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Background/Aims. Changing gut microbiota is one of the most common causes of host gut inflammation. The active triple peptides, lle-Gln-Trp (IQW) and lle-Arg-Trp (IRW), cause remarkable changes to gut microbiota. The effects of the triple peptides IQW and IRW in gut-damage treatment were explored in this study via an enterotoxigenic Escherichia coli- (ETEC-) induced mouse model. Methods. The mice were randomly distributed into four groups: (a) control (CTRL) group, (b) ETEC group, (c) IQW-ETEC group, and (d) IRW-ETEC group. Villus length and crypt depth were measured after hematoxylin and eosin staining. The inflammatory reaction was analyzed via inflammatory cytokines (i.e., TNF-α, IL-1β, IL-6, and IL-10) using the enzyme-linked immunosorbent assay (ELISA). The microbiota in the colon was sequenced using 16S ribosomal RNA. Results. The villus length decreased, the crypt depth decreased, and the expression of inflammatory cytokines (i.e., TNF-α, IL-1β, IL-6, and IL-10) increased due to ETEC. In the IRW-ETEC and IQW-ETEC groups, the Shannon index decreased ( P < 0.05 ). IQW and IRW increased the abundance of Firmicutes, Proteobacteria, Clostridiales, Lachnospiraceae, and Alloprevotella; contrastingly, it decreased the abundance of Epsilonproteobacteria, Erysipelotrichales, Prevotellaceae, and Flavobacteriaceae compared to the ETEC group (P

The purpose of this study was to explore the regulatory effect of resveratrol (RES) on lipopolysaccharide (LPS)-induced inflammation and its influence on intestinal microorganisms and serum atlas in murine models during the development of inflammation to explore a novel method for the regulation of inflammation. Mice were randomly assigned to three groups: control (CON), LPS, and RES–LPS. The results showed that RES mitigated the inflammatory damage to the intes-tines and liver induced by LPS. Compared with the LPS group, RES treatment decreased the levels of TNF-α, IL-6, IFN-γ, myeloperoxidase, and alanine aminotransferase in the liver. Serum metabolic profile monitoring showed that, compared with the CON group, LPS decreased the levels of five metabolites, including cycloartomunin and glycerol triundecanoate, and increased the levels of eight metabolites, including N-linoleoyl taurine and PE(O-16:0/20:5(5Z), 8Z, 11Z, 14Z, 17Z). Conversely, RES treatment increased the levels of eight metabolites, including pantothenic acid, homovanillic acid, and S-(formylmethyl)glutathione, and reduced seven metabolites, including lysoPE(20:4(8Z,11Z,14Z,17Z)/0:0) and 13-cis-retinoic acid, etc., in comparison with the LPS group. Moreover, RES treatment alleviated the negative effects of LPS on intestinal microbes by reducing, for instance, the relative abundance of Bacteroidetes and Alistipes, and increasing the relative abundance of Lactobacillus. These results suggest that RES has great potential for preventing in-flammation.

Inflammatory bowel disease (IBD) is a chronic lifelong disease characterized by inflammation of the gastrointestinal tract. Although more and more treatment options serve IBD, there is still no cure. It is important to find an effective treatment for IBD. This study aims to investigate whether Lactobacillus plantarum (L. plantarum) could alleviate colitis induced by dextran sulfate sodium (DSS). Following the DSS challenge, L. plantarum on DSS-mediated inflammatory colon lesions in mice, and L. plantarum therapy heightened the relative abundance of the colon-resident Actinobacteria. Analysis of serum metabolomics also indicated that the content of MG (18:4 (6Z, 9Z, 12Z, 15Z)/0:0/0:0) was increased in response to L. plantarum therapy, and this was also the case for indolepyruvate and 1-hydroxyibuprofen. However, 13-oxooctadecadienoic acid (13-oxoODE) and indolylacryloylglycine content fell following the DSS challenge. Based on these results, the study elucidates the mitigatory effects of L. plantarum in colitis, which depend on its regulation of the colonic microbial community and its modification of serum metabolites. The results revealed that L. plantarum mitigated inflammatory colon lesions, reprogrammed the microbial community and altered the level of serum metabolites in a murine model challenged with DSS. The study may present a potential therapeutic strategy for colitis.

