The transcriptome sequencing analysis reveals immune mechanisms of soybean fermented powder on the loach (Misgurnus anguillicaudatus) in response to Lipopolysaccharide (LPS) infection

The loach (Misgurnus anguillicaudatus), a small commercial fish that is widely cultivated for its high-quality protein, vitamins, minerals, and essential amino acid, is a member of the genus Misgurnus and the family Cyprinidae. In this study, we gave the LPS-injected loach fermented soybean meal and used transcriptome sequencing to investigate the impact of the fermented soybean powder on the loach’s immune system. 3384 up-regulated genes and 12116 down-regulated genes were found among the 15500 differentially expressed genes, according to the results. The differentially expressed genes were shown to be involved in cellular processes, metabolic processes, cellular anatomical entities, and binding, according to the Go functional annotation. Meanwhile, the KEGG enrichment analysis indicated that the soybean fermented powder treated groups showed significant differences in DNA replication, Nucleotide excision repair, Fanconi anemia pathway, and Base excision repair pathways, suggesting that these pathways are closely related to the enhancement of the immune function of loach by soybean fermented powder. The particular conclusions not exclusively can provide a new conception for the rational utilization of soybean fermented powder but also can provide theoretical guidance for the subsequent healthy breeding of loach

BECN1-dependent CASP2 incomplete autophagy induction by binding to rabies virus phosphoprotein

Autophagy is an essential component of host immunity and used by viruses for survival. However, the autophagy signaling pathways involved in virus replication are poorly documented. Here, we observed that rabies virus (RABV) infection triggered intracellular autophagosome accumulation and results in incomplete autophagy by inhibiting autophagy flux. Subsequently, we found that RABV infection induced the reduction of CASP2/caspase 2 and the activation of AMP-activated protein kinase (AMPK)-AKT-MTOR (mechanistic target of rapamycin) and AMPK-MAPK (mitogen-activated protein kinase) pathways. Further investigation revealed that BECN1/Beclin 1 binding to viral phosphoprotein (P) induced an incomplete autophagy via activating the pathways CASP2-AMPK-AKT-MTOR and CASP2-AMPK-MAPK by decreasing CASP2. Taken together, our data first reveals a crosstalk of BECN1 and CASP2-dependent autophagy pathways by RABV infection

Additional file 1 of A humanized 4-1BB-targeting agonistic antibody exerts potent antitumor activity in colorectal cancer without systemic toxicity

Additional file 1: Fig. S1 The interaction model between 4-1BB and HuB6 Fab. One copy of the complex is composed of chain A and chain E and F. Chain D interacts with chain B’ and C’ in another asymmetric unit form another copy with the same mode as chain B and C. 4-1BB is in blue and orange, HuB6 Fab H chain is in red, green, cyan and magenta. 4-1BB and HuB6 Fab in another asymmetric unit are in grey. Fig. S2 The dependence on FcγR of the 4-1BB agonist activity. CD8 + T cells were cocultured with CHO-K1 cells expressing different FcγRs and treated with HuB6, utomilumab, urelumab or IgG control for 3 days in a CO2 incubator at 37 °C. After incubation, the secreted IFN-γ and IL-2 levels in the cell supernatants were determined by ELISA. Fig. S3 Tumor photos of the MC38 and CT26 model mice. a the tumors of MC38 and CT26 model mice treated with the three doses of HuB6. b the tumors of MC38 and CT26 model mice treated with the three 4-1BB agonistic mAbs. Fig. S4 Hematoxylin and eosin staining for major organs of the mice treated with HuB6. Major organs included heart, liver, lung, kidney and spleen

BECN1-dependent CASP2 incomplete autophagy induction by binding to rabies virus phosphoprotein

<p>Autophagy is an essential component of host immunity and used by viruses for survival. However, the autophagy signaling pathways involved in virus replication are poorly documented. Here, we observed that rabies virus (RABV) infection triggered intracellular autophagosome accumulation and results in incomplete autophagy by inhibiting autophagy flux. Subsequently, we found that RABV infection induced the reduction of CASP2/caspase 2 and the activation of AMP-activated protein kinase (AMPK)-AKT-MTOR (mechanistic target of rapamycin) and AMPK-MAPK (mitogen-activated protein kinase) pathways. Further investigation revealed that BECN1/Beclin 1 binding to viral phosphoprotein (P) induced an incomplete autophagy via activating the pathways CASP2-AMPK-AKT-MTOR and CASP2-AMPK-MAPK by decreasing CASP2. Taken together, our data first reveals a crosstalk of BECN1 and CASP2-dependent autophagy pathways by RABV infection.</p