Supplementation of oligosaccharide-based polymer enhanced growth and disease resistance of weaned pigs by modulating intestinal integrity and systemic immunity

Background There is a great demand for antibiotic alternatives to maintain animal health and productivity. The objective of this experiment was to determine the efficacy of dietary supplementation of a blood group A6 type 1 antigen oligosaccharides-based polymer (Coligo) on growth performance, diarrhea severity, intestinal health, and systemic immunity of weaned pigs experimentally infected with an enterotoxigenic Escherichia coli (ETEC), when compared with antibiotics. Results Pigs in antibiotic carbadox or Coligo treatment groups had greater (P < 0.05) body weight on d 5 or d 11 post-inoculation (PI) than pigs in the control group, respectively. Supplementation of antibiotics or Coligo enhanced (P < 0.05) feed efficiency from d 0 to 5 PI and reduced (P < 0.05) frequency of diarrhea throughout the experiment, compared with pigs in the control group. Supplementation of antibiotics reduced (P < 0.05) fecal β-hemolytic coliforms on d 2, 5, and 8 PI. Pigs in antibiotics or Coligo groups had reduced (P < 0.05) neutrophil counts and serum haptoglobin concentration compared to pigs in the control group on d 2 and 5 PI. Pigs in Coligo had reduced (P < 0.05) total coliforms in mesenteric lymph nodes on d 5 and 11 PI, whereas pigs in antibiotics or Coligo groups had reduced (P < 0.05) total coliforms in spleen on d 11 PI compared with pigs in the control group. On d 5 PI, pigs in the Coligo group had greater (P < 0.05) gene expression of ZO1 in jejunal mucosa, but less (P < 0.05) mRNA expression of IL1B, IL6, and TNF in ileal mucosa, in comparison with pigs in the control group. Supplementation of antibiotics enhanced (P < 0.05) the gene expression of OCLN in jejunal mucosa but decreased (P < 0.05) IL1B and IL6 gene expression in ileal mucosa, compared with the control. On d 11 PI, supplementation of antibiotics or Coligo up-regulated (P < 0.05) gene expression of CLDN1 in jejunal mucosa, but Coligo reduced (P < 0.05) IL6 gene expression in ileal mucosa compared to pigs in the control group. Conclusions Supplementation of Coligo improved growth performance, alleviated diarrhea severity, and enhanced gut health in weaned pigs infected with ETEC F18 in a manner similar to in-feed antibiotics.

Intravesical High Dose BCG Tokyo and Low Dose BCG Tokyo with GMCSF+IFN α Induce Systemic Immunity in a Murine Orthotopic Bladder Cancer Model

This study evaluates a short therapy schedule for bladder cancer using BCG Tokyo. BCG Tokyo was evaluated in vitro using bone marrow derived dendritic cells, neutrophils, RAW macrophages and the murine bladder cancer cell line, MB49PSA, and compared to other BCG strains. BCG Tokyo > BCG TICE at inducing cytokine production. In vivo, high dose (1 × 107 colony forming units (cfu)) and low dose (1 × 106 cfu) BCG Tokyo with and without cytokine genes (GMCSF + IFNα) were evaluated in C57BL/6J mice (n = 12–16 per group) with orthotopically implanted MB49PSA cells. Mice were treated with four instillations of cytokine gene therapy and BCG therapy. Both high dose BCG alone and low dose BCG combined with cytokine gene therapy were similarly effective. In the second part the responsive groups, mice (n = 27) were monitored by urinary PSA analysis for a further 7 weeks after therapy cessation. More mice were cured at day 84 than at day 42 confirming activation of the immune system. Cured mice resisted the re-challenge with subcutaneous tumors unlike naïve, age matched mice. Antigen specific T cells recognizing BCG, HY and PSA were identified. Thus, fewer intravesical instillations, with high dose BCG Tokyo or low dose BCG Tokyo with GMCSF + IFNα gene therapy, can induce effective systemic immunity.

