Clostridium butyricum Alleviates Enterotoxigenic Escherichia coli K88-Induced Oxidative Damage Through Regulating the p62-Keap1-Nrf2 Signaling Pathway and Remodeling the Cecal Microbial Community.

Clostridium butyricum (CB) can enhance antioxidant capacity and alleviate oxidative damage, but the molecular mechanism by which this occurs remains unclear. This study used enterotoxigenic Escherichia coli (ETEC) K88 as a pathogenic model, and the p62-Keap1-Nrf2 signaling pathway and intestinal microbiota as the starting point to explore the mechanism through which CB alleviates oxidative damage. After pretreatment with CB for 15 d, mice were challenged with ETEC K88 for 24 h. The results suggest that CB pretreatment can dramatically reduce crypt depth (CD) and significantly increase villus height (VH) and VH/CD in the jejunum of ETEC K88-infected mice and relieve morphological lesions of the liver and jejunum. Additionally, compared with ETEC-infected group, pretreatment with 4.4×106 CFU/mL CB can significantly reduce malondialdehyde (MDA) level and dramatically increase superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels in the serum. This pretreatment can also greatly increase the mRNA expression levels of tight junction proteins and genes related to the p62-Keap1-Nrf2 signaling pathway in the liver and jejunum in ETEC K88-infected mice. Meanwhile, 16S rDNA amplicon sequencing revealed that Clostridium disporicum was significantly enriched after ETEC K88 challenge relative to the control group, while Lactobacillus was significantly enriched after 4.4×106 CFU/mL CB treatment. Furthermore, 4.4×106 CFU/mL CB pretreatment increased the short-chain fatty acid (SCFA) contents in the cecum of ETEC K88-infected mice. Moreover, we found that Lachnoclostridium, Roseburia, Lactobacillus, Terrisporobacter, Akkermansia, and Bacteroides are closely related to SCFA contents and oxidative indicators. Taken together, 4.4×106 CFU/mL CB pretreatment can alleviate ETEC K88-induced oxidative damage through activating the p62-Keap1-Nrf2 signaling pathway and remodeling the cecal microbiota community in mice.

Remote Inflammatory Preconditioning Alleviates Lipopolysaccharide-Induced Acute Lung Injury via Inhibition of Intrinsic Apoptosis in Rats.

BACKGROUND: Acute lung injury (ALI) always leads to severe inflammation. As inflammation and oxidative stress are the common pathological basis of endotoxin-induced inflammatory injury and ischemic reperfusion injury (IRI), we speculate that remote ischemic preconditioning (RIPC) can be protective for ALI when used as remote inflammatory preconditioning (RInPC). METHOD: A total of 21 Sprague-Dawley rats were used for the animal experiments. Eighteen rats were equally and randomly divided into the control (NS injection), LPS (LPS injection), and RInPC groups. The RInPC was performed prior to the LPS injection via tourniquet blockage of blood flow to the right hind limb and adopted three cycles of 5 min tying followed by 5 min untying. Animals were sacrificed 24 hours later. There were 2 rats in the LPS group and 1 in the RInPC group who died before the end of the experiment. Supplementary experiments in the LPS and RInPC groups were conducted to ensure that 6 animals in each group reached the end of the experiment. RESULTS: In the present study, we demonstrated that the RInPC significantly attenuated the LPS-induced ALI in rats. Apoptotic cells were reduced significantly by the RInPC, with the simultaneous improvement of apoptosis-related proteins. Reduction of MPO and MDA and increasing of SOD activity were found significantly improved by the RInPC. Increasing of TNF-α, IL-1ß, and IL-6 induced by the LPS was inhibited, while IL-10 was significantly increased by RInPC, compared to the LPS group. CONCLUSION: RInPC could inhibit inflammation and attenuate oxidative stress, thereby reducing intrinsic apoptosis and providing lung protection in the LPS-induced ALI in rats.

Efficacy of ulvan on immune response and immuno-antioxidant gene modulation in Labeo rohita against columnaris disease.

