Galectins are not just β-galacside binding lectins, but have multifaceted functions

A group from Axe of Infectious and Immune Diseases, CHU de Quebec-Université Laval Research Centre, Faculty of Medicine, and Research Centre for Infectious Diseases, Laval University, Quebec, Canada etc. has reviewed about the multifaceted roles of galectins in self-defense.
https://www.sciencedirect.com/science/article/pii/S1044532324000642?via%3Dihub#bib63

Unlike other lectins, galectins lack signal peptides, so they are synthesized as soluble, non-glycosylated proteins in the cytosol, where glycan ligands are absent. Further, certain galectins, such as galectin-1 and galectin-3, have been found to translocate to the nucleus under specific conditions. This presents a paradox: galectins’ primary location is in the cytosol, an environment devoid of the glycans they bind.

Interestingly, however, galectins are also capable of reaching the extracellular space via a non-classical, leaderless secretory pathway.

This unique distribution of galectins both inside and outside the cell underscores their versatility, suggesting a layered regulatory mechanism that allows galectin function in host defense to be modulated both by their synthesis and by the spatial control of their access to ligands, extending their evolutionary role beyond traditional glycan recognition.

This must be one of the good reviews about Galectins.

A new lectin ALA might be effective on CCA treatments

A group from Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Thailand has reported about a new lectin ALA extracted from the seeds of Artocarpus lakoocha.
https://www.nature.com/articles/s41598-024-84444-7

ALA exhibits agglutinin activity and has binding specificity to T- and Tn-associated glycoproteins and monosaccharides such as Gal and GalNAc.

It was confirmed that glycans identified by ALA were elevated in human Cholangiocarcinoma (CCA) tissues.
ALA significantly reduced cell viability of CCA cells, KKU-100 and KKU-213B, in a dose-dependent manner (up to 30 µg/mL) with approximately a 30% decrease observed at the highest concentration. And also, ALA significantly reduced the migration and invasion ability of KKU-100 and KKU-213B cells in a dose-dependent manner with 1–2 µg/mL which did not affect cell viability.

These results suggest their therapeutic potential effects on CCA treatments.

Glycan binding specificity of marine lectins

A group from School of Medicine and Life Sciences, Far Eastern Federal University, Vladivostok, Russia has summarized about marine lectins and applicationn to human brain tumores.
https://pmc.ncbi.nlm.nih.gov/articles/PMC11679326/

HOL-18 from the marine sponge Halichondria okadai binds to complex N-glycans
OXYL from marine star Anneissia japonica binds to LacNAc type 2 but does not bind to LacNAc type 1
AVL from marine sponge Aphrocallistes vastus binds to sialylated-mucin glycans
ESA from the seaweed Eucheuma serra binds to high mannose N-glycans
UPL1 from the seaweed Ulva pertusa binds to GlcNAc and high-mannose glycans
BPL2 from the seaweed Bryopsis plumosa binds to trimannosyl core
KSL from red alga Kappaphycus striatus binds to high mannose N-glycans
DIFBL from the sea bass Dicentrarchus labrax binds to fucose
APL from starfish Asterina pectinifera binds to Tn antigen
CGL from the bivalve Crenomytilus grayanus binds to GalNAc/Gal and recognizes Gb3
MytiLec from the Mediterranean mussel also binds to Gb3
HCL from the marine sponge Haliclona cratera binds to binds to GalNAc/Gal
DTL from the ascidian Didemnum ternatanum binds to GlcNAc

A new glycobiomarker for discriminating Psoriatic Arthritis (PsA) and Rheumatoid Arthritis (RA)

A group from Division of Laboratory Diagnostics, Department of Laboratory Diagnostics, Faculty of Pharmacy, Wroclaw Medical University, Poland has reprted about a new glycobiomarker, change in glycosylation pattern of serum clusterin, for discriminating Psoriatic Arthritis (PsA) and Rheumatoid Arthritis (RA).
https://www.mdpi.com/1422-0067/25/23/13060

PsA and RA are connective tissue autoimmune diseases.
The present study aimed to check whether serum clusterin (CLU) concentration and its glycosylation pattern may be markers differentiating these diseases.

The followings were found.
Clusterin concentrations were significantly lower in the sera of the RA patients compared to the PsA group, and there were no other significant differences between the examined groups in CLU concentration.

The relative reactivities of CLU glycans with SNA (α2-6 Sia binding lectin) were significantly higher in the RA and PsA patients in comparison to the control group. There were no significant differences between the studied groups in the relative reactivities of CLU glycans with MAA (α2-3 Sia binding lectin).

These results indicate that PsA and RA can be distinguished by CLU concentration and sialic acid modification (by SNA).

β1-4 galactosylated glycan could inhibit SARS-CoV-2 infection

A group from Laboratory for Functional Glycomics, College of Life Sciences, Northwest University, Xi’an 710069, China has reported that β1-4 galactosylated glycan could inhibit SARS-CoV-2 infection.
https://www.sciencedirect.com/science/article/pii/S2090123224005666?via%3Dihub

It has been known that SARS-CoV-2-S protein has 22 potential N-glycosites and 17 O-glycosites, with 14 N-glycosites adorned with complex-type N-glycans, and ACE2 has a total of 7 N-glycosites, and most of these sites are occupied by complex-type N-glycans.

In this paper, it was demonstrated that the β1-4 galactosylated N-glycans of ACE2 play a crucial role as glycan receptors for the binding of S1 of SARS-CoV-2, and isolated glycoproteins harboring multivalent β1-4 galactosylated N-glycans exhibited the ability to competitively inhibit the interaction between S1 and ACE2, thereby preventing the attachment and entry of SARS-CoV-2 pseudovirus into host cells. This may be a rather late article, but let me introduce it to you.