Prognostic Value of Lymphocyte-to-Monocyte Ratio for Japanese Patients With Differentiated Thyroid Cancer Treated With Sorafenib Therapy

Background/Aim: We investigated the efficacy and safety of sorafenib in Japanese patients and the prognostic value of systemic immunity markers for predicting clinical outcomes after sorafenib therapy in patients with radioiodine refractory differentiated thyroid cancer (RR-DTC). Patients and Methods: We retrospectively evaluated 26 patients with RR-DTC who underwent sorafenib therapy between July 2014 and December 2020. The systemic immunity markers were calculated from blood cell counts. Results: The median overall survival (OS) was 2,002 days, and the clinical benefit rate was 80.8%. The high lymphocyte-to-monocyte ratio (LMR) group had significantly longer OS than the low LMR group (hazard ratio=0.21; 95% confidence interval=005-0.88; log-rank p=0.019). Adverse events observed in this study were acceptable, and no new safety signals associated with sorafenib were found. Conclusion: Sorafenib therapy is efficacious and safe for Japanese patients with RR-DTC, and baseline LMR may be useful as a sorafenib therapy prognostic marker.

The entomopathogenic fungi Metarhizium brunneum and Beauveria bassiana promote systemic immunity and confer resistance to a broad range of pests and pathogens in tomato

Biocontrol agents can control pathogens by re-enforcing systemic plant resistance through systemic acquired resistance (SAR) or induced systemic resistance (ISR). Trichoderma spp. can activate the plant immune system through ISR, priming molecular mechanisms of defense against pathogens. Entomopathogenic fungi (EPF) can infect a wide range of arthropod pests, and play an important role in reducing pests' population. Here, we investigated the mechanisms by which EPF control plant diseases. We tested two well studied EPF, Metarhizium brunneum isolate Mb7 and Beauveria bassiana as the commercial product Velifer, for their ability to induce systemic immunity and disease resistance against several fungal and bacterial phytopathogens, and their ability to promote plant growth. We compared the activity of these EPF to an established biocontrol agent, T. harzianum T39, a known inducer of systemic plant immunity and broad disease resistance. The three fungal agents were effective against several fungal and bacterial plant pathogens and arthropod pests. Our results indicate that EPF induce systemic plant immunity and disease resistance by activating the plant host defense machinery, as evidenced by increases in reactive oxygen species (ROS) production and defense gene expression, and that EPF promote plant growth. EPF should be considered as control means for Tuta absoluta. We demonstrate that, with some exceptions, biocontrol in tomato can be equally potent by the tested EPF and T. harzianum T39, against both insect pests and plant pathogens. Taken together, our findings suggest that EPF may find use in broad-spectrum pest and disease management and as plant growth promoting agents.

478 Dietary Butyrate and Valerate Glycerides: Effects on Growth and Systemic Immunity of Weanling Piglets Coinfected with F4 and F18 Escherichia coli

Enterotoxigenic Escherichia coli (ETEC) F4 and F18 are the two most dominant pathogenic strains in weaned pigs. The objective of this experiment was to test the effects of dietary monobutyrin and monovalerin on performance and systemic immunity of weanling piglets coinfected with F4/F18 ETEC. Twenty weaned pigs (8.21 ± 1.23 kg) were individually housed and were randomly allotted to one of three diets: control (n = 6), 0.1% monobutyrin (n = 7), or 0.1% monovalerin (n = 7). The experiment was conducted 14 days, including 7 days’ adaption and 7 days post-inoculation (PI). On d 0, d 1, and d 2 PI, pigs were inoculated with 0.5 × 109 CFU/1.5 mL each of F4 and F18 ETEC for three consecutive days. Diarrhea score was recorded daily to determine frequency of diarrhea. Piglets and feeders were weighed throughout the trial to analyze growth performance. Fecal cultures from pigs on d 0, 2, and 4 PI were inspected to identify the absence or presence of hemolytic coliforms. Blood was collected on d 0, 4, and 7 PI for complete blood cells count. All data were analyzed by the Proc Mixed of SAS with randomized complete block design. Pigs supplemented with monovalerin and monobutyrin had numerically higher ADG (249 and 282 g/day) from d 0 to d 7 PI than pigs in control (198 g/day). Supplementation of monovalerin reduced (P &lt; 0.05) frequency of diarrhea throughout the experiment. Pigs fed monovalerin had lower (P &lt; 0.05) neutrophil counts on d 4 PI compared with control. Hemolytic coliforms were observed in all fecal cultures from d 2 and d 4 PI, confirming fecal shedding of ETEC. Results of this study indicate the potential benefits of monovalerin supplementation on performance and disease resistance of weaned pigs coinfected with F4 and F8 ETEC.