China
Africa
Explore chapters and articles related to this topic
The Development of Improved Therapeutics through a Glycan- “Designer” Approach
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Another very important glycan detecting receptor family that need consideration when designing a glycotherapeutic are Siglec receptors (Sialic acid-binding Ig-like lectins). Siglecs are lectins receptors expressed mostly on the cells of the immune system. Siglecs bind and recognize different glycans made of sialic acids. Until now there are 16 human Siglec receptors described (Schnaar, 2016). Not all of Siglec’s functions are known; however, ongoing research shows that Siglec-1 is able to recognize pathogenic sialic acids and drive the inflammatory immune response. Other CD33-related Siglecs are associated with tyrosine-activation pathway of the immune cells. Many human pathogens mimic sialic acids and utilize Siglec receptor for their advantage.
Stem-Cell-Specific Aptamers for Targeted Cancer Therapy
Published in Rakesh N. Veedu, Aptamers, 2017
Hadi Al. Shamaileh, Dongxi Xiang, Tao Wang, Wang Yin, Wei Duan, Sarah Shigdar
Aptamers for acute myelogenous leukemia (AML) were developed with cell-SELEX on NB4 cells derived from AML M3 to generate DNA aptamers [125]. Out of 10 candidate aptamers, 3 were found to have high binding affinities to NB4 cells with Kd′ values of 2.77 nM for JH6, 7.57 nM for JH19, and 12.37 nM for K19. The selected aptamers (JH6, JH19, and K19) showed no binding to lymphocytes, but they did show binding on mature and immature granulocytes and monocytes. These results suggest that the aptamers may recognize myeloid-specific surface markers. Additionally, the aptamers had low, but statistically significant, levels of binding to CD34(+) early hematopoietic precursors. The binding of the aptamers was abolished when NB4 cells were treated with trypsin to remove cell surface markers, indicating that the target molecules of the aptamers may be directly or indirectly related to surface proteins on the cell membrane. It was later confirmed that the likely binding target of the aptamer K19 is siglic-5, and it was capable of competing with anti-Siglec-5 antibody for binding to NB4 cells. Siglec-5 has been reported to be expressed on granulocytes and therefore can be used as a biomarker for granulocytic maturation and AML cell detection and can potentially mediate targeted therapy against AML cells [125, 155]. In the study, the researchers conjugated a biotin-labeled K19 aptamer with streptavidin-labeled saporin, and it was found that the aptamer mediated the uptake of saporin and inhibited NB4 cell proliferation in vitro.
Traffic-related particulate matter aggravates ocular allergic inflammation by mediating dendritic cell maturation
Published in Journal of Toxicology and Environmental Health, Part A, 2021
Moonwon Hwang, Sehyun Han, Jeong-Won Seo, Ki-Joon Jeon, Hyun Soo Lee
This procedure has been described previously by Lee et al. (2015); 20 min after topical OVA eye drop, the ipsilateral conjunctivae were collected from euthanized mice. Conjunctival tissues digestion was performed with 0.05 mg/ml DNase I (Hoffmann-La Roche) and 2 mg/ml collagenase (Hoffmann-La Roche, Basel, Switzerland) for 90 min at 37°C. Cells were suspended in 0.5% bovine serum albumin buffer with anti-FcR (CD16/CD32, BioLegend) antibodies to block Fc responses. Cells were then stained with a phycoerythrin-cyanin dye 7 (PE-Cy7)–conjugated anti-c-kit antibody (clone 2B8, BioLegend), a FITC–conjugated anti-CD45 antibody (clone 30-F11, BioLegend), and a PE-conjugated sialic acid binding immunoglobulin-type lectin-F antibody (Siglec-F; clone E50-2440, BD Biosciences). The isotype control was stained with related matched antibodies (BioLegend). All samples were analyzed utilizing a BD LSRFortessa flow cytometer (BD Biosciences).
PEGylated liposomes: immunological responses
Published in Science and Technology of Advanced Materials, 2019
Marwa Mohamed, Amr S. Abu Lila, Taro Shimizu, Eman Alaaeldin, Amal Hussein, Hatem A. Sarhan, Janos Szebeni, Tatsuhiro Ishida
Insertion of gangliosides from a porcine brain (oligoglycosylceramides; a mixture of GM1, GD1a, GD1b and GT1b, containing sialic acid) into PEGylated liposomes at a concentration of 10% of the total phospholipids also shows activity in reducing the ABC effect [112]. This is attributed to the immunosuppressive effect of gangliosides, functioning as Siglec ligands (lectin-like adhesion proteins on macrophages) on reactive B cells that result in B cell tolerance and decreased anti-PEG IgM production. Accordingly, liposomal membrane modification with clinically acceptable gangliosides might be worth exploring further.