Baicalin Protects Vascular Tight Junctions in Piglets During Glaesserella parasuis Infection.

Glaesserella parasuis (G. parasuis) can cause Glässer's disease and severely affect swine industry worldwide. This study is an attempt to address the issue of the capability of G. parasuis to damage the vascular barrier and the effects of baicalin on vascular tight junctions (TJ) in order to investigate the interactions between the pathogen and the porcine vascular endothelium. Piglets were challenged with G. parasuis and treated with or without baicalin. The expressions of vascular TJ genes were examined using RT-PCR. The distribution patterns of TJ proteins were detected by immunofluorescence. The involved signaling pathways were determined by Western blot assays on related proteins. G. parasuis can downregulate TJ expression and disrupt the distribution of TJ proteins. Baicalin can alleviate the downregulation of vascular TJ mRNA, maintain the distribution, and prevent the abnormalities of TJ. These results provide ample evidence that baicalin has the capacity to protect vascular TJ damaged by G. parasuis through inhibiting PKC and MLCK/MLC pathway activation. As a result, baicalin is a promising candidate for application as a natural agent for the prevention and control of G. parasuis infection.

Metagenomic Sequencing Analysis of the Effects of Colistin Sulfate on the Pig Gut Microbiome.

The gut microbiome plays important roles in maintaining host health, and inappropriate use of antibiotics can cause imbalance, which may contribute to serious disease. However, despite its promise, using metagenomic sequencing to explore the effects of colistin on gut microbiome composition in pig has not been reported. Herein, we evaluated the roles of colistin in gut microbiome modulation in pigs. Metagenomic analysis demonstrated that overall microbial diversity was higher in the colistin group compared with the control group. Antibiotic Resistance Genes Database analysis demonstrated that following colistin treatment, expression levels of tsnr, ant6ia, tetq, oleb, norm, ant3ia, and mexh were significantly upregulated, indicating that colistin may induce transformation of antibiotic resistance genes. Colistin also affected the microbiome distribution patterns at both genus and phylum levels. In addition, at the species level, colistin significantly reduced the abundance of Prevotella copri, Phascolarctobacterium succinatutens, and Prevotella stercorea and enhanced the abundance of Treponema succinifaciens and Acidaminococcus fermentans compared to the control group. Gene Ontology analysis demonstrated that following treatment with colistin, metabolic process, cellular process, and single-organism process were the dominant affected terms. Kyoto Encyclopedia of Genes and Genomes analysis showed that oxidative phosphorylation, protein processing in endoplasmic reticulum, various types of N-glycan biosynthesis, protein processing in endoplasmic reticulum, pathogenic Escherichia coli infection, and mitogen-activated protein kinase signaling pathway-yeast were the dominant signaling pathways in the colistin group. Overall, our results suggested that colistin affects microbial diversity and may modulate gut microbiome composition in pig, potentially providing novel strategy or antibiotic rationalization pertinent to human and animal health.

Baicalin-Aluminum Modulates the Broiler Gut Microbiome.

Baicalin-aluminum regulates the gut microbiome of piglets with diarrhea. However, whether it affects poultry gut microbiome composition and function remains unknown. In this study, we used metagenomic sequencing to explore the effects of baicalin-aluminum on gut microbiome changes in poultry when compared with animals administered colistin sulfate. Our data showed that important gut microbiome components consisted of Ruminococcaceae, Subdoligranulum, Bifidobacterium, Bifidobacterium pseudolongum, and Pseudoflavonifractor when broilers were administered baicalin-aluminum compared with colistin. At the species level, Lactobacillus salivarius, Bacteroides uniformis, Oscillibacter unclassified, Bacteroides fragilis, Ruminococcus torques, and Subdoligranulum unclassified abundance were significantly upregulated upon baicalin-aluminum treatment when compared with colistin administration. In addition, Gene Ontology (GO) enrichment analysis indicated that functional differentially expressed genes, which were in the top 30 GO enrichment terms, were associated with metabolic processes, catalytic activity, and cellular processes. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated that ABC transporters, oxidative phosphorylation, and phosphotransferase systems were the dominant signaling pathways in the baicalin-aluminum group when compared with the colistin group. Taken together, our data indicated that baicalin-aluminum modified broiler gut microbiome composition. These observations enhance our physiological insights of baicalin-aluminum-mediated functions in the broiler microbiome and potentially provide a novel therapy to manage both animal and human health.

