Potassium diformate in the diet of sterlet sturgeon ( Acipenser ruthenus ): Zootechnical performance, humoral and skin mucosal immune responses, growth‐related gene expression and intestine morphology

2021 ◽  
Author(s):  
Mansore Kakavand ◽  
Seyed Pezhman Hosseini Shekarabi ◽  
Mehdi Shamsaie Mehrgan ◽  
Houman Rajabi Islami
2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A612-A612
Author(s):  
Yoshinori Narita ◽  
Mika Kamata-Sakurai

BackgroundAgonistic antibodies targeting CD137 in clinic have failed due to severe hepatotoxicity, leading to the development of bispecific approaches that must rely on high tumor-associated antigen expression to crosslink CD137. Here we report on STA551, a novel anti-CD137 agonist antibody which binds to CD137 only in the presence of ATP. Extracellular ATP concentration is well-known to be elevated in tumor tissue while remaining tightly regulated in non-tumor tissue, suggesting that STA551 can activate immune cells only in tumor tissue and not elsewhere. Thus, STA551 has great potential to overcome the limitations of conventional CD137-targeted antibodies.MethodsWe evaluated in vitro STA551’s effect on IFN-γ production from human CD8+ T cells. We also evaluated in vivo STA551’s effect on tumor growth, RNAseq-based immune-related gene expression, immunohistochemistry, and T cell activation in tumor and non-tumor tissues in human CD137 knock-in mice treated with mouse surrogate STA551 (Sta-MB) or urelumab (Ure-MB) in combination with anti-PD-L1 antibody.ResultsIn a human T cell assay, STA551 induced IFN-γ only in the presence of ATP. In contrast, urelumab induced IFN-γ regardless of ATP concentration. In mice with Colon 38 tumors, Sta-MB inhibited tumor growth at least as strongly as Ure-MB, but whereas Ure-MB elicited systemic immune responses in draining lymph node, spleen, and liver, Sta-MB appeared to evade such responses. To confirm immune responses in tumors, we evaluated immune-related gene expression and found changes after treatment with Sta-MB or Ure-MB. These results suggest that STA551 works only in tumor tissue. Furthermore, Sta-MB with anti-PD-L1 antibody synergistically inhibited tumor growth and dramatically changed immune-related gene expression, CD8+ T cell infiltration, and PD-L1 expression without systemic immune responses. Also, it was well-tolerated in cynomolgus monkey in a repeated-dose toxicity study*.ConclusionsSTA551 is a novel anti-CD137 agonist antibody that exerts agonistic activity selectively in tumors without on-target toxicity in non-tumor tissues, regardless of tumor-associated antigen expression. These results strongly support the clinical testing of STA551 for the treatment of solid tumors. STA551 is currently being tested in a phase 1 clinical study.Ethics ApprovalAll animal studies were reviewed and approved by the Institutional Animal Care and Use Committee (IACUC).


Antibiotics ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 37
Author(s):  
Xinyi Wang ◽  
Baoliang Liu ◽  
Xiaoqiang Gao ◽  
Xi Wang ◽  
Hongxu Li ◽  
...  

UVA is the most common type of solar UV radiation in aquatic environments; however, the effects it causes in shrimp farming in recirculating water systems (RAS) is unclear. Thus, the growth performance, immune responses, antioxidant status and apoptosis-related gene expression in Pacific white shrimp, Penaeus vannamei (body weight 9.56 ± 0.10 g), reared with 12L: 12D full spectrum light as background light under five UVA (peak at 400 nm) photoperiods (0L: 24D, 2L: 22D, 4L: 20D, 8L: 16D and 12L: 12D) at a light intensity of 1 W/m2 were investigated. The results showed that the 2L: 22D and 4L: 20D UVA photoperiods enhanced the growth performance and reduced the feed conversion ratio and the shrimp mortality. Shrimp exposed to UVA (2L: 22D and 4L: 20D) also displayed higher levels of hepatopancreas catalase (CAT), superoxide dismutase (SOD), acid phosphatase (ACP), phenol oxidase (PO) and lysozyme (LZM) compared to the 8L: 16D and 12L: 12D groups. The malondialdehyde (MDA) levels increased in line with the extension of the UVA irradiation time. The mRNA expression of apoptosis-related genes in all the UVA treatments were significantly higher than with the control treatment, except for the 2L: 22D group. The results of the 2L: 22D and 4L: 20D treatments were significantly higher than those of the control group, except for LGBP. In conclusion, 2L: 22D and 4L: 20D UVA photoperiods increased growth performance and decreased FCR, improved the innate immunity and antioxidant response and reduced the mortality rate in adult shrimp.


2005 ◽  
Vol 85 (1) ◽  
pp. 13-22 ◽  
Author(s):  
Palok Aich ◽  
Heather L Wilson ◽  
Neil A. Rawlyk ◽  
Shakiba Jalal ◽  
Radhey S Kaushik ◽  
...  

The surgical preparation of multiple, sterile intestinal “loops” has provided an effective model for the analysis of vaccine-induced mucosal immune responses in ruminants. The objective of the present investigation was to evaluate intestinal “loops” as a model for genomic analyses of mucosal immune responses. Immunohistochemistry revealed no significant changes in mucosal epithelial cell architecture but microarray analyses were completed to determine if surgery and elimination of microflora significantly altered gene expression in the small intestine of one month-old calves. RNA was isolated from intestinal “loops” (Sample) and adjacent, intact intestine (Control) of each animal at 48 h (n = 3) and 12 d (n = 3) postsurgery. Total RNA from control and sample tissues was hybridized on Pyxis Genomics bovine cDNA microarrays (7884 ESTs) to identify differentially expressed genes. We observed only 2.3% (180/7884) of ESTs were significantly and differentially changed in expression at 48 h post-surgery and approximately 80% (143/180) of these genes were up-regulated. A subset of these differentially expressed genes was validated by quantitative Real Time PCR and these analyses demonstrated that many genes were returning to baseline expression levels at 12 d post-surgery. Notable among differentially expressed genes were gene clusters involved in apoptosis, cell cycle, and cell differentiation. Surgery and elimination of microflora in 1-mo-old calves significantly altered the expression of a relatively minor number of genes but these genes were implicated in important aspects of normal mucosal function. Therefore, intestinal “loops” that control for the effects of surgical manipulation and commensal microflora must be included when conducting mucosal gene expression analyses within this animal model. Key words: Bovine, Cy-dye fluorescence, immunohistochemistry, intestine, microarray, microflora, resonance light scattering, qRT-PCR


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