generation-monocyte-derived-dendritic-cells-with-differing-sialylated

Generation of Monocyte-Derived Dendritic Cells with Differing Sialylated Phenotypes

Sialic acids are negatively charged monosaccharides typically found at the termini of cell surface glycans. Due to their hydrophilicity and biophysical ...

Albert Einstein College of Medicine

Mouse NOTCH1 carries a highly conserved O-fucose glycan at Thr466 in epidermal growth factor-like repeat 12 (EGF12) of the extracellular domain. O-Fucose at this site has been shown by X-ray crystallography to be recognized by both DLL4 and JAG1 Notch ligands. We previously showed that a Notch1 Thr466Ala mutant exhibits very little ligand-induced NOTCH1 signaling in a reporter assay, whereas a Thr466Ser mutation enables the transfer of O-fucose and reverts the NOTCH1 signaling defect. We subsequently generated a mutant mouse with the Thr466Ala mutation termed Notch1[12f](Notch1). Surprisingly, homozygous Notch1[12f/12f] mutants on a mixed background were viable and fertile.

A modifier in the 129S2/SvPasCrl genome is responsible for the viability of Notch1[12f/12f] mice.

Skin burn injury is the most common cause of trauma that is still considered a dreadful condition in healthcare emergencies around the globe. Due to the availability of a variety of regimes, their management remains a dynamical challenge for the entire medical and paramedical community. Indeed, skin burn injuries are accompanied by a series of several devastating events that lead to sepsis and multiple organ dysfunction syndromes. Hence, the challenge lies in the development of a better understanding as well as clear diagnostic criteria and predictive biomarkers, which are important in their management. Though there are several regimes available in the market, there are still numerous limitations and challenges in the management. In this review article, we have discussed the various biomarkers that could be targeted for managing skin burn injuries. Instead of focusing on allopathic medication that has its adverse events per se, we have discussed the history, ethnopharmacology properties, and prospects of identified phytomedicines from a well-established herbal informatics model. This review article not only discusses the benefits of scrutinized phytocompounds but also the development of novel druggable phyto-compounds to target skin burn injury at a lower cost with no adverse effects.

Medicinal Herbs from Phytoinformatics: An Aid for Skin Burn Management.

The B7/CD28 families of immune checkpoints play vital roles in negatively or positively regulating immune cells in homeostasis and various diseases. Recent basic and clinical studies have revealed novel biology of the B7/CD28 families and new therapeutics for cancer therapy. In this review, we discuss the newly discovered KIR3DL3/TMIGD2/HHLA2 pathways, PD-1/PD-L1 and B7-H3 as metabolic regulators, the glycobiology of PD-1/PD-L1, B7x (B7-H4) and B7-H3, and the recently characterized PD-L1/B7-1 cis-interaction. We also cover the tumor-intrinsic and -extrinsic resistance mechanisms to current anti-PD-1/PD-L1 and anti-CTLA-4 immunotherapies in clinical settings. Finally, we review new immunotherapies targeting B7-H3, B7x, PD-1/PD-L1, and CTLA-4 in current clinical trials.

Recent advancements in the B7/CD28 immune checkpoint families: new biology and clinical therapeutic strategies.

Glycosylation of Notch receptors by O-fucose glycans regulates Notch ligand binding and Notch signaling during hematopoiesis. However, roles in hematopoiesis for other O-glycans that modify Notch receptors have not been determined. Here we show that the EGF domain specific GlcNAc transferase EOGT is required in mice for the optimal production of lymphoid and myeloid cells. The phenotype of  null mice was largely cell-autonomous, and Notch target gene expression was reduced in T cell progenitors. Moreover, EOGT supported residual Notch signaling following conditional deletion of  in hematopoietic stem cells (HSC).  double mutant HSC had more severe defects in bone marrow and in T and B cell development in thymus and spleen, compared to deletion of  alone. The combined results show that EOGT and O-GlcNAc glycans are required for optimal hematopoiesis and T and B cell development, and that they act synergistically with POFUT1 and O-fucose glycans to promote Notch signaling in lymphoid and myeloid differentiation.

Article	Year
A modifier in the 129S2/SvPasCrl genome is responsible for the viability of Notch1[12f/12f] mice. BMC developmental biology\| PubMed ID: 31590629	2019
Medicinal Herbs from Phytoinformatics: An Aid for Skin Burn Management. Current pharmaceutical biotechnology\| PubMed ID: 35272596	2022
Recent advancements in the B7/CD28 immune checkpoint families: new biology and clinical therapeutic strategies. Cellular & molecular immunology\| PubMed ID: 37069229	2023
Synergistic regulation of Notch signaling by different O-glycans promotes hematopoiesis. Frontiers in immunology\| PubMed ID: 37795096	2023

Ankit Tanwar

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