This study reports the effect of ulvan enriched diet on the influence of growth, changes in hemato-biochemical indices, improvement of antioxidant system, enhancement of innate-adaptive immunity and modification of immuno-antioxidant genes expression in Labeo rohita against Flavobacterium columnaris. The weight gain (WG) was significantly high (P > 0.05) in unchallenged normal and challenged fish fed with diets enriched with 25 and 50 mg kg-1 ulvan; the FCR was better (P > 0.05) when fed with 50 mg kg-1 enriched diet. In normal fish fed with or without ulvan supplementation was noted 100% survival rate (SR). In both groups, the red blood cell (RBC) and while blood cell (WBC) counts increased significantly (P > 0.05) when fed with 50 mg kg-1 ulvan diet whereas the hemoglobin (Hb) level increased significantly on being fed with 25 and 50 mg kg-1 ulvan diets. The SOD activity was enhanced significantly in both groups fed with any dose of ulvan diets whereas the MDA and GPx activity increased only with 25 and 50 mg kg-1 ulvan diets. The phagocytic (PC) activity significantly increased with any enriched diet and control diet groups while the respiratory burst (RB) activity increased only with 50 mg kg-1 ulvan diet. The alternate complement pathway (ACP), activity of lysozyme (Lyz), and immunoglobuline M (IgM) were better in both groups fed with 50 mg kg-1 ulvan diet. The SOD and GPx antioxidant gene expression were significantly high in both groups fed with any ulvan diet while the Nrf2 gene expression was high with 50 mg kg-1 ulvan diet. The IL-1ß, TNFα, hepcidin, Lyz, and IgM cytokines or proteins mRNA expression were significant in both groups fed with all ulvan supplement diet whereas the ß-2M expression was significant only with 50 mg kg-1 ulvan diet. The present research indicates that both L. rohita groups fed with 50 mg kg-1 ulvan diet significantly improved growth, antioxidant system, immune defense system, and immuno-antioxidant related gene expression against F. columnaris.

Epitope screening of the major capsid protein within grouper iridovirus of Taiwan and the immunoprotective effect with SWCNTs as the vaccine carrier.

Iridovirus can cause a mass of death in grouper, leading to huge economic loss in recent years. At present, practical vaccine is still the best way to control the outbreak of this virus. Many researches had indicated that the major capsid protein (MCP) of grouper iridovirus of Taiwan (TGIV) is an effective antigen to induce a specific immune response in grouper. However, these traditional vaccines that based on large proteins or whole organisms are faced with challenges because of the unnecessary antigenic load. Thus, in this study, we screened the dominant linear epitope within the MCP of TGIV and then, a new peptide vaccine (P2) was developed via prokaryotic expression system. Furthermore, SWCNTs was used as a vaccine carrier to enhance the immunoprotective effect. To evaluate the immunoprotective effect of this vaccine, a total of 245 fish were vaccinated with P2 (5, 10, 20 mg L-1) and SWCNTs-P2 (5, 10, 20 mg L-1) via immersion before being challenged with live TGIV at 28 days post immunization (d.p.i.). Results showed that the serum antibody titer, enzymatic activity, expression level of some immune-related genes (CC chemokine, IgM and TNF-α) and survival rate were significantly increased (SWCNTs-P2, 20 mg L-1, 100%) compared to the control group (0%). These results indicated that this peptide vaccine could effectively induce specific immune response in vaccinated groupers. Functionalized SWCNTs could serve as a carrier of the peptide vaccine to enhance the immunoprotective effect via immersion. To sum up, epitope screening might be a potential way to develop an effective vaccine nowadays, and SWCNTs might provide a practical method that can be used in large-scale vaccination, especially for juvenile fish, to fight against diseases in aquaculture industry.

Modulating oxidative stress counteracts specific antigen-induced regulatory T-cell apoptosis in mice.

