505 Late-Breaking: Ruminal Microbiota, Inflammation Cytokines, and Performance of High-yield Dairy Cows Supplemented with Saccharomyces Cerevisiae Culture

Dramatic increases in milk yields in recent decades have created challenges in terms of rumen pH and microbial health which ultimately impact dairy cow health. The objective of this study was to assess the effects on ruminal pH, Volatile Fatty Acid (VFA), microbiota, inflammation, and performance of high-yield dairy cows by supplementing Saccharomyces cerevisiae culture (SC). Forty Holstein cows were divided into two groups based on their milk yield, days of milk, and parity fed the same basal ration diet that did or did not contain 100 g of SC /cow per day. Individual dry matter intake (DMI) and milk yield were recorded each day. Rumen fluid and milk samples were collected after 2 hours of morning feeding at intervals of 15 days during the experiment period. The data showed that rumen pH was increased by 0.19 (P = 0.09) when SC was supplemented than no SC was provided. SC-supplemented cow consumed 0.28 kg (P < 0.05) extra DM/d. Those supplemented with SC produced 1.36 kg (P < 0.05) more milk/cow per day than did non-supplemented cows. Milk fat percentage was higher (4.11 vs. 3.96%) for cows receiving SC. There were no differences in milk protein percentage. Rumen fluid VFA concentration was not statistically affected by SC but was numerically higher acetic and lower propionic for supplemented cows. The blood of the SC group with lower inflammation cytokines and somatic cell count (SCC). SC-supplemented cows had a greater relative abundance of Prevotellaceae, Succinivibrionaceae, Fibrobacteraceae, Lactobacillaceae, and lower relative abundance of Spirochaetaceae, Methanobacteriaceae, Enterobacteriaceae than the unsupplemented cows. It had greater functions on xylanolysis, fermentation, cellulolysis in the rumen in terms of the KEGG function prediction analysis. This study demonstrated that high-yield lactation cows receiving supplemental SC produced more milk and potentially reduced the inflammation and enhanced rumen cellulolysis bacteria growth.

Cytokines and progressive chronic kidney disease in children

The problem of chronickidney disease is one of the urgent problems in nephrology. There is data on the multifaceted participation of cytokines in the development and prognosis of pathological conditions. The recent studies are focusedon the mechanismsoflocal inflammation with the analysis of interleukins level in the urine. Cytokines are mediators between nonspecific defense reactions and specificimmunity. Being synthesized in the focus of inflammation, cytokines influence almost all cells involvedin inflammation. In case of local defense failure, cytokines enterthe circulation and act at the systemic level, developing an acutephaseresponse in the body. The review presents data on the cytokine status in chronic kidney disease in children and its rolein the progression oft he disease. The authors emphasize the scientific and practical significance of studies of the cytokine status in chronic kidney diseases.

Brain Transcriptome of Autism Spectrum Disorders and Tourette Syndrome Defines Common Targetable Inflammatory Pathways Involving Cytokines, Complement, and Kinase Signalling

BackgroundNeurodevelopmental disorders (NDDs), including autism-spectrum disorders (ASD) and Tourette syndrome (TS) are common brain conditions which often co-exist, however current management focuses on symptom mitigation, with no approved treatments targeting disease mechanisms. There is accumulating literature implicating the immune system in NDDs, and transcriptomics of post-mortem brain tissue from individuals with NDDs has revealed an inflammatory signal. MethodsWe interrogated two RNA-sequencing datasets of ASD and TS (compared to age-matched controls) and identified the top 1000 differentially expressed genes, to explore commonly enriched pathways using an over-representation analysis through GO, KEGG and Reactome.ResultsIn the ASD analysis, the top 1000 DEGs enriched 754 GO terms (all upregulated), 55 KEGG pathways (54 upregulated), and 109 Reactome pathways (all upregulated), involving inflammation, cytokines, complement, cell signalling and epigenetic regulation. In the TS analysis, the top 1000 DEGs enriched 419 GO terms (416 upregulated), 56 KEGG pathways (all upregulated), and 28 Reactome (all upregulated) pathways, including inflammation, cytokines, signal transduction and immune response to stimuli. Of the top 1000 DEGs from the ASD and TS analyses, 133 DEGs were shared. Interaction networks of the common protein-coding DEGs using STRING revealed 5 central up-regulated hub genes: CSF2RB, HCK, HCLS1, LCP2 and PLEK, which are all kinases involved in cell signalling. Applying KEGG and Reactome analysis to these common DEGs identified pathways involving interleukins, complement activation, and cell signalling pathways. ConclusionsThese findings bring new evidence of shared inflammation in ASD and TS, and provide therapeutic opportunities targeting inflammation, epigenetic machinery, and cell signalling including kinases.

