Category Nature

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.

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).

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.

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 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).

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.

It is well-known that the 2024 Nobel Prize in Physics was awarded to two scientists who contributed to neural networks.
When I was working at Fujitsu, I read papers written by Prof. Shun-ichi Amari, a pioneer in neural networks, and I remembered that I was passionately discussing the possibilities of future computers with my colleagues, and I was surprised that Prof. Amari was not included as one of the recipients of the award. I felt very uncomfortable with it.
By the way, with the power of computers at that time, it was impossible to realize a neural network as software, so I and my colleagues were thinking about building it as hardware.

Prof. Amari’s pioneering researches:
1. A Theory of Adaptive Pattern Classifiers、1967
2. Characteristics of randomly connected threshold-element networks and network systems、1971
3. Learning Patterns and Pattern Sequences by Self-Organizing Nets of Threshold Elements、1972
4. Characteristics of Random Nets of Analog Neuron-Like Elements、1972