Treg are known to have a central role in orchestrating immune responses, but less is known about the destiny of Treg after being activated by specific Ags. This study aimed to investigate the role of superoxide dismutase, an active molecule in the regulation of oxidative stress in the body, in the prevention of Treg apoptosis induced by specific Ags. Ag-specific Tregs were isolated from the DO11.10 mouse intestine. A food allergy mouse model was developed with ovalbumin as the specific Ag and here, we observed that exposure to specific Ag induced Treg apoptosis through converting the precursor of TGF-ß to its mature form inside the Tregs. Oxidative stress was induced in Tregs upon exposure to specific Ags, in which Smad3 bound the latency-associated peptide to induce its degradation, converting the TGF-ß precursor to its mature form, TGF-ß. Suppressing oxidative stress in Tregs alleviated the specific Ag-induced Treg apoptosis in in vitro experiments and suppressed experimental food allergy by preventing the specific Ag-induced Treg apoptosis in the intestine. In conclusion, exposure to specific Ags induces Treg apoptosis and it can be prevented by upregulating superoxide dismutase or suppressing reactive oxidative species in Tregs.

Macrophage ICAM-1 functions as a regulator of phagocytosis in LPS induced endotoxemia.

OBJECTIVE: Intracellular adhesion molecule-1 (ICAM-1), a transmembrane glycoprotein belonging to the immunoglobulin superfamily, plays a critical role in mediating cell-cell interaction and outside-in cell signaling during the immune response. ICAM-1 is expressed on the cell surface of several cell types including endothelial cells, epithelial cells, leucocytes, fibroblasts, and neutrophils. Despite ICAM-1 has been detected on macrophage, little is known about the function and mechanism of macrophage ICAM-1. METHODS: To investigate the role of lipopolysaccharide (LPS) in ICAM-1 regulation, both the protein and cell surface expression of ICAM-1 were measured. The phagocytosis of macrophage was evaluated by flow cytometry and Confocal microscopy. Small interfering RNA and neutralizing antibody of ICAM-1 were used to assess the effect of ICAM-1 on macrophage phagocytosis. TLR4 gene knockout mouse and cytoplasmic and mitochondrial ROS scavenger were used for the regulation of ICAM-1 expression. ROS was determined using flow cytometry. RESULTS: In this study, we reported that macrophage can be stimulated to increase both the protein and cell surface expression of ICAM-1 by LPS. Macrophage ICAM-1 expression was correlated with enhanced macrophage phagocytosis. We found that using ICAM-1 neutralizing antibody or ICAM-1 silencing to attenuate the function or expression of ICAM-1 could decrease LPS-induced macrophage phagocytosis. Furthermore, we found that knocking out of TLR4 led to inhibited cytoplasmic and mitochondrial ROS production, which in turn, attenuated ICAM-1 expression at both the protein and cell surface levels. CONCLUSION: This study demonstrates that the mechanism of ICAM-1-mediated macrophage phagocytosis is depending on TLR4-mediated ROS production and provides significant light on macrophage ICAM-1 in endotoxemia.

Protective effects of N-acetylcysteine on a chemical-induced murine model of asthma.

INTRODUCTION: Oxidative stress is involved in the pathophysiology of inflammatory airway diseases, including asthma. In this study, we elucidated the possible protective effects of the antioxidant N-acetylcysteine (NAC) on a toluene diisocyanate (TDI)-induced murine asthma model. METHODS: Male BALB/c mice were sensitized and challenged with TDI to generate a chemical-induced asthma model. NAC was given intraperitoneally to mice immediately after each TDI challenge. Airway reactivity to methacholine and bronchoalveolar lavage fluid was analyzed. Lungs were examined by histology. RESULTS: NAC treatment dramatically reduced the increased airway hyperresponsiveness, inflammatory infiltration, and goblet cell metaplasia in TDI-exposed mice. Numbers of total cells, neutrophils, and eosinophils in the bronchoalveolar lavage fluid of TDI-challenged mice were significantly higher than vehicle control, but the administration of NAC decreased these inflammatory cell counts. TDI exposure led to significantly increased levels of interleukin 4 (IL-4) and IL-5, which were also suppressed by NAC. In addition, diminished lung reduced oxidized glutathione ratio and superoxide dismutase activity were observed after TDI challenge, and these changes were attenuated by NAC. CONCLUSION: NAC treatment has beneficial effects in TDI-induced asthma.

Apelin-13 protects the lungs from ischemia-reperfusion injury by attenuating inflammatory and oxidative stress.