Targeting Tn-antigen suppresses metastasis in breast Cancer

A group from Department of Gynecology and Obstetrics, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China, has reported that targeting Tn-antigen suppresses metastasis in breast Cancer.
https://onlinelibrary.wiley.com/doi/10.1111/jcmm.70279

Tn antigen was prevalent in breast carcinomas, particularly within metastatic lesions. Tn antigen expression was positively correlated with lymph node metastasis and poorer patient survival. Tn antigen-expressing breast cancer cells exhibited enhanced invasiveness and metastasis, along with significant activation of EMT and FAK signaling pathways.

There was a significant downregulation of E-cadherin and ZO-1, both of which are canonical epithelial markers, along with a significant up-regulation of the mesenchymal markers, including ZEB-1, Vimentin, Snail, and Slug in both cells expressing Tn antigen

Targeting Tn-positive cancer cells with HPA demonstrated the suppression of invasive and metastatic capabilities. It is known that the lectin HPA specifically recognizes and binds the Tn antigen, whereas the lectin PNA only recognizes and binds T antigen. Compared to the PNA-treated control group, mice in HPA-treated group exhibited a significantly reduced number of pulmonary metastases. In addition, immunofluorescence analysis showed that HPA treatment reduced formation of cellular protrusions of Tn-positive cancer cells, whereas PNA showed no inhibitory effects. At the molecular level, the EMT and FAK signaling pathways were consistently inhibited in Tn-positive cancer cells treated with HPA.

A new glycan marker for depressive disorder

A group from Division of Neuropsychiatry, Department of Neuroscience, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan has reported about a new glycan marker for predicting depressive disorder.
https://www.nature.com/articles/s41598-024-80507-x

It was found that plasma extracellular vesicles (EVs) containing WGA-binding von Willebrand factor (vWF) (WGA-vWF) could be a diagnostic marker for the diagnosis of patients with major depressive disorder (MDD) in a depressive state regardless of gender and age.

WGA-vWF expression was significantly lower in plasma EVs of patients with MDD in a depressive state than those of healthy control participants (HCs). ROC analysis indicated that the AUC value for the diagnosis was 0.92 (95% CI 0.82–1.00) between patients with MDD and HCs. Furthermore, WGA-vWF expression remarkably increased from depressive to remission processes. With using this result, it was possible to distinguish between patients with MDD in depressive and remission states (AUC of 0.98, 95% CI 0.93–1.00).

Bisecting GlcNAc could be an early Alzheimer’s disease biomarker

A group from Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Karolinska Institutet, Sweden has reported about a new glyca marker, bisecting GlcNAc, which is able to predict cognitive decline in amyloid- and tau-negative patients.
https://academic.oup.com/braincomms/article/6/6/fcae371/7826117?login=false

This is a reprt about an early biomarker for Alzheimer’s disease.

In Alzheimer’s disease, it has been known that an increased accumulation and aggregation of amyloid β-peptide (Aβ) causes amyloid formation in the brain followed by phosphorylation of tau and neurodegeneration and cognitive decline. In this study, it was found that Bisecting GlcNAc could be an early Alzheimer’s disease biomarker, which is able to predict cognitive decline already at an amyloid-/tau-negative stage.

SARS-CoV-2 antiviral activities using vegetable exosomes

A group from Nebraska Center for Virology, University of Nebraska-Lincoln, NE 68583, USA has reported about a new lectin found from shiitake exosomes.
https://www.mdpi.com/1999-4915/16/10/1546

Exosomes from fifteen local common vegetables were isolated by ultracentrifugation. These exosomes were evaluated for their antiviral activities against SARS-CoV-2 infection using an in vitro pseudovirus platform.
Their cytotoxicity using the standard MTT method indicated that all fifteen samples did not show significant cytotoxicity in a concentration of 1 × 10^10/mL exosomes. The antiviral activities of shiitake exosomes exhibited the lowest EC50 value 5.2 × 10^8/mL.
From the proteomic analysis of the exosomes, it was found that a lectin (named Shictin) of shiitake exosomes Contributed to the Antiviral Activities and exhibited strong activity against the SARS-CoV-2 Omicron variant with an IC50 value of 87 nM. It was also found that shictin is a C-type lectin and binds to GlcNAc.

Lectin staining is significantly different between formalin-fixed tissue samples and frozen tissue samples

A group from Department of Gastroenterological surgery, Gifu University School of Medicine, Gifu, Japan, has reported about differences in glycocalyx morphology and composition in frozen and formalin-fixed liver tumor sections.
https://www.sciencedirect.com/science/article/pii/S0344033824005715?via%3Dihub

It was found that surprisingly, there were many differences in lectin staining findings between frozen and formali-fixed tissue preparations, suggesting that FFPE processing affects lectin receptors, rendering frozen sections more reliable for accurate lectin staining.

From the lectin staining in frozen sections, the followings were found:
Normal hepatocytes showed strongly positive staining for PNA, RCA I, SBA, UEA I, GSL I, succinylated WGA, ECL, GSL II, STL, and VVL.
In contrast, hepatocellular carcinoma samples were strongly positive for DSL and GSL II.
Normal hepatocytes were positive for multiple GalNAc-related lectins (PNA, SBA, GSL I, and VVL), but these were not detected in hepatocellular carcinoma samples.

It was also found that DBA and UEA I staining were strongly positive in liver metastases from colorectal cancer and in melanoma liver metastases, ConA, WGA, succinylated WGA, and GSL II were strongly expressed.

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