At present, radiotherapy (RT) still acquires limited success in clinical due to the lessened DNA damage under hypoxia and acquired immune tolerance owing to the amplified programmed death ligand‐1 (PD‐L1) expression. Incredibly, intracellular PD‐L1 expression depression is proven to better sensitize RT by inhibiting DNA damage repair. However, the disability of the clinically used antibodies in disrupting the extracellular PD‐L1function still limits the effectiveness of radio‐immunotherapy. Therefore, better PD‐L1 regulation strategies are still urgently needed to better sensitize radio‐immunotherapy. Hence, for this purpose, TPP‐LND is synthesized by linking mitochondrial‐targeted triphenylphosphine cations (TPP+) to the antineoplastic agent lonidamine (LND), which significantly reduces the dose needed for LND to induce effective oxidative phosphorylation inhibition (2 vs 300 µM). Then, TPP‐LND is wrapped with liposomes to form TPP‐LND@Lip nanoparticles. By doing this, TPP‐LND@Lip nanoparticles can sensitize RT by reversing the hypoxic microenvironment of tumors to generate more DNA damage and reducing the expression of PD‐L1 via enhancing the adenosine 5′‐monophosphate‐activated protein kinase activation. As expected, these well‐designed economical TPP‐LND@Lip nanoparticles are more effective than conventional anti‐PD‐L1 antibodies to some extent.
The purpose of this study was to determine the effect of Angelica sinensis polysaccharide (ASP) supplemented in diet on the innate cellular immune response and disease resistance in grouper, Epinephelus malabaricus. Fish were fed diets containing different doses of ASP (0, 500 and 3,000 mg kg -1 diet) for 12 weeks. After 12 week feeding, the respiratory burst activity, phagocytic activity, and leukocytes proliferation in head kidney were assayed. The functional immunity in terms of cumulative mortality was also assessed by a challenge with live Edwardsiella tarda. Results showed that the respiratory burst activities in ASP-supplemented groups were increased significantly. The respiratory burst index was the highest in fish-fed 3000 mg kg -1 diet and the lowest in control. The phagocytic activities in ASP-supplemented groups were significantly higher than that of control. No significant difference in phagocytic activity was observed between ASP-supplemented groups. ASP stimulated the head kidney leukocytes proliferation significantly, despite the absence of lipopolysaccharide (LPS) or not. The cumulative mortalities of fish fed with 3000 mg ASP kg -1 diet were significantly lower than those fed with 500 mg ASP kg -1 diet and control diet after 96 h of challenge. In conclusion, dietary ASP enhanced some cellular immune parameters and disease resistance against E. tarda in grouper.
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