Apelin has been reported to regulate mitochondrial function in myocardial ischemia-reperfusion injury and cerebral ischemia-reperfusion injury. However, the role of apelin-13 in lung ischemia-reperfusion injury (LIRI) remains unclear. This study established an experimental rat model to evaluate the underlying mechanisms of apelin-13 on LIRI. Twenty-four rats were randomly divided to sham operation group (group SM), ischemia/reperfusion group (group IR), and apelin-13 treatment group (group APL). The effects of apelin-13 on LIRI were determined histologically using H&E staining, while the wet/dry weight ratio was used to assess lung edema caused by LIRI. Inflammatory cytokines were also detected in Bronchoalveolar lavage (BAL) fluid by ELISA. The protein expression of UCP2 and the morphological changes of mitochondria were determined by western blotting and electromicroscopy, respectively. The results demonstrated the structural damage of lung tissues and lung edema in group IR. An increased level of inflammatory cytokines including IL-1ß, IL-6 and TNF-α was observed in rats with LIRI using ELISA. After that, oxidative stress and morphological damage of mitochondria were also shown in group IR. Yet, the application of apelin-13 reversed all these deleterious effects in group APL. The protective effects of apelin-13 were indicated by decreased reactive oxygen species (ROS) and elevated UCP2 expression levels in rats. In conclusion, this study revealed that apelin-13 had protective effects against LIRI via attenuating lung edema, the production of inflammatory cytokines, oxidative stress and mitochondrial dysfunction.

Endophytic fungus Phomopsis liquidambaris B3 induces rice resistance to RSRD caused by Fusarium proliferatum and promotes plant growth.

BACKGROUND: Rice spikelet rot disease (RSRD) is an emerging disease that significantly reduces rice yield and quality. In this study, we evaluated the potential use of the broad-spectrum endophytic fungus Phomopsis liquidambaris B3 as a biocontrol agent against RSRD. We also compared the control effects of different treatments, including chemical fungicides and treatment with multiple strains and single strains in combination or individually, against RSRD. The objective of this study was to find an effective and environmentally friendly control strategy to reduce the occurrence of RSRD and improve the rice yield. RESULTS: In pot experiments, the effect of B3 alone was better than that of fungicide or combined measures. The results showed that root colonization by B3 significantly reduced the incidence and disease index of RSRD by 41.0% and 53.8%, respectively. This was related to enhanced superoxide dismutase (SOD), peroxidase (POD), and polyphenol oxidase (PPO) activity, and to significantly upregulated expression levels of OsAOX, OsLOX, OsPAL, and OsPR10 in rice. Moreover, B3 improved the diversity of the bacterial community rather than the fungal community in the rice rhizosphere. It also led to a decrease in Fusarium proliferatum colonization and fumonisin content in the grain. Finally, root development was markedly promoted after B3 inoculation, and the yield improved by 48.60%. The result of field experiments showed that the incidence of RSRD and the fumonisin content were observably reduced in rice receiving B3, by 24.41% and 37.87%, respectively. CONCLUSION: The endophytic fungus Phomopsis liquidambaris B3 may become an effective tool to relieve rice spikelet rot disease. © 2020 Society of Chemical Industry.

Multi-Autoantibody Signature and Clinical Outcome in Membranous Nephropathy.

