Category Technology

A group from Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, China, etc. has reported on glycan profiling analysis of serum NRG1 in papillary thyroid cancer with using Lectin Microarrays.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8798758/

This study is evaluating if BRAF V600E mutant status in papillary thyroid cancer (PTC) patients could be detected by analyzing multiple glycan profiles of serum NRG1 through lectin microarray assays.

It has been reported that NRG1 overexpression was related in various cancers. NRG1 protein can bind to ERBB3 or ERBB4 protein, activating ERBB receptor tyrosine kinases, followed by the initiation of signal cascades, including PI3K/AKT pathways. NRG1 can be secreted to serum as reported.

lectin microarrays were used to analyze the different glycan profiles of NRG1 from sera of BRAF(+) PTC and BRAF wild type(-) PTC patients. Lectin microarray is a rapid and sensitive high-throughput technique to get glycan profiles, allowing researchers to directly analyze glycoproteins without liberation of glycans from the core substrate.

It was found that LEL, BPL and NML tended to have bound to NRG1 in BRAF(+) PTC patients compared to BRAF(-) controls.

A group from Department of Microbiology and Immunology, SUNY Upstate Medical University, Syracuse, NY USA, etc. has reported that H84T BanLec shows broad-spectrum antviral activities against Herpesvirus.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8803833/

As antivirals, one emerging strategy is the use of lectins to bind glycoproteins on the viral envelope. Naturally occurring lectins have been explored as broad-spectrum antimicrobials to inhibit viruses, bacteria, and other microbes. One promising lectin, BanLec, was derived from a banana lectin and shows high affinity to mannose N-glycans, and proved an effective strategy to combat HIV. Unfortunately, wild-type BanLec was a T-cell mitogen and activated basophils and mast cells. To address these issues, we developed H84T BanLec, replacing histidine at position 84 with threonine, which markedly reduced mitogenicity while maintaining the antiviral properties of the lectin.

High-mannose N-linked glycans are present on the envelope proteins of many viruses, including human herpesviruses. Human herpesviruses (HHVs) are enveloped DNA viruses that cause a variety of diseases, ranging from cold sores to skin rashes and infectious mononucleosis. HHVs cause lifelong infection, and after the initial infection, remain latent until reactivation. HHVs are prevalent worldwide, with up to 95% of the population infected with multiple types. Three of the most common HHVs are herpes simplex virus 1 (HSV-1), varicella-zoster virus (VZV), and human cytomegalovirus (HCMV).

The mechanism of action for H84T BanLec is virus dependent, and authors have found the following differences.
For VZV, H84T BanLec does not block attachment or entry. Instead, H84T BanLec interferes with post-entry steps in the viral replication process to prevent VZV spread, suggesting that H84T BanLec likely interacts with VZV-infected cells by inhibiting glycoprotein maturation, trafficking, virion assembly, or cell fusion.
For HCMV, H84T BanLec does not interfere with virion synthesis, but that the mechanism of action is through prevention of virus attachment and entry.
For HSV-1, H84T BanLec is also acting post-entry.

SI (selectivity index) calculated as CC₅₀/EC₅₀

A group from Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK, etc. has reported on neutralizing antibody responses against SARS-CoV-2 Omicron.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8723827/

Here is some presented data showing that the huge number of mutational changes present in Omicron lead to a substantial knockdown of neutralizing capacity of commercially available mAb.
“Commercial neutralizing antibody responses against SARS-CoV-2”

Degradation of neutralization titers of Omicron by sera from vaccines might be ineludible, but it is unlikely that vaccines will completely fail and it is hoped that although vaccine breakthroughs will occur, protection from severe disease will be maintained, perhaps by T cells. It is likely that the vaccine-induced T cell response to SARS-CoV-2 will be less affected than the antibody response.