Mycobacterium tuberculosis (Mtb) is an intracellular pathogen that can infect and replicate in macrophages. Peptidoglycan (PGN) is a major component of the mycobacterial cell wall and is recognized by host pattern recognition receptors (PRRs). Many bacteria modulate and evade the immune defenses of their hosts through PGN deacetylation. Rv1096 was previously characterized as a PGN N-deacetylase gene in Mtb. However, the underlying mechanism by which Rv1096 regulates host immune defenses during macrophage infection remains unclear. In the present study, we investigated the role of Rv1096 in evading host immunity using a recombinant M. smegmatis expressing exogenous Rv1096 and Rv1096-deleted Mtb strain H37Rv mutant. We found that Rv1096 promoted intracellular bacillary survival and inhibited the inflammatory response in M. smegmatis- or Mtb-infected macrophages. The inhibition of mycobacteria-induced inflammatory response in macrophages was at least partially due to NF-κB and MAPK activation downstream of TLR and NOD signaling pathways. Furthermore, we found that Rv1096 inhibitory effect on inflammatory response was associated with TLR2, TLR4 and NOD2. Finally, we demonstrated the PGN deacetylase activity of Rv1096 by Fourier transform IR and Rv1096 NODB deficient mutant. Our findings suggest that Rv1096 may deacetylate PGNs to evade PRRs recognition, thus protecting Mtb from host immune surveillance and clearance in macrophages.

Background and Objective. Bioactive peptides exert great influence in animals and human health by targeting gastrointestinal tracts. The colitis model of mice was induced by dextran sulfate sodium (DSS). Thirty-two 8-week-old mice weighing 23 g on average were randomly assigned to four groups of 8 each: mice fed basal diet (CON), mice fed basal diet with 5% DSS (DSS), mice fed 0.03% IRW with 5% DSS (IRW-DSS), and mice fed 0.03% IRW with 5% DSS (IQW-DSS). After an adaptation period of 3 days, on day 8, all mice were slaughtered. Serum samples were collected to determine the level of amino acids; colonic tissue was quick-frozen for the determination of gene expression. Methods. The aim of this study was to assess the ability of two kinds of peptides (IRW and IQW) to repair intestinal inflammatory in the DSS-induced model in accordance with serum amino acids and intestinal inflammatory factors. Results. The results demonstrated that the addition of IRW and IQW had a mitigating effect on DSS-induced intestinal inflammation. The level of Asp decreased in the serum of mice supplemented with IRW-DSS (P<0.05), and IQW enhanced the level of Leu, but lowered the level of Ser (P<0.05). IQW and IRW addition reduced the level of TNF-α and IL-17 (P<0.05). No other significant effects were observed. Conclusions. The present study demonstrated that intracolic administration of IRW and IQW might be a novel option for preventing inflammatory bowel disease via regulating the level of serum amino acid and enhancing the intestinal immune defense.