Effect of Baicalin on Transcriptome Changes in Piglet Vascular Endothelial Cells Induced by a Combination of Glaesserella parasuis and Lipopolysaccharide.

Glaesserella parasuis causes porcine Glässer's disease and lipopolysaccharide (LPS) induces acute inflammation and pathological damage. Baicalin has antioxidant, antimicrobial, and anti-inflammatory functions. Long noncoding RNAs (lncRNAs) play key regulatory functions during bacterial infection. However, the role of lncRNAs in the vascular dysfunction induced by a combination of G. parasuis and LPS during systemic inflammation and the effect of baicalin on lncRNA expression induced in porcine aortic vascular endothelial cells (PAVECs) by a combination of G. parasuis and LPS have not been investigated. In this study, we investigated the changes in lncRNA and mRNA expression induced in PAVECs by G. parasuis, LPS, or a combination of G. parasuis and LPS, and the action of baicalin on lncRNA expression induced in PAVECs by the combination of G. parasuis and LPS. Our results showed 133 lncRNAs and 602 genes were differentially expressed when PAVECs were stimulated with the combination of G. parasuis and LPS, whereas 107 lncRNAs and 936 genes were differentially expressed when PAVECs were stimulated with the combination of G. parasuis and LPS after pretreatment with baicalin. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed the dominant signaling pathways triggered by the combination of G. parasuis and LPS were the tumor necrosis factor signaling pathway, phosphatidylinositol signaling system, and inositol phosphate metabolism. Protein-protein interaction network analysis showed the differentially expressed target genes of the differentially expressed lncRNAs (DELs) were related to each other. A coexpression analysis indicated the expression levels of the DELs were co-regulated with those of their differentially expressed target genes. This is the first study to systematically compare the changes in lncRNAs and mRNAs in PAVECs stimulated with a combination of G. parasuis and LPS. Our data clarified the mechanisms underlying the vascular inflammation and damage triggered by G. parasuis and LPS, and it may provide novel targets for the treatment of LPS-induced systemic inflammation.

Necroptosis Underlies Hepatic Damage in a Piglet Model of Lipopolysaccharide-Induced Sepsis.

Background: Necroptosis is a newly recognized form of programmed cell death with characteristics of both necrosis and apoptosis. The role of necroptosis in hepatic damage during sepsis is poorly understood. In this study, we investigated the occurrence of necroptosis in hepatic damage, and its contribution to hepatic damage in a piglet model of lipopolysaccharide (LPS)-induced sepsis. Methods: Two animal experiments were conducted. In trial 1, piglets were challenged with LPS and sacrificed at different time points after LPS challenge. In trial 2, piglets were pretreated with necrostatin-1, a specific inhibitor of necroptosis, prior to LPS challenge. Alterations in the hepatic structure and function, pro-inflammatory cytokine expression, and the necroptosis signaling pathway were investigated. Typical ultrastructural characteristics of cell necrosis was observed in the liver of LPS-challenged piglets. Results: Expressions of critical components of necroptosis including kinases (RIP1, RIP3, and MLKL), mitochondrial proteins (PGAM5 and DRP1), and an intracellular damage-associated molecular pattern (HMGB1) were increased in the liver in a time-dependent manner, followed by hepatic inflammation, morphological damage, and dysfunction as manifested by elevated hepatic expression of IL-1ß, IL-6 and TNF-α as well as increased serum AST and AKP activities and the AST/ALT ratio. Pretreatment with necrostatin-1 significantly reduced the expression of RIP1, RIP3 and MLKL as well as PGAM5, DRP1 and HMGB1, which subsequently led to obvious attenuation of hepatic inflammation and damage. Conclusions: Our study demonstrates that necroptosis occurs in the liver during sepsis and contributes to septic hepatic injury.