A group from Gladstone Institutes, San Francisco, CA, USA, etc. has reported that infection with Omicron variant in unvaccinated individuals may not elicit effective cross-neutralizing antibodies against other variants. In vaccinated individuals, however, Omicron infection effectively induces immunity against itself and enhances protection against other variants.
https://www.medrxiv.org/content/10.1101/2022.01.13.22269243v1.full-text

To determine humoral immune responses induced by infection with the three different strains, sera from infected mice and tested their neutralization efficiency against SARS-CoV-2 strains were collected: WA1, Alpha, Beta, Delta, and Omicron. Efficient virus neutralization was defined by more than 50% reduction in plaque forming units at the lowest serum dilutions. Sera from Delta-infected mice showed the broadest cross-variant neutralization, effectively neutralizing all the strains except Beta. By contrast, while Omicron infection effectively neutralized Omicron itself, it exhibited limited (<50%) cross-neutralization of other strains. Sera from WA1-infected mice conferred effective protection against WA1, Alpha, and Delta, but not against Beta and Omicron. These results indicate limited immunity induced by Omicron relative to other strains, which may be due to its highly mutated spike protein or its lower replicative capacity. In human cases, interestingly, sera from vaccinated individuals with confirmed Omicron breakthrough infection showed the highest level of protection (>80%) against all strains, including Omicron as shown below.

A group from Key Laboratory of Biochemistry and Molecular Biology in University of Shandong Province, Weifang University, Weifang, China, etc. has reported Bacillus velezensis JC-K3 inoculation in wheat rhizosphere to improve salinity stress.
https://pubmed.ncbi.nlm.nih.gov/34987493/

Soil salinity is one of the main manifestations of global land degradation. At present, at least 20% of the cultivated land in the world is threatened by salinization to varying degrees.

In this study, a strain of endophytic Bacillus velezensis JC-K3 was isolated from wheat grown on saline soils. This strain not only showed strong salt tolerance and alkali resistance, but also produced IAA, siderophore, proline, soluble sugar, protease, cellulase, and glucanase, which have the potential to improve plant salt tolerance and induce systemic tolerance. Actually, comparing with the control group, inoculation with endophytic Bacillus velezensis JC-K3 increased the accumulation of wheat biomass (the plant height increased by 12.69%, the root length increased by 27.59%, the fresh weight of wheat shoot increased by 13.55%) under the tested salinity stress (Salt tolerance (12% NaCl, w/v) was tested on DF agar medium supplemented with 1-aminocyclopropane-1-carboxylate).

There was no significant difference in the content of endophytic bacteria in wheat roots after JC-K3 inoculation when compared with the control. The contents of Cyanobacteria in the shoots of wheat were significantly decreased after inoculation with JC-K3 (p ≤ 0.001), while the contents of Proteobacteria, Actinobacteria, Chloroflexi, Bacteroidetes, Firmicutes, Gemmatimonadetes, Nitrospirae, Saccharibacteria, and Parcubacteria were significantly increased (p ≤ 0.001). The contents of Actinobacteria, Chloroflexi, Acidobacteria, Gemmatimonadetes, and Nitrospirae in wheat leaves were significantly increased after inoculation with JC-K3 (p ≤ 0.001). The content of Parcubacteria in rhizosphere soil decreased significantly (p ≤ 0.05).

After inoculation with JC-K3, there was no significant difference in the content of endophytic fungi in wheat roots and leaves. The content of Glomeromycota in wheat shoots decreased significantly (p ≤ 0.05), the content of Ascomycota in rhizosphere soil of wheat decreased significantly, and the content of Basidiomycota and Rozellomycota increased significantly (p ≤ 0.05).

A group from The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA, etc. has reported a novel approach using glycoprotein targeted chimeric antigen receptor (CAR)-NK Cells for the treatment of SARS-CoV-2 infection.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8732772/

NK cells are innate lymphocytes of the immune system with an important role in the control of viral infections, and CAR-T and CAR-NK cells are emerging immunotherapies against cancer and infectious disease with great promise.

Typically, the expressed synthetic receptors on NK cells are designed to bind target surface protein. In this study, authors designed a CAR making use of a unique extracellular moiety (i.e., lectin) with binding properties dependent on target glycosylation. Targeting of glycoprotein, and specifically N-glycosylation products, with a CAR is rare. This is the first CAR targeting the N-glycans dispersed on SARS-CoV-2 Spike protein, and also, this would be the first lectin-based CAR designed and functionally tested in pre-clinical study.

As lectins have evolved over millions of years to be highly potent and selective to glycans, the H84T-BanLec CAR represents an entirely new approach in that it targets aberrant glycosylation patterns (high mannose, in this case) in SARS-CoV-2 viral proteins. Here, Banlec is a lectin which is known to have binding specificity to high mannose which exists in proximity to the receptor binding domain of the envelope SARS-CoV-2 Spike protein.

There is a strong need for the development of CARs with receptor targeting patterns that are less likely to be impacted by genomic point mutations observed in RNA virus such as SARS-CoV-2.