Multi-glycoside of Tripterygium wilfordii Hook. f. (GTW) has been proven to be clinically effective in relieving microinflammation in patients with early diabetic nephropathy (DN). However, the therapeutic mechanisms involved in vivo remain unclear. In the process of early DN, microinflammation and activation of p38 mitogen‑activated protein kinase (MAPK) and canonical nuclear factor (NF)-κB signaling pathways are the important mechanisms by which hyperglycemia contributes to glomerulosclerosis (GS). Therefore, this study aimed to examine the ameliorative effects of GTW on GS, and then to clarify its anti‑microinflammatory mechanisms by inhibiting p38 MAPK and NF-κB signaling activities in the kidney. All rats were divided into 4 groups: the sham group, the sham + GTW group, the vehicle group and the GTW group. The suitable dose of GTW and vehicle were daily administered for 8 weeks after the induction of DN by unilateral nephrectomy combined with intraperitoneal injections of streptozotocin (STZ). The general status of the rats, biochemical parameters, renal histological changes and macrophages in glomeruli, as well as expression of the key proteins in the p38 MAPK and canonical NF-κB signaling pathways and inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-1β and transforming growth factor (TGF)-β1 in the kidney were examined, respectively. The results revealed that, GTW improved the general cond-ition and biochemical parameters of the rats, but did not lower blood glucose; GTW attenuated GS and suppressed glomerular microinflammation including the infiltration of ED1+ cells in glomeruli and the protein overexpression of TNF-α, IL-1β and TGF-β1 in the kidney; GTW inhibited the protein overexpression of key signaling molecules of p38 MAPK and canonical NF-κB pathways in the kidney including phosphorylated p38 MAPK, phosphorylated inhibitor protein IκB and NF-κB (p65). On the whole, we expounded that GTW, as a natural regulator in vivo, alleviates GS without affecting hyperglycemia, by exerting anti-microinflammatory effects, including reducing macrophage infiltration in glomeruli, suppressing TNF-α, IL-1β and TGF-β1 overexpression in the kidney and inhibiting p38 MAPK and NF-κB signaling activities.

Inflammatory cytokines are released by immune cells and are able to induce vascular smooth muscle cells (VSMCs) to undergo apoptosis, causing atherosclerotic plaque rupture. Changes in the expression levels of connexins (Cxs) have been demonstrated in VSMCs to be involved in the pathogenesis of atherosclerotic progression. The present study examined the effect of tumor necrosis factor‑α (TNF‑α) on Cx43 expression levels and apoptosis in human VSMCs. Overexpression of Cx43 plasmids notably stimulated VSMC proliferation. TNF‑α directly inhibited Cx43 expression levels in a dose‑ and time‑dependent manner in VSMCs, however this was blocked by c‑Jun N‑terminal kinase inhibitor. TNF‑α also increased caspase‑3 activity and apoptosis of VSMCs through the inhibition of Cx43. These data suggested that TNF‑α induced the apoptosis of VMSCs and prompted the destabilization of atherosclerotic plaques by downregulating Cx43.

Background Hypericum attenuatum Choisy, a traditional Chinese herb, has been shown to be effective in the treatment of diseases associated with inflammation and has been used to treat rheumatic arthritis in China for centuries. However, the underlying mechanism of its anti-inflammatory effect is poorly understood. Hypothesis/Purpose In this study, we aimed to investigate the anti-inflammatory mechanisms of EtOAc fractions of H. attenuatum Choisy (Ha-EtOAc) on lipopolysaccharide (LPS)-induced RAW264.7 macrophage inflammation and hypothesized that Ha-EtOAc could attenuate inflammation in the colon. Study design LPS was utilized to induce RAW264.7 cells inflammation. The anti-inflammatory effect of Ha-EtOAc in RAW264.7 cells was evaluated by measuring the inhibition ratio of nitric oxide (NO) production. Murine ulcerative colitis (UC) was induced by treatment with 2.5% dextran sulfate sodium (DSS). The basic indexes of the mice, including body weight, food intake and hematochezia, were recorded during mice experiments. Methods The expression levels of pro-inflammatory cytokines, including TNF-α, IL-6 and IL-1β, were measured by quantitative real-time PCR and western blot. Additionally, the influences of Ha-EtOAc on the NF-κB and MAPK signaling pathways were determined by western blot and immunofluorescence assays. In addition, the impact of Ha-EtOAc on gut microbiota of mice with UC was detected by 16S rDNA sequencing. Results Ha-EtOAc inhibited the LPS-induced production of NO and decreased the release of TNF-α, IL-6 and IL-1β in RAW264.7 cells in a dose-dependent manner. In addition, pretreatment with Ha-EtOAc could suppress the nuclear translocation of p65 and the phosphorylation of Erk1/2, p38 and JNK. Ha-EtOAc treatment ameliorated murine UC, as reflected by a reduced body weight loss, improved colon shortening, alleviated mucosal damage and decreased releases of pro-inflammatory cytokines. Furthermore, Ha-EtOAc could modulate the composition of microbial communities. Conclusion Our results demonstrated that Ha-EtOAc exhibited anti-inflammatory effects mainly by suppressing the NF-κB and MAPK pathways, and Ha-EtOAc treatment may be a potent therapy for the treatment of ulcerative colitis.

