT) related ischemia/reperfusion injury via NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3), which triggers inflammatory response, are studied molecularly, biochemically and histopathologically. This study was performed on 24 male Wistar albino rats randomized into four groups. Testicular ischemia/reperfusion (I/R) model was created for groups 2, 3 and 4. Groups 3 and 4, respectively, were administered a dose of 5 and 10mg/kg avanafil before reperfusion by gavage. The testicles which were left in ischemia for two hours, were detorsioned for four hours. All animals were sacrificed after reperfusion. Testicular tissues were examined molecularly, biochemically and histopathologically. The NLRP3, Interleukin-1β (IL-1β) and Tumor Necrosis alpha (TNF-α) mRNA expression levels were observed to be significantly increased in the I/R group compared to the healthy group (p < 0.001). After both doses of avanafil, NLRP3, IL-1β and TNF-α mRNA expression levels, which increased as a result of I/R, decreased in both avanafil groups. (p < 0.001). The greatest decrease was seen at the dose of 10mg/kg (p < 0.001). Increased Malondialdehyde (MDA) levels due to I/R were statistically significantly decreased in both doses of avanafil (p < 0.001). Decreased Superoxide Dismutase (SOD) levels due to I/R damage increased statistically significantly in both doses of avanafil (p < 0.001). It was found that avanafil can reduce the damage caused by testicular I/R and that it will find new applications in the future with the support of advanced experimental and clinical studies.

Effects of propolis extract administration on immune parameters, faecal consistency scores, and growth performance of Holstein-Friesian calves.

The purpose of the study was to investigate the effect of Ethanolic Extract of Propolis (EEP) administration on immune parameters, faecal consistency scores, growth performance, and feed efficiency of Holstein Friesian calves. A total of 24 calves were divided into two different groups, control (n = 12) and EEP (n = 12). Both groups consisted of 6 male and 6 female calves. The calves were fed milk amounting to 10% of their birth weight each day until they reached 60days of age. Additionally, they were given starter feed and dry hay once a day. Calves assigned to the EEP group received 4ml of EEP daily. Use of EEP increased (P < 0.05) the serum IgG and IgM levels at 2months of age compared to the control group. EEP also showed efficacy (P < 0.01) in reducing faecal consistency in calves throughout the study. The levels of IL-1β, IL-6, TNF-α and NF-κB expression in calves treated with EEP were lower (P < 0.05) throughout the EEP application period. On the other hand, IGF-1 mRNA transcript levels were (P < 0.01) higher in EEP group calves than in the control group. Furthermore, EEP-fed calves consumed less dry matter for 1kg of live weight gain during the weaning-4months (P < 0.01) and birth-4months (P < 0.05) periods. These results indicate that EEP supplementation, through its immunostimulatory effects, plays a crucial role in the control of neonatal calf diarrhoea. Growth and development as well as IGF-1, which stimulates growth in almost all somatic cells, was also significantly increased by EEP supplementation. The combined effect of the rich bioactive compounds found in EEP appears to have a significant impact on health and well-being, resulting in improved early life performance in dairy calves.

EGCG alleviates Ochratoxin A-induced pyroptosis in rat's kidney by inhibiting NLRP3/Caspase-1/GSDMD signaling pathway

Ochratoxin A (OTA) exposure is inevitable due to its contamination in foods, and there is no treatment for the OTA induced organ toxicity. We evaluate the effect of epigallocatechin gallate (EGCG) on the nephrotoxicity caused by OTA, and to reveal the relationship of this effect with the NLRP3/Caspase-1/GSDMD pathway dependent pyroptosis. 40 male Wistar albino rats divided into 5 groups (n = 8, per group) 0.5 mg/kg/day OTA were administered to the rats and 50 mg/kg and 100 mg/kg EGCG were administered to the groups by gavage orally for 14 days. Serum urea and creatinine levels increased significantly with OTA exposure. Similarly, it was determined that significant changes in oxidative stress parameters with OTA exposure in kidney tissue. Also, there was a significant increase in kidney tissue TGF-β, NF-κB, IL-1β, IL-18, NLRP3, Caspase-1 and GSDMD mRNA expressions with OTA exposure. EGCG administration augmented a dose-dependent decrease in the aforementioned parameters. NLRP3/Caspase-1/GSDMD pathway is induced in the kidneys due to OTA exposure were shown with this study. Potent antioxidant EGCG could alleviate the pathways specified with this study in OTA nephrotoxicity and its supplementation may be effective strategies for the protection.

Emerging fatal gout disease in Chinese goslings linked to acute kidney injury induced by novel goose astrovirus infection.