Ageratina adenophora Disrupts the Intestinal Structure and Immune Barrier Integrity in Rats

The aim of this study was to investigate the effects of Ageratina adenophora on the intestines morphology and integrity in rat. Rats were randomly divided into two groups and were fed with 10 g/100 g body weight (BW) basal diet and 10 g/100 g BW experimental diet, which was a mixture of A. adenophora powder and basal diet in a 3:7 ratio. The feeding experiment lasted for 60 days. At days 28 and 60 of the experiment, eight rats/group/timepoint were randomly selected, weighed, and sacrificed, then blood and intestinal tissues were collected and stored for further analysis. The results showed that Ageratina adenophora caused pathological changes and injury in the intestine, elevated serum diamine oxidase (DAO), D-lactate (D-LA), and secretory immunoglobulin A (sIgA) levels, reduced occludin levels in intestinal tissues, as well as increased the count of intraepithelial leukocytes (IELs) and lamina propria leukocytes (LPLs) in the intestine (p < 0.05 or p < 0.01). In addition, the mRNA and protein (ELISA) expressions of pro-inflammation cytokines (IL-1β, IL-2, TNF-α, and IFN-ϒ) were elevated in the Ageratina adenophora treatment groups, whereas anti-inflammatory cytokines such as IL-4 and IL-10 were reduced (p < 0.01 or p < 0.05). Therefore, the results obtained in this study indicated that Ageratina adenophora impaired intestinal function in rats by damaging the intestine structure and integrity, and also triggered an inflammation immune response that led to intestinal immune barrier dysfunction.

Yifei Sanjie Formula Treats Chronic Obstructive Pulmonary Disease by Regulating Lung Microbiota Dysbiosis

BackgroundChronic obstructive pulmonary disease (COPD) is one of the most common pulmonary diseases. There is evidence to suggest that dysbiosis of pulmonary microbiota participates in COPD development. Yifei Sanjie Formula (YS) is widely used to treat diseases in respiratory systems, yet its mechanisms are little known. MethodsIn the present study, the efficacy of YS was evaluated by analyzing its effects on the severity of pulmonary pathological damage, pulmonary function, pro-inflammation cytokines, the activation of NLRP3/caspase-1/IL-1β signaling pathway, and changes of lung microbiota. ResultsYS improved animal behaviors, prevented declines in pulmonary ventilatory function and lung injury in a rat model of COPD. Administration of YS significantly suppressed the release of proinflammatory cytokines and collagen deposition and downregulated NLRP3/caspase-1/IL-1β signaling in vivo. YS changed the relative abundance of specific pulmonary microbiota and modulated bacterial flora in the rat model. ConclusionsThese results suggest that the effects of YS involved lung microbes and anti-inflammatory mechanisms.

Th17 Cells in Periodontitis and Its Regulation by A20

Periodontitis is a prevalent chronic disease that results in loss of periodontal ligament and bone resorption. Triggered by pathogens and prolonged inflammation, periodontitis is modulated by the immune system, especially pro-inflammatory cells, such as T helper (Th) 17 cells. Originated from CD4+ Th cells, Th17 cells play a central role for they drive and regulate periodontal inflammation. Cytokines secreted by Th17 cells are also major players in the pathogenesis of periodontitis. Given the importance of Th17 cells, modulators of Th17 cells are of great clinical potential and worth of discussion. This review aims to provide an overview of the current understanding of the effect of Th17 cells on periodontitis, as well as a brief discussion of current and potential therapies targeting Th17 cells. Lastly, we highlight this article by summarizing the causal relationship between A20 (encoded by TNFAIP3), an anti-inflammatory molecule, and Th17 cell differentiation.

Overexpression of mm9_circ_013935 alleviates renal inflammation and fibrosis in diabetic nephropathy via the miR-153-3p/NFIC axis

Background: Circ-RBM4 (mm9_circ_013935) has been revealed to be low-expressed in the renal tissues of diabetic nephropathy (DN) mice while its underlying regulatory mechanism remains unexplored. Methods: The high glucose (HG)-treated mouse podocytes were used to establish the DN cell models. A CCK-8 assay was used to examine the viability of mouse podocytes. The expression of proteins related to fibrosis (Collagen I, Collagen III, fibronectin) was detected using western blot. The concentration of inflammation cytokines (TNF-α, IL-1β, IL-8) in mouse podocytes was assessed by ELISA. The interaction between genes was explored by luciferase reporter assays. Results: HG treatement decreased the viability and elevated the expression of fibrosis and inflammation factors in mouse podocytes. Circ-RBM4 expression was downregulated in HG-treated mouse podocytes. Circ-RBM4 overexpression reversed HG-induced increase in levels of proteins related to fibrosis and the concentration of inflammation factors. MiR-153-3p was revealed to bind with circ-RBM4 and directly targeted nuclear factor I/C (NFIC) in mouse podocytes. Rescue assays indicated that circ-RBM4 attenuated HG-induced fibrosis and inflammation response in mouse podocytes by inhibiting miR-153-3p expression or upregulating NFIC expression. Conclusion: Circ-RBM4 alleviated the renal inflamation and renal fibrosis in DN by targeting the miR-153-3p/NFIC axis.