BACKGROUND AND OBJECTIVES: Patients with membranous nephropathy can have circulating autoantibodies against membrane-bound (phospholipase A2 receptor 1 [PLA2R1] and thrombospondin type-1 domain containing 7A [THSD7A]) and intracellular (aldose reductase, SOD2, and α-enolase) podocyte autoantigens. We studied their combined association with clinical outcomes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Serum levels of anti-PLA2R1, anti-THSD7A, anti-aldose reductase, anti-SOD2, and anti-α-enolase autoantibodies were determined in 285 patients at diagnosis and during follow-up using standardized and homemade assays. An eGFR>60 ml/min per 1.73 m2 and remission of proteinuria (<0.3/<3.5 g per d) after 12 months were the outcomes of interest. RESULTS: At diagnosis, 182 (64%), eight (3%), and 95 (33%) patients were anti-PLA2R1+, anti-THSD7A+, and double negative, respectively. The prevalence of a detectable antibody to at least one intracellular antigen was similarly distributed in patients who were anti-PLA2R1+ (n=118, 65%) and double negative (n=64, 67%). Positivity for anti-PLA2R1, anti-SOD2, and anti-α-enolase antibodies and higher titers at diagnosis were associated with poor clinical outcome independently to each other. Combined positivity for anti-PLA2R1, anti-SOD2, and anti-α-enolase was associated with highest risk of poor outcome (odds ratio, 5.5; 95% confidence interval, 1.2 to 24; P=0.01). In Kaplan-Meier analysis, patients who were anti-PLA2R1+/anti-SOD2+ or anti-PLA2R1+/anti-α-enolase+ had lower eGFR at 12 months compared with patients who were anti-PLA2R1+/anti-SOD2- or anti-α-enolase-. Predictive tests (net reclassification index and area under the curve-receiver-operating characteristic analysis) showed that combined assessment of antibodies improved classification of outcome in 22%-34% of cases for partial remission of proteinuria and maintenance of normal eGFR. For patients with nephrotic syndrome at diagnosis, anti-SOD2 positivity and high anti-PLA2R1 titer were associated with a lack of complete remission. Patients who were anti-PLA2R1-/anti-intracellular antigens- had the lowest proteinuria and the highest eGFR at diagnosis and the lowest risk of lower eGFR at 12 months. Epitope spreading was present in 81% of patients who were anti-PLA2R1+ and was associated with increased positivity for intracellular antigens and poor eGFR at diagnosis and 12 months. CONCLUSIONS: Combined serological analysis of autoantibodies targeting membrane-bound and intracellular autoantigens identifies patients with poor clinical outcomes.

Antioxidant and ntiinflammatory efficacy of curcumin on lung tissue in rats with sepsis.

OBJECTIVE: To detect antioxidant and antiinflammatory efficacy of Curcumin (Cur) on lung tissue in rats with sepsis. METHODS: Totally 32 rats were divided into 4 groups; the rats in Group 1 (control group) had abdominal incision under sterile conditions following anesthesia and the abdomen was sutured. Abdominal incision was performed in the rats in Group 2 (Cur group) under sterile conditions following anesthesia and the abdomen was closed. Cur was given to this group after dissolving within dimethylsulphoxide as 100 mg/kg through oral gavage and started for 3 d before surgical procedure. Group 3 (CLP group) had caecal ligation and punction (CLP) under sterile conditions to create sepsis following anesthesia and the abdomen was sutured. CLP was performed in the rats in Group 4 (CLP + Cur group) under sterile conditions following anesthesia to create a sepsis model and the abdomen was closed. Cur was also given to this group after dissolving within dimethylsulphoxide as 100 mg/kg through oral gavage and started for 3 d before surgical procedure. All the rats were sacrificed through blood aspiration from the heart under sterile conditions following anesthesia and lung tissues were removed after 24 h following the surgical procedures. The tissue samples were homogenizated for biochemical analyses; and malondialdehyde (MDA), nitric okxide (NO), myeloperoxidase (MPO), superoxidedysmutase (SOD) nd catalase (CAT) were analyzed through spectrophotometric method, immunhistochemical iNOS staining was performed to assess the inflammation; and histopathological differences between the groups were evaluated. RESULTS: A statistically significant decrease was detected in the CLP + Cur group when compared with the CLP group of which Cur was not given in terms of MDA, MPO and NO levels (P < 0.05) whereas a statistically significant elevation was fpund in the CLP + Cur group when compared with the CLP group in terms of SOD and CAT levels (P < 0.05). CONCLUSION: The study outcomes revealed that supplementation of Cur presents an antioxidant effect by reducing the free radical level and increasing the antioxidant enzyme levels; and an antiinflammatory effect by reducing iNOS level.

Mitogen-Activated Protein Kinase Cascade and Reactive Oxygen Species Metabolism are Involved in Acibenzolar-S-Methyl-Induced Disease Resistance in Apples.