A novel goose astrovirus (GAstV) has broken out across China in recent years, causing widespread damage to the poultry industry. In goslings infected with GAstV, the leading cause of death is visceral gout. However, our understanding of the mechanism of gout formation in GAstV infection is largely inadequate. The aim of this study was to examine the pathogenicity of a GAstV strain and explore the molecular mechanisms of visceral gout caused by viral infection in goslings. The virulent GAstV strain HR2105/1 was effectively isolated from the visceral tissue of goslings in gout-affected areas. The whole genome of the HR2105/1 strain was sequenced and analyzed. Subsequently, we established a gosling gout models with experimental GAstV infection. Finally, we conducted a study on the mechanism of GAstV induced acute kidney injury. Phylogenetic analysis of the complete genome sequence showed that it was closely related to the strain circulating in China since 2016, and it was grouped within the GAstV-1 cluster. The clinical signs were reproduced by experimental infection of healthy goslings with the isolated strain and were found to be similar to those reported in clinical cases. Moreover, the virus exhibits strong renal tropism. Infection with the GAstV strain HR2105/1 was found to cause acute kidney injury, as evidenced by increased levels of uric acid and creatinine as well as severe pathological damage. Mechanistic experiments with Masson and Picrosirius Red staining revealed fibrosis in renal tissues after GAstV infection. Furthermore, TUNEL staining revealed that GAstV infection triggered renal cell apoptosis. Additionally, RT-qPCR revealed that GAstV infection caused an excessive inflammatory response by upregulating the expression of IL-1β, IL-6, IL-10, TGF-β, and iNOS in renal tissues. Overall, our findings demonstrate that GAstV infection causes renal damage by inducing renal cell apoptosis, fibrosis, and excessive inflammatory response, which subsequently leads to hyperuricemia and lethal visceral gout formation. This is the first systematic study on the etiology of lethal gout in goslings caused by GAstV infection, and we believe that the findings can guide vaccine development and therapeutic targets for GAstV-associated renal diseases.

The telencephalon is a neuronal substrate for systemic inflammatory responses in teleosts via polyamine metabolism

Systemic inflammation elicits sickness behaviors and fever by engaging a complex neuronal circuitry that begins in the preoptic area of the hypothalamus. Ectotherms such as teleost fish display sickness behaviors in response to infection or inflammation, seeking warmer temperatures to enhance survival via behavioral fever responses. To date, the hypothalamus is the only brain region implicated in sickness behaviors and behavioral fever in teleosts. Yet, the complexity of neurobehavioral manifestations underlying sickness responses in teleosts suggests engagement of higher processing areas of the brain. Using in vivo models of systemic inflammation in rainbow trout, we find canonical pyrogenic cytokine responses in the hypothalamus whereas in the telencephalon and the optic tectum il-1b and tnfa expression is decoupled from il-6 expression. Polyamine metabolism changes, characterized by accumulation of putrescine and decreases in spermine and spermidine, are recorded in the telencephalon but not hypothalamus upon systemic injection of bacteria. While systemic inflammation causes canonical behavioral fever in trout, blockade of bacterial polyamine metabolism prior to injection abrogates behavioral fever, polyamine responses, and telencephalic but not hypothalamic cytokine responses. Combined, our work identifies the telencephalon as a neuronal substrate for brain responses to systemic inflammation in teleosts and uncovers the role of polyamines as critical chemical mediators in sickness behaviors.

PSI-8 Inflammatory cytokine concentrations and gene expression in mature and aging sedentary horses

Abstract Chronic inflammation associated with aging, termed “inflamm-aging” may negatively impact overall animal health. However, the mechanisms of inflamm-aging and, therefore, effective interventions, remain unknown. Nuclear factor erythroid 2-related factor 2 (Nrf2; NFE2L2) is a transcription factor that controls antioxidant gene expression and could be a target for promoting anti-inflammatory pathways. To test the hypothesis that supplementation of nonenzymatic derived antioxidants (Protandim Nrf2 Synergizer, LifeVantage Corporation) would activate Nrf2 and mitigate inflammation, 40 mature, sedentary horses [32 mares, 8 geldings; 15.7 ± 4.9 yr of age, body weight (BW) = 519 ± 46 kg] were stratified by age, sex, and BW and randomly assigned to one of four dietary treatment groups for 56 d: 1) 0 mg (CON); 2) 675 mg (Pro1); 3) 2,025 mg (Pro3); or 4) 4,050 mg (Pro6) Protandim Nrf2 Synergizer per day (n = 10 per group). Blood samples were collected at d 0 (September, 27°C, 61.6% humidity), d 28 (October, 21.6°C, 55.8% humidity), and d 56 (November, 15.1°C, 73.8% humidity) of supplementation prior to the morning feeding. Plasma cytokine concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-4, IL-6, IL-8, and IL-10 were quantified using custom Meso Scale Discovery U-Plex kits and whole blood gene expression of IL-1β, NFE2L2, and heme oxygenase 1 (HMOX1) were determined using qRT-PCR. Data were analyzed using PROC MIXED in SAS v9.4 with sex, time, treatment, age (under or over 15 yr), and time × treatment as fixed effects and time as a repeated effect with horse(treatment) as the subject. Day 0 was included as a covariate when treatment groups differed at d 0. Relationships between age and cytokine concentrations or mRNA expression were determined using PROC CORR. Plasma IL-4 (r = 0.4054) concentrations as well as whole blood HMOX1 (r = 0.3437) and NFE2L2 (r = 0.3382) expression on d 0 were positively correlated with age (P ≤ 0.04). Regardless of treatment or age, IL-1β and NFE2L2 expression and IL-4 and IL-8 concentrations decreased from d 0 to 28 (P ≤ 0.03) and remained depressed at d 56 (P ≤ 0.02) while IL-10 was not different from d 0 to 28 but decreased from d 0 to 56 (P = 0.02). TNFα concentrations were not different between treatments or over time. These data corroborate increased inflammatory markers with age and suggest a change in inflammatory status over time potentially due to seasonal environmental factors.

