Category: Technology

A group from Taipei Medical University, Taiwan, etc. has reported that Galectin-3 could be a good marker for Abdominal Aortic Aneurysm (AAA).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200414/

Although ultrasound is the gold standard for the diagnosis and surveillance of AAAs with high sensitivity and specificity, the frequency of ultrasound surveillance varies with aneurysm diameter. Furthermore, ultrasound is not recommended for patients with subaneurysmal aortic dilatation. Therefore, circulating biomarkers of inflammation, which reflect the aneurysmal size, can assist in the detection and prognosis of AAA.

A cross-sectional study was performed to analyze plasma Gal-3 and IL-6 levels as circulating biomarkers in both control patients (n = 195) and patients with AAA (n = 151). Plasma Gal-3 levels were significantly higher in patients with AAA than in control patients (96.9 ± 4.5L vs. 76.5 ± 1.9 ng/mL), and the levels of IL-6 were also higher in AAA samples than in healthy control samples (92.8 ± 5.2 pg/mL vs. 72.5 ± 3.0 pg/mL). The diagnostic performance of Gal-3 and IL-6 were evaluated using ROC analysis. The results were that Gal-3 levels predicted AAA presence (AUC=0.91) significantly more accurately than did IL-6 levels (AUC=0.72).

Gal-3 is likely a chemotactic molecule for macrophages. Thus, its expression could be associated with various cardiovascular diseases. The increased risk of AAA observed in patients with higher Gal-3 levels may reflect the recruitment of inflammatory cells, including activated macrophages, in the arterial system and the subsequent secretion of Gal-3.

A group from Tohoku Medical and Pharmaceutical University has reviewed 11 kinds of mammalian lectins responsible for pathogen recognition.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185196/

From this review, three C-type lectins were highlighted here for your information.
Many C-type lectins show selectivity toward mannose residues and this mannose binding is utilized for microbe sensing. One of the most studied examples is mannose-binding protein, MBP, which is known to activate the complement lectin pathway. Why does mannose recognition play this role in detecting non-self when mannose residues occur frequently in mammalian N-glycans, e.g., high-mannose glycan. The likely explanation is in the higher spatial density of mannose residues on bacteria relative to that of mammalian glycans. The C-type lectin domain has a Ca2+ ion coordinated with the OH3 and OH4 of the mannose. The affinity of 1:1 binding is weak with a dissociation constant of roughly 1 mM, however, the presentation of trimeric binding sites in MBP domains could interact with the multiple terminal mannose residues presented on microbes. The spacing between the mannose binding sites is around 50 Å, and is eminently suitable for binding packed terminal mannose residues with high affinity, but not single endogenous high mannose glycans. Langerin is also a C-type lectin with a coiled-coil region and a neck region in a trimeric structure, and has a distance of roughly 40 Å between binding sites. A trimeric oligosaccharide ligand with appropriate linker length for the 40 Å distance between each binding site has been reported for Langerin, with 1,000-fold higher affinity over the monomeric ligand.

As for Dectin-2, the binding site accommodates internally positioned Manα1-2Man of mannans and other polysaccharides, whereas other C-type lectins like DC-SIGN and langerin bind only terminal Manα1-2Man structures. Recognition of internal mannose residue is advantageous in that multiple binding sites are presented toward lectin receptor. Dectin-2 is thus suitable for binding to longer mannan polysaccharides.

A group from Cliniques universitaires Saint-Luc, Belgium, etc. has reported relationship between serum uric acid level and COVID-19 severity.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201458/

The prevalence of hypouricemia is approximately 0.3% in the general ambulatory population. In this study, 20% of the patients hospitalized for SARS-CoV-2 infection developed hypouricemia, a proportion that increased to 77% among patients requiring mechanical ventilation.

Uric acid is the end-product of purine metabolism in humans and is generated in the liver. The kidney is an important regulator of circulating uric acid levels as it excretes most of total body uric acid. Serum urate is freely filtered by the glomeruli followed by a complex balance of reabsorption and secretion in the kidney proximal tubule. Although the molecular mechanisms of urate transport in the proximal tubule are still incompletely understood, URAT1 (SLC22A12) is the main apical transporter mediating urate reabsorption in the brush border of the proximal tubule. In a small subset of kidney samples from patients who died from COVID-19, it was shown that life-threatening SARS-CoV-2 infection is associated with a significant (~ 70%) decrease in the expression of the apical urate transporter URAT1 in the kidney proximal tubule, contributing to the impaired tubular absorption of urate. The mechanisms linking hypouricemia and progression to severe disease requiring mechanical ventilation in patients with COVID-19 remains speculative and may be diverse

Anyhow, it seems that serum uric acid could be used as a reliable biomarker to identify patients at risk of life-threatening COVID-19.