Apple fruits were subjected to dipping treatment to explore the effects of acibenzolar-S-methyl (ASM) and the mitogen-activated protein kinase (MAPK) inhibitor PD98059 on lesion growth in fruits inoculated with Penicillium expansum. We investigated the roles of the MAPK cascade and reactive oxygen species metabolism in disease resistance in apples. ASM treatment inhibited lesion growth; suppressed catalase (CAT) activity; increased H2O2 content; reduced glutathione and ascorbic acid contents; and increased glutathione reductase, ascorbate peroxidase, peroxidase, superoxide dismutase, and NADPH oxidase activities. Moreover, ASM upregulated MdSOD, MdPOD, MdGR, MdAPX, MdMAPK4, MdMAPK2, and MdMAPKK1 expressions and downregulated MdCAT and MdMAPK3 expressions. PD98059 + ASM treatment increased CAT activity and MdCAT and MdMAPK3 expressions; inhibited MdSOD, MdPOD, MdGR, MdAPX, MdMAPK4, MdMAPK2, and MdMAPKK1 expressions; reduced superoxide dismutase, peroxidase, ascorbate peroxidase, and glutathione reductase activities; and reduced glutathione content in apples. These findings indicate that ASM induces disease resistance in apples by regulating the expressions of key genes involved in reactive oxygen species metabolism and the MAPK cascade.

Immunomodulation, antioxidant enhancement and immune genes up-regulation in rainbow trout (Oncorhynchus mykiss) fed on seaweeds included diets.

This study investigated the stimulatory effects of dietary inclusion of Gracilariopsis persica (GP), Hypnea flagelliformis (HF) and Sargassum boveanum (SB) on immune indices, antioxidant capability and immune related genes expression of rainbow trout (Oncorhynchus mykiss). Seven iso-nitrogenous and iso-caloric diets with 0, 5 and 10% of each macroalgae were prepared and fed to rainbow trout juveniles for 83 days. Serum lysozyme (Lyz) and respiratory burst activity (NBT) along with activity of superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT) and expression of LyzII, TNFα and IL-1ß genes in head kidney samples were determined by days 47 and 83. Our results revealed that dietary inclusion of seaweeds improved fish immune status. Long term feeding of fish on seaweed contained diets (except for GP10) improved serum Lyz activity in comparison to control group. Similarly, extended feeding on GP5 and HF10 and HF10 included diets improved SOD and POD levels, respectively. Genes expression studies revealed that seaweeds contained diets noticeably enhanced expression of LyzII, TNFα and IL-1ß in comparison to control fish. However, results revealed that such stimulatory effects were more evident at lower dietary inclusion level and shorter feeding time. In conclusion, the results depicted that dietary inclusion of the seaweeds effectively improved serum immune indices and head kidney antioxidant status and immune related genes expression in a time and dose dependent manner.

Effects of dietary fern (Adiantum capillus-veneris) leaves powder on serum and mucus antioxidant defence, immunological responses, antimicrobial activity and growth performance of common carp (Cyprinus carpio) juveniles.

A 56-day research was performed to examine the influence of graded levels (0 (control), 0.5, 1 and 2%) of Fern (Adiantum capillus-veneris) leaves powder (FLP) in diet on immune competence and growth of common carp (Cyprinus carpio, initial weight = 20 g). The serum total immunoglobulins content and lysozyme activity in the 1 and 2% FLP groups remarkably increased compared to the other groups (P < 0.05). The skin mucosal lysozyme activity enhanced with increasing dietary FLP level in a dose-response manner. Fish fed on the FLP-supplemented diets had higher skin-mucosal superoxide dismutase activity than the control (P < 0.05). However, serum antioxidant enzymes were not affected by dietary fern (P > 0.05). The serum bactericidal activity against human and fish pathogens increased with enhancing the FLP level in diet against Staphylococcus aureus, Escherichia coli (EHEC ATCC 43895), Escherichia coli (CI), Pseudomonas aeruginosa, Klebsiella pneumonia and Aeromonas hydrophila. The serum antibacterial activity against Yersinia ruckeri in the 2% FLP group was higher than the other treatments. Furthermore, the serum bactericidal activity against P. aeruginosa (ATCC 27853) only observed in fish fed on the 1 and 2% FLP-supplemented diets. The skin mucosal bactericidal activity and inhibitory effects increased with enhancing the FLP level in diet against E. coli, K. pneumonia, Y. ruckeri and A. hydrophila in a dose response manner. Moreover, the skin mucosal bactericidal activity against S. aureus only observed in fish fed on 1 and 2% FLP-supplemented diets. The weight gain values in the 1 and 2% FLP groups were higher than the other treatments (P < 0.05). Feed conversion ratio (FCR) improved with increasing FLP level in diet in a dose-response manner (P < 0.05). By considering serum and mucosal bactericidal activities against different pathogenic bacteria, the supplementation of 2% FLP in diet is recommended for C. carpio during grow-out phase.