Effect of β-1,4-GalTI on the biological function of astrocytes treated by LPS.

Inflammation of the central nervous system (CNS) is a common feature of neurological disorders and infections, playing a crucial role in the development of CNS-related conditions. CNS inflammation is primarily regulated by glial cells, with astrocytes being the most abundant type in the mammalian CNS. Numerous studies have demonstrated that astrocytes, as immunocompetent cells, perform diverse and complex functions in both health and disease. Glycosylation, a critical post-translational modification of proteins, regulates numerous biological functions. The expression and activity of glycosyltransferases, the enzymes responsible for glycosylation, are closely associated with the pathogenesis of various diseases. β-1,4-GalTI, a mammalian glycosyltransferase, plays a significant role in cell-cell interactions, adhesion, and migration. Although many studies have focused on β-1,4-GalTI, few have explored its effects on astrocyte function. In this study, we constructed lentiviral vectors for both interference and overexpression of β-1,4-GalTI and discovered that β-1,4-GalTI knockdown inhibited astrocyte migration and proliferation, while its overexpression promoted these processes. Concurrently, β-1,4-GalTI knockdown reduced the expression of TNF-α, IL-1β, and IL-6, whereas overexpression enhanced the expression of these cytokines. These findings suggest that modulating β-1,4-GalTI activity can influence the molecular functions of astrocytes and provide a theoretical foundation for further research into β-1,4-GalTI as a potential therapeutic target in astrocyte-mediated inflammation.

Establishment of Nano-ITO induced rat model of indium lung disease and exploration of its pathological characteristics

Objective: To study the dynamic pathological characteristics of lung tissue in a Nano-ITO induced rat model of indium lung disease and to guide clinical and basic scientific research to further explore the mechanisms of pulmonary interstitial injury and pulmonary alveolar proteinosis (PAP). Methods: Dose-response (three divided doses) and time-course studies (six exposure periods) were performed to investigate the pulmonary toxicity induced by Nano-ITO. At the end of the experiment, cytokine levels and oxidative stress were analyzed in the bronchoalveolar lavage fluid. Rat lung tissues were also collected for staining with H&E, PAS, Masson's, Oil Red O, and Sirius Red. Ultrastructure of lung tissue cells was observed by transmission electron microscopy. Expression of IL-1β, HO-1, SP-A was observed by immunohistochemistry, and the expression of α-SMA was observed by immunofluorescence. Results: Nano-ITO intratracheal instillation caused pulmonary toxicity by inducing acute inflammation at 3 days, granuloma (nodule) formation and collagen hyperplasia at 14 days, and alveolar proteinosis at 56 days post-exposure. Pathological features of lung tissue included typical alveolar exudates, cellular fibrous nodules, enlarged alveolar fat droplet fusion, cholesterol crystal granuloma and pulmonary alveolar proteinosis. The intra-alveolar eosinophilic material (multilamellated, lattice-shaped, and myelin-like structure) showed abnormal lamellar bodies (features of alveolar type Ⅱ epithelial cells) and abundant rough endoplasmic reticulum and mitochondria (features of fibroblasts) on transmission electron microscopy of the lung tissue from rats exposed to Nano-ITO on the 84th day. Cellular pathology revealed that a large amount of amorphous PAS stain-positive substances appear in BALF at 28 days post-exposure, and pink granular protein-like substances can be seen in alveolar macrophages. Conclusions: There are three characteristic developmental stages in Nano-ITO induced pulmonary injury in rats, acute inflammation, granuloma (nodule) formation and collagen proliferation, and pulmonary alveolar proteinosis, which provide a reference feature model for the pathogenesis of indium lung disease.