Objective The purpose of this study was to investigate the effect of Egr2 and Egr4 upregulation on ischemic stroke recovery of rats. Methods In this study, Sprague Dawley (SD) rats assigned at random into control, sham and MCAO (middle cerebral artery occlusion) group were treated accordingly to build MCAO models. The neurological severity scores (NSS) test was applied to assess rats' behavior. Triphenyltetrazolium chloride (TTC) staining reflected infarct areas while Nissl staining revealed the number of neurons. Levels of pro-inflammatory cytokines (interleukin [IL]-1β, IL-6 and tumor necrosis factor [TNF]-α) were judged by enzyme-linked immunosorbent assay (ELISA) in brain and serum tissues. We applied western blot to check the expression of Egr2, Egr4 and JNK/c-JUN (c-Jun N-terminal kinase) pathway. Further grouping of rats were based on various transfection, requiring control, sham, MCAO, MCAO + Egr2 cDNA (complementary DNA), MCAO + Egr4 cDNA, MCAO + Egr2 cDNA + Egr4 cDNA group to observe difference in MCAO recovery and JNK/c-JUN-pathway-related protein expression. Results Under successful modeling of MCAO, western blot results suggested down-regulation of Egr2 and Egr4 and overexpression of pro-inflammatory cytokines. The JNK/c-JUN pathway was activated. On upregulation of Egr2 and Egr4 in infarct areas, neurological function of SD rats recovered along with repressed JNK/c-JUN pathway activation and increased neuron number. Conclusion Upregulation of Egr2 and Egr4 could demote the activation of JNK/c-JUN pathway and the expression of pro-inflammatory cytokines in MCAO rats, so that Egr2 and Egr4 might be potential targets for ischemic stroke in future.

Carbon monoxide (CO), the physiological product of heme oxygenase during catabolic breakdown of heme, has versatile functions and fulfills major anti-oxidative and anti-apoptotic roles in cell systems. Administration of CO is thus thought to be a reasonable therapeutic approach in diseases-such as inflammatory bowel disease-that are induced by reactive oxygen species (ROS). Tricarbonyldichlororuthenium(II) dimer (CORM2) is a commonly used CO donor, but it has poor aqueous solubility and a very short CO-releasing half-life (t1/2). In the present study, we prepared micelles consisting of water-soluble styrene-maleic acid copolymer (SMA) encapsulating CORM2 (SMA/CORM2) that had a hydrodynamic size of 165.3nm. Compared with free CORM2, SMA/CORM2 demonstrated better water solubility (>50mg/ml in a physiological water solution). Moreover, because of micelle formation in an aqueous environment, the CO release rate was slow and sustained. These properties resulted in much longer in vivo bioactivity of SMA/CORM2 compared with that of free CORM2, i.e. the t1/2 in blood of SMA/CORM2 in mice after intravenous (i.v.) injection was about 35 times longer than that of free CORM2. We then evaluated the therapeutic potential of SMA/CORM2 in a murine model of inflammatory colitis induced by dextran sulfate sodium (DSS). Administration (either i.v. or oral) of SMA/CORM2 once at the beginning of colitis, 3days after DSS treatment, significantly improved colitis symptoms-loss of body weight, diarrhea, and hematochezia-as well as histopathological colonic changes-shortening of the colon and necrosis or ulcers in the colonic mucosa. Up-regulation of inflammatory cytokines including monocyte chemotactic protein-1, tumor necrosis factor-α, and interleukin-6 in this DSS-induced colitis was significantly suppressed in SMA/CORM2-treated mice. SMA/CORM2 may thus be a superior CO donor and may be a candidate drug, which involves cytokine suppression, for ROS-related diseases including inflammatory bowel disease.