Protective Effects of Baicalin on Peritoneal Tight Junctions in Piglets Challenged with Glaesserella parasuis.

Glaesserella parasuis (G. parasuis) causes inflammation and damage to piglets. Whether polyserositis caused by G. parasuis is due to tight junctions damage and the protective effect of baicalin on it have not been examined. Therefore, this study aims to investigate the effects of baicalin on peritoneal tight junctions of piglets challenged with G. parasuis and its underlying molecular mechanisms. Piglets were challenged with G. parasuis and treated with or without baicalin. RT-PCR was performed to examine the expression of peritoneal tight junctions genes. Immunofluorescence was carried out to detect the distribution patterns of tight junctions proteins. Western blot assays were carried out to determine the involved signaling pathways. Our data showed that G. parasuis infection can down-regulate the tight junctions expression and disrupt the distribution of tight junctions proteins. Baicalin can alleviate the down-regulation of tight junctions mRNA in peritoneum, prevent the abnormalities and maintain the continuous organization of tight junctions. Our results provide novel evidence to support that baicalin has the capacity to protect peritoneal tight junctions from G. parasuis-induced inflammation. The protective mechanisms of baicalin could be associated with inhibition of the activation of PKC and MLCK/MLC signaling pathway. Taken together, these data demonstrated that baicalin is a promising natural agent for the prevention and treatment of G. parasuis infection.

The effects of baicalin on piglets challenged with Glaesserella parasuis.

Glaesserella parasuis (G. parasuis) causes porcine vascular inflammation and damage. Baicalin is reported to have antioxidant and anti-inflammatory functions. However, whether baicalin protects piglets against G. parasuis challenge and the potential protective mechanism have not been investigated. Therefore, in this study, we comprehensively examined the protective efficacy of baicalin in piglets challenged with G. parasuis and the possible protective mechanism. Our results show that baicalin attenuated the release of the inflammation-related cytokines interleukin (IL) 1ß, IL6, IL8, IL10, and tumour necrosis factor α (TNF-α) and reduced high mobility group box 1 (HMGB1) production and cell apoptosis in piglets infected with G. parasuis. Baicalin also inhibited the activation of the mitogen-activated protein kinase (MAPK) signalling pathway and protected piglets against G. parasuis challenge. Taken together, our data suggest that baicalin could protect piglets from G. parasuis by reducing HMGB1 release, attenuating cell apoptosis, and inhibiting MAPK signalling activation, thereby alleviating the inflammatory response induced by the bacteria. Our results suggest that baicalin has utility as a novel therapeutic drug to control G. parasuis infection.

The effect of baicalin on microRNA expression profiles in porcine aortic vascular endothelial cells infected by Haemophilus parasuis.

Glässer's disease, caused by Haemophilus parasuis (H. parasuis), is associated with vascular damage and vascular inflammation in pigs. Therefore, early assessment and treatment are essential to control the inflammatory disorder. MicroRNAs have been shown to be involved in the vascular pathology. Baicalin has important pharmacological functions, including anti-inflammatory, antimicrobial and antioxidant effects. In this study, we investigated the changes of microRNAs in porcine aortic vascular endothelial cells (PAVECs) induced by H. parasuis and the effect of baicalin in this model by utilizing high-throughput sequencing. The results showed that 155 novel microRNAs and 76 differentially expressed microRNAs were identified in all samples. Subsequently, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the target genes of the differentially expressed microRNAs demonstrated that regulation of actin cytoskeleton, focal adhesion, ECM-receptor interaction, bacterial invasion of epithelial cells, and adherens junction were the most interesting pathways after PAVECs were infected with H. parasuis. In addition, when the PAVECs were pretreated with baicalin, mismatch repair, peroxisome, oxidative phosphorylation, DNA replication, and ABC transporters were the most predominant signaling pathways. STRING analysis showed that most of the target genes of the differentially expressed microRNAs were associated with each other. The expression levels of the differentially expressed microRNAs were negatively co-regulated with their target genes' mRNA following pretreatment with baicalin in the H. parasuis-induced PAVECs using co-expression networks analysis. This is the first report that microRNAs might have key roles in inflammatory damage of vascular tissue during H. parasuis infection. Baicalin regulated the microRNAs changes in the PAVECs following H. parasuis infection, which may represent useful novel targets to prevent or treat H. parasuis infection.