Effects of N-acetylcysteine on oxidative stress and inflammation reactions in a rat model of allergic rhinitis after PM2.5 exposure.

Particulate matter 2.5 (PM2.5) exposure can increase the prevalence of allergic rhinitis (AR), the mechanism underlying which may include oxidative stress and inflammatory response. As a ROS quenching agent, N-acetylcysteine (NAC) can attenuate the accumulation of inflammatory cells and hyper-responsiveness in animal asthma models. To explore the effect of NAC on the oxidative stress and inflammatory reactions in AR rats exposed to PM2.5, we analyzed the components of PM2.5 and examined the nasal symptoms, redox level in nasal mucosa, Th1/Th2-related serum cytokines, nasal mucosal histopathology and ultrastructure in AR rat models with NAC intervention after PM2.5 exposure. The results showed that the high concentrations of metal cations and PAHs in PM2.5 could aggravate Th2-dominant allergic inflammation in AR model and cause redox imbalance, accompanied by nasal epithelial cell stripping and eosinophil infiltration, while NAC intervention could alleviate the clinical symptoms of AR model after PM2.5 exposure, correct the redox imbalance, reduce the Th2 cytokines, reduce eosinophil infiltration, and promote the moderate regeneration of epithelial cells. The mechanism of NAC reversing PM2.5-mediated action may be related to its anti-oxidant and anti-inflammatory effects, which may provide some new insights for the prevention of AR exacerbated by exposure to PM2.5.

Dried lemon peel enriched diet improves antioxidant activity, immune response and modulates immuno-antioxidant genes in Labeo rohita against Aeromonas sorbia.

The effect of diet enriched with dried lemon (Citrus limon) peel was fed to Labeo rohita at three different levels (0, 1, 2.5, and 5 g kg-1) for a period of 60 days; the impact of the diet on the hematology, antioxidant activity and immunological reaction and gene expression against Aeromonas sorbia is reported. In both un-challenged and challenged groups treated with 2.5 g and 5 g kg-1 dried lemon peel diets, the enhanced significant changes are: the weight gain and specific growth rate, white blood cell and total protein content, the antioxidants: superoxide dismutase, catalase, glutathione peroxidase, and glutathione activities, the respiratory burst, alternative complement pathway, complement C3, and total immunoglobulin M levels. Similarly, the heat shock protein-70 and -90, superoxide dismutase, glutathione peroxidase, glutathione, interleukin-1ß and -8, tumor necrosis factor alpha, inducible nitric oxide synthase, transforming growth factor beta, and immunoglobulin M were up-regulated significantly. Any dried lemon peel enriched diet increased the phagocytic and lysozyme activities significantly in both groups. In the un-challenged group treated with 0 g kg-1 diet or in both groups treated with 2.5 g kg-1 diet the SR was 100%. These results indicate that in both un-challenged and challenged-treated groups the 2.5 and 5 g kg-1 dried lemon peel enriched diets positively modulate growth rate, physiology, and antioxidant status, innate-adaptive immune response as well as antioxidant and immune related gene expression in L. rohita against A. sorbia.

MicroRNA-155 deficiency attenuates inflammation and oxidative stress in experimental autoimmune prostatitis in a TLR4-dependent manner.