This study aims to investigate the effects of dietary chitosan (COS) on gastrointestinal pathogen resistance in mice model. For two weeks, a control group of ICR mice received a basal diet whilst the intervention group received the basal diet supplemented with 300 mg/kg COS. After two weeks, the mice fed the supplemented diet had a lower body weight. Then enterotoxigenic Escherichia coli (E. coli) was administered to the mice through oral gavage, with each mouse receiving 108 CFU. At day 7 after infection, the bacterial load in the jejunum and faeces was significantly lower in the COS group than that in the control group. Moreover, the mRNA and protein levels of IL-1β, IL-6, IL-17, IL-18, and TNF-α were significantly lower in the group of mice receiving the COS diet; also the jejunal production of toll-like receptor-4 (TLR-4) was suppressed in the COS group. These results indicate the intervention influenced inflammation and controlled E. coli infection.

Xanthine oxidase (XO) is one of the major enzymes to generate superoxide anion (O2(-)), that is frequently associated with various diseases involving reactive oxygen species (ROS). 4-Amino-6-hydroxypyrazolo[3,4-d]pyrimidine (AHPP) is a potent XO inhibitor showing therapeutic potential for oxidative inflammatory diseases. However its very poor aqueous solubility makes pharmaceutical application difficult. To overcome this drawback, we have successfully synthesized a water soluble polyethylene glycol (PEG) conjugate of AHPP (PEG-AHPP) that exhibited good water solubility, forming micelles in aqueous solution. In the present study, the in vivo pharmacokinetics of this PEG-AHPP was examined. Further its therapeutic potential was investigated in dextran sulfate sodium (DSS) induced mouse colitis model. Compared to parental AHPP, the plasma t1/2 of PEG-AHPP was increased remarkably from 3h to 14h, indicating macromolecular nature of AHPP in circulation. In the DSS induced colitis model, oral administration of 2% DSS in drinking water resulted in the progression of the colitis with diarrhea and hematochezia as well as shortening of the large bowel. Administration of PEG-AHPP intravenously (10mg/kg) or orally (20mg/kg) suppressed pathogenesis significantly; namely diarrhea was reduced markedly, and the length of large bowel returned to almost normal level. Pathological examination clearly revealed improvement of colonic ulcer or necrosis. Production of inflammatory cytokines, i.e., interleukin-6 and tumor necrosis factor (TNF)-α, was significantly increased in DSS-induced colitis mice. However, it was markedly suppressed by PEG-AHPP administration. Similar results were found when serum 8-hydroxydeoxyguanosine (8-OHdG) and thiobarbituric acid reactive substances (TBARS), that are the index of oxidative injury, were measured. PEG-AHPP thus may be a potential candidate drug for ROS-related diseases including inflammatory bowel disease.

Although mesenchymal stem cells (MSCs) are increasingly used to treat graft-versus-host disease (GVHD), their immune regulatory mechanism in the process is elusive. The present study aimed to investigate the curative effect of third-party umbilical cord blood-derived human MSCs (UCB-hMSCs) on GVHD patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and their immune regulatory mechanism. Twenty-four refractory GVHD patients after allo-HSCT were treated with UCB-hMSCs. Immune cells including T lymphocyte subsets, NK cells, Treg cells and dendritic cells (DCs) and cytokines including interleukin-17 (IL-17) and tumor necrosis factor-alpha (TNF-α) were monitored before and after MSCs transfusion. The results showed that the symptoms of GVHD were alleviated significantly without increased relapse of primary disease and transplant-related complications after MSCs transfusion. The number of CD3(+), CD3(+)CD4(+) and CD3(+)CD8(+) cells decreased significantly, and that of NK cells remained unchanged, whereas the number of CD4(+) and CD8(+) Tregs increased and reached a peak at 4 weeks; the number of mature DCs, and the levels of TNF-α and IL-17 decreased and reached a trough at 2 weeks. It was concluded that MSCs ameliorate GVHD and spare GVL effect via immunoregulations.