Activation of the NF-κB and MAPK Signaling Pathways Contributes to the Inflammatory Responses, but Not Cell Injury, in IPEC-1 Cells Challenged with Hydrogen Peroxide.

Oxidative stress can lead to intestinal cell injury as well as the induction of inflammation. It is not clear whether inflammation is an important factor leading to cell injury caused by oxidative stress. The purpose of this study was to investigate the role of inflammation in intestinal injury caused by hydrogen peroxide (H2O2). Our results revealed that H2O2 stimulation significantly decreased the viability of intestinal porcine epithelial cells (IPEC-1), increased lactate dehydrogenase (LDH) activity, and disrupted the distribution of the tight junction protein claudin-1. H2O2 significantly increased the mRNA expression of interleukin-6 (IL-6), IL-8, and tumor necrosis factor-α (TNF-α). H2O2 stimulation also led to increased phosphorylation of p38 and jun N-terminal kinase (JNK), and p65 NF-κB protein translocation into the nucleus of IPEC-1 cells. Cells treated with the NF-κB inhibitor (BAY11-7082), the p38 inhibitor (SB202190), or the JNK inhibitor (PD98059) significantly decreased mRNA and protein expression of IL-6, IL-8, and TNF-α. However, treatment with mitogen-activated protein kinase (MAPK) or NF-κB inhibitors did not prevent the damage effect on cell viability, LDH activity, or the distribution of claudin-1 in cells challenged with H2O2. In summary, our data demonstrate that activation of the NF-κB and MAPK signaling pathways can contribute to the inflammatory response, but not cell injury, in IPEC-1 cells challenged with H2O2.

The Effect of Baicalin on the Expression Profiles of Long Non-Coding RNAs and mRNAs in Porcine Aortic Vascular Endothelial Cells Infected with Haemophilus parasuis.

Haemophilus parasuis can elicit serious inflammatory responses, which contribute to huge economic losses to the swine industry. However, the pathogenic mechanisms underlying inflammation-related damage induced by H. parasuis remain unclear. Accumulating evidence indicates that long non-coding RNAs (lncRNAs) have important functions in the regulation of autoimmune disorders. Baicalin has been shown to have anti-inflammatory, anti-microbial, and anti-oxidant activities. In this study, we investigated whether lncRNAs were involved in the vascular injury or inflammation triggered by H. parasuis and whether baicalin regulated the lncRNA profiles of porcine aortic vascular endothelial cells (PAVECs) infected with H. parasuis. The results showed that the lncRNA and mRNA expression profiles of PAVECs were changed by H. parasuis. Important functions of lncRNAs and mRNAs were predicted. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses demonstrated that the targets of differentially expressed lncRNAs of H. parasuis infected PAVECs were mainly involved in the tumor necrosis factor (TNF) signaling pathway, apoptosis, and N-glycan biosynthesis; whereas nicotinate and nicotinamide metabolism, the cytosolic DNA-sensing pathway, the TNF signaling pathway, and the nuclear factor (NF)-kappa B signaling pathway were enriched in PAVECs pretreated with baicalin. In addition, top hub genes and lncRNAs were identified and validated by quantitative polymerase chain reaction. CCL5, GBP1, and SAMHD1 were significantly upregulated after H. parasuis infection, whereas they were significantly downregulated with baicalin pretreatment. LncRNA ALDBSSCT0000001677, ALDBSSCT0000001353, MSTRG.10724.2, and ALDBSSCT0000010434 had the same expression pattern. Collectively, these data suggested that baicalin could modify changes to the lncRNAs profiles or regulate lncRNAs that participate in inflammation-related signaling pathways, thereby alleviating tissue damage or inflammatory responses induced by H. parasuis. To our best knowledge, this is the first article of H. parasuis stimulating changes to the lncRNA profiles of PAVECs and the capability of baicalin to regulate lncRNA changes in PAVECs infected with H. parasuis, which might provide a novel therapeutic target for the control of H. parasuis infection.