To explore the mechanism of microRNA-155 (miR-155) deficiency, protecting against experimental autoimmune prostatitis (EAP) in a toll-like receptor 4 (TLR4)-dependent manner. After wild-type (WT) and miR-155-/- mice were injected with complete Freund's adjuvant and prostate antigen to establish EAP model, half were randomly selected for injection with lipopolysaccharide (LPS, a TLR4 ligand). The following experiments were then performed: von Frey filaments, hematoxylin-eosin (HE) staining, real time quantitative polymerase chain reaction (qRT-PCR), Western blotting, and enzyme-linked immunosorbent assay (ELISA). And the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and the level of Malondialdehyde (MDA) were detected by corresponding kits.miR-155-/- mice with prostatitis exhibited the attenuated pelvic tactile allodynia/hyperalgesia and the suppressed TLR4/nuclear factor-kappa B (NF-κB) pathway as compared with the WT mice with prostatitis. In addition, LPS enhanced the upregulation of miR-155 and the activation of the TLR4/NF-κB pathway in the prostatic tissues of WT mice with EAP. Furthermore, prostatitis mice had aggravated inflammation scores accompanying the increased interleukin (IL)-1ß, tumor necrosis factor-α, IL-6, interferon-γ, IL-12, and MDA in prostatic tissues with the decreased IL-10, SOD and GSH-Px, and the unaltered IL-4. Compared with the mice from the WT + EAP group and the miR-155-/- + EAP + LPS group, mice from the miR-155-/- + EAP group had decreased inflammation and oxidative stress. miR-155 deficiency ameliorated pelvic tactile allodynia/hyperalgesia in EAP mice and improved inflammation and oxidative stress in prostatic tissues in a TLR4-dependent manner involving NF-κB activation, thereby exerting a therapeutic effect in chronic prostatitis treatment.

Celastrol attenuates collagen-induced arthritis via inhibiting oxidative stress in rats.

The present work aimed to investigate the anti-rheumatism effect and the mechanism of celastrol in collagen-induced arthritis (CIA) rats. The CIA model was established in male Wistar rats by intradermal injection of bovine collagen-II in complete Freund's adjuvant (CFA) at the base of tail. The rats received oral administration of celastrol for 28 days. A variety of indicators, including paw swelling and arthritis scores, were measured for anti-rheumatism effect. Celastrol treatment attenuated paw swelling and arthritis scores in CIA rats. Celastrol improved the spleen and thymus indexes in CIA rats. The increased levels of inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, and interferon (IFN)-γ, were abolished by celastrol treatment. In addition, the weakened superoxide dismutase (SOD) activity, the increased levels of malondialdehyde (MDA), and superoxide anions, and enhanced NADPH oxidase (Nox) activity were all reversed by celastrol treatment. Nox4 overexpression reversed the attenuating effects of celastrol on paw swelling and arthritis scores in CIA rats. The celastrol-induced improvement in spleen and thymus indexes in CIA rats was inhibited by Nox4 overexpression. Nox4 overexpression reversed the abolishing effects of celastrol on the increases of TNF-α, IL-1ß, IL-6, and IFN-γ levels in the serum of CIA rats. These results demonstrated that celastrol improved rheumatism in arthritis via inhibiting oxidative stress.

Influence of the lumpy skin disease virus (LSDV) superoxide dismutase homologue on host transcriptional activity, apoptosis and histopathology.

Lumpy skin disease virus (LSDV), a Capripoxvirus, is of economic importance in the cattle industry and is controlled by vaccination. A comparison was made of the host response to the two LSDV vaccines Neethling and Herbivac LS, with reference to the well-studied Orthopoxvirus, modified vaccinia Ankara (MVA), in a mouse model. Because the vaccines differ at the superoxide dismutase homologue (SOD) gene locus, recombinant SOD knock-out and knock-in nLSDV vaccines were constructed and all four vaccines were tested for the induction and inhibition of apoptosis. The SOD homologue was associated both with induction of apoptosis as well as inhibition of camptothecin-induced apoptosis. Histological analysis of chorioallantoic membranes of fertilized hens' eggs infected with the four different vaccines indicated marked mesodermal proliferation associated with vaccines containing the full-length SOD homologue as well as increased immune cell infiltration. Our findings suggest that the SOD homologue may influence vaccine immunogenicity.