A group from University of British Columbia, Canada has reported whether HIV antibodies could neutralize SARS-CoV-2 or not.
https://www.nature.com/articles/s41598-021-91746-7

Cross-reactive interactions of three HIV antibodies (2G12, PGT128, PGT126) in the presence of methyl α-d-mannopyranoside, a stabilized mannose analogue, were evaluated using an ELISA assay. Disruption of cross-reactivity was observed for all these antibodies with increasing concentrations of methyl α-d-mannopyranoside, demonstrating that the binding of these antibodies to SARS-CoV-2 were via glycan sensitivity of these interactions.

HEK293-T cells stably overexpressing ACE-2 were incubated with SARS-CoV-2 S pseudo-typed virus harbouring a luciferase reporter gene, in the presence of serial dilutions of three HIV antibodies. Luciferase activities in cellular lysates were determined 48 h post-infection (RLU: relative luciferase units). However, no neutralization capabilities were detected for these antibodies over a wide range of concentrations, while VH-FC ab8 demonstrated potent neutralization, a positive control antibody VH-FC ab8 which targets the SARS-CoV-2 RBD.

But, the blog admin thinks that the infection to immune cells (i.e., macrophages) expressing C-type lectins might be neutralized by these HIV antibodies? 

A group from Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, etc. has reported new urinary biomarkers for cardiovascular events originating from Type 2 diabetes.
https://www.frontiersin.org/articles/10.3389/fcvm.2021.668059/full

Targeting cardiovascular events (CVE) as one of primary outcomes originating from the diabetes, urinary glycomes in 680 patients with type 2 diabetes were evaluated with using Lectin microarrays.

During approximately a 5-year follow-up period, 62 patients reached the endpoint. Cox proportional hazards analysis revealed that urinary glycan signals binding to two lectins were significantly associated with the outcome after adjustment for known indicators of CVE and for false discovery rate, as well as increased model fitness. Hazard ratios for these lectins (+1 SD for the glycan index) were UDA (recognizing glycan: mixture of Man5 to Man9): 1.78 (95% CI: 1.24–2.55, P = 0.002) and Calsepa [High-Man (Man2–6)]: 1.56 (1.19–2.04, P = 0.001). Common glycan binding to these lectins was high-mannose type of N-glycans.

The urinary excretion of high-mannose glycan may be a valuable biomarker for improving prediction of CVE in patients with type 2 diabetes. It is still unclear what kinds of mechanisms are underlaying such abnormal N-glycosylation.

A group from Portuguese Institute of Oncology, etc. has reported that HOMER3 with sialyl-T and sialyl-Tn antigen could be a therapeutic target for bladder cancer (BC).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188679/

A total of 10 major glycans structures were identified for both BC cell lines: 5637 and T24, which present similar O-glycomes. Notably, both cell lines expressed high levels of mono- and di-sialylated T antigens (sialyl-T), also exhibiting neutral core 1 and sialylated and/or fucosylated core 2 structures

Based on glycomics analysis, samples were first enriched for membrane proteins by differential ultracentrifugation of whole cell protein extracts, digested with sialidase and enriched for T antigen expressing glycoproteins by PNA affinity pulldowns. The glycoproteins were identified by conventional bottom-up proteomics after trypsin digestion and analysis by nanoLC-CID-MS/MS. As a result, over 900 glycoproteins were identified as potentially expressing sialyl-T.

Among these, GLUT1(SLC2A1) and HOMER3 ranked first, suggesting potential for targeted therapeutics. GLUT1 is a pivotal membrane glucose transporter frequently overexpressed in more aggressive bladder tumours. HOMER3 has been implicated in neuronal signaling, T-cell activation and trafficking of beta amyloid peptides. HOMER3 at the cell membrane co-localizes in the same tumour area with sialyl-Tn and sialyl-T antigens in BC. According to immunohistochemistry, HOMER3 was diffusely expressed in wide tumour areas, both at the cytoplasm and cell membranes. These areas co-localized with very high sialyl-Tn and/or sialyl-T expressions areas.