EPA and DHA attenuate deoxynivalenol-induced intestinal porcine epithelial cell injury and protect barrier function integrity by inhibiting necroptosis signaling pathway.

Deoxynivalenol (DON) is one of the most common mycotoxins that contaminates food or feed and cause intestinal damage. Long-chain n-3 polyunsaturated fatty acids (PUFA) such as EPA and DHA exert beneficial effects on intestinal integrity in animal models and clinical trials. Necroptosis signaling pathway plays a critical role in intestinal cell injury. This study tested the hypothesis that EPA and DHA could alleviate DON-induced injury to intestinal porcine epithelial cells through modulation of the necroptosis signaling pathway. Intestinal porcine epithelial cell 1 (IPEC-1) cells were cultured with or without EPA or DHA (6.25-25 µg/mL) in the presence or absence of 0.5 µg/mL DON for indicated time points. Cell viability, cell number, lactate dehydrogenase (LDH) activity, cell necrosis, transepithelial electrical resistance (TEER), fluorescein isothiocyanate-labeled dextran 4kDa (FD4) flux, tight junction protein distribution, and protein abundance of necroptosis related signals were determined. EPA and DHA promoted cell growth indicated by higher cell viability and cell number, and inhibited cell injury indicated by lower LDH activity in the media. EPA and DHA also improved intestinal barrier function, indicated by higher TEER and lower permeability of FD4 flux as well as increased proportions of tight junction proteins located in the plasma membrane. Moreover, EPA and DHA decreased cell necrosis demonstrated by live cell imaging and transmission electron microscopy. Finally, EPA and DHA downregulated protein expressions of necroptosis related signals including tumor necrosis factor receptor (TNFR1), receptor interacting protein kinase 1 (RIP1), RIP3, phosphorylated mixed lineage kinase-like protein (MLKL), phosphoglycerate mutase family 5 (PGAM5), dynamin-related protein 1 (Drp1), and high mobility group box-1 protein (HMGB1). EPA and DHA also inhibited protein expression of caspase-3 and caspase-8. These results suggest that EPA and DHA prevent DON-induced intestinal cell injury and enhance barrier function, which is associated with inhibition of the necroptosis signaling pathway.

Effect of Baicalin-Aluminum Complexes on Fecal Microbiome in Piglets.

The gut microbiome has important effects on gastrointestinal diseases. Diarrhea attenuation functions of baicalin (BA) is not clear. Baicalin-aluminum complexes (BBA) were synthesized from BA, but the BBA's efficacy on the diarrhea of piglets and the gut microbiomes have not been explored and the mechanism remains unclear. This study has explored whether BBA could modulate the composition of the gut microbiomes of piglets during diarrhea. The results showed that the diarrhea rate reduced significantly after treatment with BBA. BBA altered the overall structure of the gut microbiomes. In addition, the Gene Ontology (GO) enrichment analysis indicated that the functional differentially expressed genes, which were involved in the top 30 GO enrichments, were associated with hydrogenase (acceptor) activity, nicotinamide-nucleotide adenylyltransferase activity, and isocitrate lyase activity, belong to the molecular function. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that flagellar assembly, bacterial chemotaxis, lipopolysaccharide biosynthesis, ATP-binding cassette transporters (ABC) transporters, biosynthesis of amino acids, and phosphotransferase system (PTS) were the most enriched during BBA treatment process. Taken together, our results first demonstrated that BBA treatment could modulate the gut microbiomes composition of piglets with diarrhea, which may provide new potential insights on the mechanisms of gut microbiomes associated underlying the antimicrobial efficacy of BBA.

Effects of Baicalin on piglet monocytes involving PKC-MAPK signaling pathways induced by Haemophilus parasuis.

