Biology subjects

Han, Y.-H.

Publications and source records attributed to Han, Y.-H..

4 recordsLinked to original sources

bioRxiv2024

Discovery of Highly Active Kynureninases for Cancer Immunotherapy through Protein Language Model

Overcoming the immunosuppressive tumor microenvironment is a promising strategy in anticancer therapy. L-kynurenine, a strong immunosuppressive metabolite can be degraded through kynureninases. Through homology searches and protein language models, we identified and then experimentally determined the efficacy of four top-ranked kynureninases. The catalytically most active one nearly doubles turnover number over the prior best, reducing tumor weight by 3.42 times in mouse model comparisons, and thus, presenting substantial therapeutic potential.

cancer biology↗

bioRxiv2023

Albumin-binding recombinant human IL-18BP ameliorates macrophage activation syndrome and atopic dermatitis via direct IL-18 inactivation

Given the clinical success of cytokine blockade in managing diverse inflammatory human conditions, this approach could be exploited for numerous refractory or uncontrolled inflammatory conditions by identifying novel targets for functional blockade. IL-18, a pro-inflammatory cytokine, is relatively underestimated as a therapeutic target, despite accumulated evidence indicating the unique roles of IL-18 in acute and chronic inflammatory conditions, such as macrophage activation syndrome. Herein, we designed a new form of IL-18 blockade, i.e., APB-R3, a long-acting recombinant human IL-18BP linked to human albumin-binding Fab fragment, SL335, for extending half-life. We then explored the pharmacokinetics and pharmacodynamics of APB-R3. In addition to an extended serum half-life, APB-R3 alleviates liver inflammation and splenomegaly in a model of the macrophage activation syndrome induced in IL-18BP knockout mice. Moreover, APB-R3 substantially controlled skin inflammation in a model of atopic dermatitis. Thus, we report APB-R3 as a new potent IL-18 blocking agent that could be applied to treat IL-18-mediated inflammatory diseases.

immunology↗

bioRxiv2020

Intestinal epithelium-derived high density lipoprotein restrains liver injury via the portal vein

Assembly of high density lipoprotein (HDL) requires apoA1 and the cholesterol transporter ABCA1. Although the liver generates most HDL in blood, HDL synthesis also occurs in the small intestine. However, distinct functions for intestinal HDL are unknown. Here we show that HDL in the portal vein, which connects intestine to liver, derivesd mainly from intestine and potently neutralizes lipopolysaccharide (LPS). In a mouse model of short bowel syndrome where liver inflammation and fibrosis was driven by the LPS receptor TLR4, loss of intestine-derived HDL worsened liver injury, whereas liver status was improved by therapeutics that elevated and depended upon intestinal HDL production. Thus, protection of the liver from injury in response to gut-derived signals like LPS is a major function of intestinally synthesized HDL.

immunology↗

bioRxiv2020

Naringenin as an antibacterial reagent controlling of biofilm formation and fatty acid metabolism in MRSA

MRSA is Methicillin-resistant Staphylococcus aureus and they are widespread and making trouble in treatment in communities and surgical areas. MRSA have been adapted to antibiotics so that they can block the access of antibiotics physically or chemically deactivate it or modify the precursor of the target. Flavonoids are secondary metabolites which are naturally produced by plant or fungus and they are acting generally as pigment, quorum sensing molecules, antibiotics to other competitive microorganisms. Their natural origins and multiple activities have drawn much attention to be developed as the potential drugs since flavonoids could be a good candidate to overcome antibiotic resistant bacteria. Among various flavonoids, we found out naringenin has antibacterial activity on MRSA and {Delta}agr mutants which are more resistance than MRSA to beta-lactam antibiotics by decreasing biofilm formation dramatically and decreasing the secretion of fatty acid. It also showed high synergetic activity with oxacillin to both antibacterial activity and biofilm inhibition. Considering the number of flavonoids, our experiments expand the possibility of the use of flavonoids to MRSA.

microbiology↗