PDE4 (phosphodiesterase-4) plays a critical role in pathogenesis of allergic asthma and chronic obstructive pulmonary disease (COPD). PDE4 inhibitors are presently under clinical development for the treatment of asthma and/or COPD. Ciclamilast, a new PDE4 inhibitor, is a piclamilast (RP 73401) structural analogue, but has a more potent inhibitory effect on PDE4 and inflammation in the airway tissues and less side effects than that of piclamilast. In this study, we elucidate primarily on the roles of compound on PDE4 enzyme in physiological and pathological processes in a mouse model of asthma. The sensitized/challenged mice were reexposed to ovalbumin and airway response to inhaled methacholine was monitored. Orally administration of ciclamilast, in a dose-dependent manner, significantly inhibited changes in lung resistance and lung dynamic compliance, as well as upregulation of cAMP-PDE activity, increase of PDE4D mRNA expression, but not PDE4B from lung tissue in the murine model. In addition, the compound dose-dependently reduced mRNA expression of eotaxin, tumor necrosis factor (TNF)-alpha and interleukin (IL)-4, but slightly increased mRNA expression of interferon (IFN)-gamma from lung tissue. Further, levels of eotaxin, TNF-alpha and IL-4, and eosinophil and neutrophil accumulation in bronchoalveolar lavage fluid were also significantly reduced. Pathological examination, goblet cell hyperplasia and inflammatory cells infiltration in lung tissue were suppressed by treatment with ciclamilast. A significant correlation was observed between the increases in PDE4D mRNA expression and airway hyperresponsiveness. These studies confirm that inhibitory effect of ciclamilast on airway hyperresponsiveness includes its inhibiting PDE4D mRNA expression, down-modulating PDE4 activity, anti-inflammation and anti-mucus hypersecretion, and ciclamilast may have therapeutic potential for the treatment of asthma.

Oxidative stress is associated with various pathological processes including inflammatory bowel disease, which is a major cause of colon cancer. Here, we examined the antioxidative and anti-inflammatory effects of 4-vinyl-2,6-dimethoxyphenol (canolol), a potent antioxidant compound obtained from crude canola oil. Oral administration of 2% dextran sulfate sodium (DSS) resulted in the progression of colitis with shortening of the large bowel length. Administering a diet containing canolol significantly suppressed pathogenesis; diarrhea markedly improved and the length of large bowel returned to almost normal. Pathological examination clearly revealed improvement of colonic ulcers. Production of inflammatory cytokines, i.e. interleukin-12 and tumor necrosis factor-α, was significantly increased during this pathological process; their production was markedly inhibited by canolol. In the azoxymethane/DSS-induced colon cancer model, mice receiving canolol had a reduced occurrence of cancer, to 60%, compared with control mice, 100% of which had colon cancer. The numbers of tumors in each mouse were also significantly reduced in mice receiving the canolol-containing diet (5.6±2.0) compared with azoxymethane/DSS control mice (10.8±4.2). No apparent toxicity of canolol was observed. Moreover, inflammatory cytokines (i.e. cyclooxygenase-2, inducible nitric oxide synthase and tumor necrosis factor-α) and oxidative responding molecules, i.e. heme oxygenase-1, in colon were suppressed during this treatment. In a mouse colon 26 solid tumor model, canolol significantly suppressed cyclooxygenase-2 expression; however, no significant tumor growth inhibition was observed, suggesting that canolol preferably shows chemopreventive effects during the stages of initiation/promotion. Canolol may, thus, be considered a potential cancer preventive agent or supplement.