BACKGROUND: Haemophilus parasuis (HPS) is the causative agent of Glässer's disease, characterized by arthritis, fibrinous polyserositis and meningitis, and resulting in worldwide economic losses in the swine industry. Baicalin (BA), a commonly used traditional Chinese medication, has been shown to possess a series of activities, such as anti-bacterial, anti-viral, anti-tumor, anti-oxidant and anti-inflammatory activities. However, whether BA has anti-apoptotic effects following HPS infection is unclear. Here, we investigated the anti-apoptotic effects and mechanisms of BA in HPS-induced apoptosis via the protein kinase C (PKC)-mitogen-activated protein kinase (MAPK) pathway in piglet's mononuclear phagocytes (PMNP). RESULTS: Our data demonstrated that HPS could induce reactive oxygen species (ROS) production, arrest the cell cycle and promote apoptosis via the PKC-MAPK signaling pathway in PMNP. Moreover, when BA was administered, we observed a reduction in ROS production, suppression of cleavage of caspase-3 in inducing apoptosis, and inhibition of activation of the PKC-MAPK signaling pathway for down-regulating p-JNK, p-p38, p-ERK, p-PKC-α and PKC-δ in PMNP triggered by HPS. CONCLUSIONS: Our data strongly suggest that BA can reverse the apoptosis initiated by HPS through regulating the PKC-MAPK signaling pathway, which represents a promising therapeutic agent in the treatment of HPS infection.

Lentinan modulates intestinal microbiota and enhances barrier integrity in a piglet model challenged with lipopolysaccharide.

The intestinal microbiota plays a vital role in metabolism, pathogen resistance, and immune development in host cells, and is modifiable by dietary change. Lentinan (LNT), a type of mushroom polysaccharide, is known to ameliorate intestinal inflammation with the potential of therapeutic effect on digestive diseases. We hypothesized that LNT could alleviate Escherichia coli lipopolysaccharide (LPS)-induced intestinal injury via regulating the composition and metabolites of intestinal microbiota in a piglet model. Twenty-four weaned piglets were used in a 2 × 2 factorial design, and the main factors included a dietary treatment (basal or LNT diet) and immunological challenge (LPS or saline). After feeding basal or LNT diet for 21 days, pigs were injected with LPS or saline. At 4 h post-injection, pigs were killed and jejunum, ileum and cecal digesta were collected. LNT improved intestinal morphology and barrier function. LNT also inhibited inflammatory signaling pathways (toll-like receptor 4 and nucleotide binding oligomerization domain protein) and pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-1ß and interleukin-6) expression, as well as up-regulated the heat shock protein 70 expression in small intestine. In addition, LNT enhanced the concentrations of propionate, butyrate, isobutyrate and isovalerate in cecal digesta, resulting in a significant increase in histone acetylation without affecting the protein level of G protein-coupled receptor 41 (GPR41), a short chain fatty acid receptor. Bacterial 16S rRNA gene pyrosequencing showed that LNT had a great impact on gut microbiota composition at different taxonomic levels. Moreover, the correlation analysis revealed some potential relationships between cecal metabolites and certain intestinal microbiota. These results indicate that LNT promotes intestinal health, in part, through altering intestinal microbiota composition and increasing the short chain fatty acid synthesis, which subsequently lead to a reduction in inflammation and hyper-acetylation of histones.

Transcriptional Profiling of Host Cell Responses to Virulent Haemophilus parasuis: New Insights into Pathogenesis.

Haemophilus parasuis is the causative agent of Glässer’s disease in pigs. H. parasuis can cause vascular damage, although the mechanism remains unclear. In this study, we investigated the host cell responses involved in the molecular pathway interactions in porcine aortic vascular endothelial cells (PAVECs) induced by H. parasuis using RNA-Seq. The transcriptome results showed that when PAVECs were infected with H. parasuis for 24 h, 281 differentially expressed genes (DEGs) were identified; of which, 236 were upregulated and 45 downregulated. The 281 DEGs were involved in 136 KEGG signaling pathways that were organismal systems, environmental information processing, metabolism, cellular processes, and genetic information processing. The main pathways were the Rap1, FoxO, and PI3K/Akt signaling pathways, and the overexpressed genes were determined and verified by quantitative reverse transcription polymerase chain reaction. In addition, 252 genes were clustered into biological processes, molecular processes, and cellular components. Our study provides new insights for understanding the interaction between bacterial and host cells, and analyzed, in detail, the possible mechanisms that lead to vascular damage induced by H. parasuis. This may lead to development of novel therapeutic targets to control H. parasuis infection.