Self-developed NF-κB inhibitor 270 protects against LPS-induced acute kidney injury and lung injury through improving inflammation

Background and Purpose: Sepsis-induced acute kidney injury (AKI) and acute lung injury (ALI) have high morbidity and mortality, with no effective clinically available drugs. Anti-inflammation is effective strategy in the therapy of AKI and ALI. NF-κB is a target for the development of anti‑inflammatory agents. The purpose of the study is to evaluate the effect of 270, self-developed NF-κB inhibitor, in LPS-induced AKI and ALI. Experimental Approach: LPS-induced macrophages were used to examine the anti-inflammation activity of 270. Sepsis-induced AKI and ALI mice models were established by intraperitoneal injection of LPS (10 mg/kg) for 24 h. Oral administration 270 for 14 days before LPS stimulation. Plasma, kidney and lung tissues were collected and used for histopathology, biochemical assay, ELISA, RT-PCR, and western blot analyses. Key Results: In vitro, we showed that 270 suppressed the inflammation response in LPS-induced RAW 264.7 macrophages and bone marrow derived macrophages. In vivo, we found that 270 ameliorated LPS-induced AKI and ALI, as evidenced by improving various pathological changes, reducing the expression of pro-inflammation genes, blocking the activation of NF-κB and JNK pathways, attenuating the elevated myeloperoxidase (MPO) activity and malondialdehyde (MDA) content, ameliorating the activated ER stress, reversing the inhibition effect on autophagy in kidney and lung tissues, and alleviating the enhanced plasma level of creatinine (Crea), blood urea nitrogen (BUN) and pro-inflammation cytokines. Conclusions and Implications: Our investigations provides evidence that NF-κB inhibitor 270 is a potential drug against LPS-induced AKI and ALI in the future.

Bacillus Licheniformis PF9 Improves Barrier Function and Alleviates Inflammatory Responses Against Enterotoxigenic Escherichia Coli F4 Infection in the Porcine Intestinal Epithelial Cells

Background: Enterotoxigenic Escherichia coli (ETEC) F4 commonly colonizes the small intestine and releases enterotoxins that impair the intestinal barrier function and trigger inflammatory responses. Although Bacillus licheniformis (B. licheniformis) has been reported to enhance intestinal health, it remains to be seen whether there is a functional role of B. licheniformis in intestinal inflammatory response in intestinal porcine epithelial cell line (IPEC-J2) when stimulated with ETEC F4.Methods: In the present study, the effects of B. licheniformis PF9 on the release of pro-inflammation cytokines, cell integrity and nuclear factor-κB (NF-κB) activation were evaluated in ETEC F4-induced IPEC-J2 cells.Results: B. licheniformis PF9 treatment was capable of remarkably attenuating the expression levels of inflammation cytokines tumor necrosis factor-α (TNF-α), interleukin (IL)-8, and IL-6 during ETEC F4 infection. Furthermore, the gene expression of Toll-like receptor 4 (TLR4)-mediated upstream related genes of NF-κB signaling pathway has been significantly inhibited. These changes were accompanied by a significant decreased phosphorylation of p65 NF-κB during ETEC F4 infection with B. licheniformis PF9 treatment. The immunofluorescence and western blot analysis revealed that B. licheniformis PF9 increased the expression levels of zona occludens 1 (ZO-1) and occludin (OCLN) in ETEC F4-infected IPEC-J2 cells. Meanwhile, the B. licheniformis PF9 could alleviate the epithelial barrier function assessed by the trans-epithelial electrical resistance (TEER) and cell permeability assay. Interestingly, B. licheniformis PF9 protect IPEC-J2 cells against ETEC F4 infection by decreasing the gene expressions of virulence-related factors (including luxS, estA, estB, and elt) in ETEC F4.Conclusions: Collectively, our results suggest that B. licheniformis PF9 might reduce inflammation-related cytokines through blocking the NF-κB signaling pathways. Besides, B. licheniformis PF9 displayed a significant role in the enhancement of IPEC-J2 cell integrity.