Background It has been reported that ischemic postconditioning (IPO) or mesenchymal stem cell (MSC) engraftment could protect organs from ischemia/reperfusion (I/R) injury. We investigated the synergetic effects of combined treatment on lung injury induced by I/R. Methods Adult Sprague-Dawley rats were randomly assigned to one of the following groups: sham-operated control, I/R, IPO, MSC engraftment, and IPO plus MSC engraftment. Lung injury was assessed by arterial blood gas analysis, the wet/dry lung weight ratio, superoxide dismutase level, malondialdehyde content, myeloperoxidase activity, and tissue histologic changes. Cytokine expression was detected using real-time polymerase chain reaction, Western blotting, and enzyme-linked immunosorbent assay. Cell apoptosis was determined by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end assay and annexin V staining. Results MSC engraftment or IPO alone markedly attenuated the lung wet/dry weight ratio, malondialdehyde and myeloperoxidase production, and lung pathologic injury and enhanced arterial partial oxygen pressure, superoxide dismutase content, inhibited pro-inflammatory cytokine levels, and decreased cell apoptosis in lung tissue, compared with the I/R group. In contrast, IPO pretreatment enhanced the protective effects of MSC on I/R-induced lung injury compared with treatment alone. Moreover, in the combined treatment group, the number of MSC engraftments in the lung tissue was increased, associated with enhanced survival of MSCs compared with MSC treatment alone. Additional investigation showed that IPO treatment increased expression of vascular endothelial growth factor and stromal cell-derived factor-1 in I/R lung tissue. Conclusions IPO might contribute to the homing and survival of transplanted MSCs and enhance their therapeutic effects through improvement of the microenvironment of I/R injury.

Porcine circovirus type 2 (PCV2) causes reproductive failure in swine. As glutamine can enhance immune function in animals, this study was conducted with mice to test the hypothesis that dietary glutamine supplementation will improve pregnancy outcome in PCV2-infected dams. Beginning on day 0 of gestation, mice were fed a standard diet supplemented with 1.0% l-glutamine or 1.22% l-alanine (isonitrogenous control). All mice were infected with PCV2 (2000 TCID50) on day 10 of gestation. On day 17 of gestation, six mice from each group were euthanized to obtain maternal tissues and fetuses for hematology and histopathology tests. The remaining mice continued to receive their respective diets supplemented with 1.0% l-glutamine or 1.22% l-alanine through lactation. The PCV2 virus was present in maternal samples (serum and lung) of most mice in the control group but was not detected in the glutamine-supplemented mice. Dietary glutamine supplementation reduced abortion, decreased fetal deaths, and enhanced neonatal survival. The glutamine treatment also reduced concentrations of interleukin-6, while increasing concentrations of tumor necrosis factor-α and C-reactive protein, in the maternal serum of mice. Furthermore, glutamine supplementation attenuated microscopic lesions in maternal tissues (lung, spleen, and liver). Collectively, these results indicate that dietary glutamine supplementation is beneficial for ameliorating reproductive failure in virus-infected mice. The findings support the notion that gestating dams require adequate amounts of dietary glutamine for the optimal survival and growth of embryos, fetuses, and neonates, and have important implications for nutritional support of mammals (including swine and humans) during gestation and lactation.

The present study was performed to determine the protective role of dietary selenium (Se) yeast supplementation in porcine circovirus type 2 (PCV2) infected mice. Forty-eight Kun Ming female mice were randomly assigned to Se yeast group (0.3%Se +basal diet, n = 24) and control group (basal diet, n = 24). After 3 days of adaptive feeding and 15 days treatment with the experimental feed, mice were challenged by intraperitioneal injection of PCV2 at the dosage of 2000 TCID50 (50% tissue culture infection dose, TCID50). Serum total superoxide dismutase (SOD) activity, malondialdehyde (MDA) level, tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP) and interleukin-1 beta (IL-1β) levels were measured at 5, 10, 15, 20 days post infection (dpi). The PCV2 virus load in the liver, spleen and lung, and the microscopic lesions in the liver, spleen and lung also were determined on 5, 10, 15, and 20 dpi. Dietary Se yeast supplementation decreased (Pμ0.05) the serum levels of TNF-α, but had no significant effect on the activity of SOD and the levels of MDA, CRP and IL-1β between experimental and control groups. Dietary Se yeast supplementation had little effect on the PCV2 virus load in the liver, spleen and lung. However, mice in the selenium yeast group showed a significant decrease in microscopic lesion scores in the lung and spleen compared with those in the control group (Pμ0.05). These data indicate Se yeast attenuated the PCV2 infection through altering the systemic inflammation and maintaining the normal organ morphology.