Baicalin Inhibits Haemophilus Parasuis-Induced High-Mobility Group Box 1 Release during Inflammation.

Haemophilus parasuis (H. parasuis) can cause Glässer’s disease in pigs. However, the molecular mechanism of the inflammation response induced by H. parasuis remains unclear. The high-mobility group box 1 (HMGB1) protein is related to the pathogenesis of various infectious pathogens, but little is known about whether H. parasuis can induce the release of HMGB1 in piglet peripheral blood monocytes. Baicalin displays important anti-inflammatory and anti-microbial activities. In the present study, we investigated whether H. parasuis can trigger the secretion of HMGB1 in piglet peripheral blood monocytes and the anti-inflammatory effect of baicalin on the production of HMGB1 in peripheral blood monocytes induced by H. parasuis during the inflammation response. In addition, host cell responses stimulated by H. parasuis were determined with RNA-Seq. The RNA-Seq results showed that H. parasuis infection provokes the expression of cytokines and the activation of numerous pathways. In addition, baicalin significantly reduced the release of HMGB1 in peripheral blood monocytes induced by H. parasuis. Taken together, our study showed that H. parasuis can induce the release of HMGB1 and baicalin can inhibit HMGB1 secretion in an H. parasuis-induced peripheral blood monocytes model, which may provide a new strategy for preventing the inflammatory disorders induced by H. parasuis.

Intestinal enteroendocrine L cells in amino acid sensing and diseases.

Enteroendocrine L cells are open-type enteroendocrine cells that play an important role in amino acid sensing. They detect amino acids by a number of membrane receptors such as calcium-sensing receptor and G protein coupled receptor family C group 6 subtype A. The receptors activate signaling pathways and trigger cellular electrical activities, inducing gut hormones secretion (glucagon-like peptide 1, glucagon-like peptide 2 and peptide YY). This review focuses on an array of findings on L cells as models, receptors and signaling pathways, electrical activities and hormones secretion in amino acid sensing. Several diseases that are closely related to L cells are also reviewed.

Baicalin modulates NF-κB and NLRP3 inflammasome signaling in porcine aortic vascular endothelial cells Infected by Haemophilus parasuis Causing Glässer's disease.

Haemophilus parasuis (H. parasuis) can cause vascular inflammatory injury, but the molecular basis of this effect remains unclear. In this study,we investigated the effect of the anti-inflammatory, anti-microbial and anti-oxidant agent, baicalin, on the nuclear factor (NF)-κB and NLRP3 inflammasome signaling pathway in pig primary aortic vascular endothelial cells. Activation of the NF-κB and NLRP3 inflammasome signaling pathway was induced in H. parasuis-infected cells. However, baicalin reduced the production of reactive oxygen species, apoptosis, and activation of the NF-κB and NLRP3 inflammasome signaling pathway in infected cells. These results revealed that baicalin can inhibit H. parasuis-induced inflammatory responses in porcine aortic vascular endothelial cells, and may thus offer a novel strategy for controlling and treating H. parasuis infection. Furthermore, the results suggest that piglet primary aortic vascular endothelial cells may provide an experimental model for future studies of H. parasuis infection.

The role of methionine on metabolism, oxidative stress, and diseases.

Methionine is an aliphatic, sulfur-containing, essential amino acid, and a precursor of succinyl-CoA, homocysteine, cysteine, creatine, and carnitine. Recent research has demonstrated that methionine can regulate metabolic processes, the innate immune system, and digestive functioning in mammals. It also intervenes in lipid metabolism, activation of endogenous antioxidant enzymes such as methionine sulfoxide reductase A, and the biosynthesis of glutathione to counteract oxidative stress. In addition, methionine restriction prevents altered methionine/transmethylation metabolism, thereby decreasing DNA damage and carcinogenic processes and possibly preventing arterial, neuropsychiatric, and neurodegenerative diseases. This review focuses on the role of methionine in metabolism, oxidative stress, and related diseases.